ﺑﺎﺯﮔﺸﺖ ﺑﻪ ﺻﻔﺤﻪ ﻗﺒﻠﯽ
خرید پکیج
تعداد آیتم قابل مشاهده باقیمانده : 3 مورد
نسخه الکترونیک
medimedia.ir

Heparin (unfractionated): Drug information

Heparin (unfractionated): Drug information
2024© UpToDate, Inc. and its affiliates and/or licensors. All Rights Reserved.
For additional information see "Heparin (unfractionated): Patient drug information" and "Heparin (unfractionated): Pediatric drug information"

For abbreviations, symbols, and age group definitions show table
Brand Names: Canada
  • Heparin Leo
Pharmacologic Category
  • Anticoagulant
Dosing: Adult

Dosage guidance:

Safety: Many concentrations of heparin are available ranging from 1 to 20,000 units/mL. Carefully examine each prefilled syringe or vial to ensure the correct concentration is selected.

Dosing: For weight-based IV heparin, an institution-specific dosing nomogram may help to achieve therapeutic anticoagulation more rapidly (see example based on aPTT under "Venous thromboembolism treatment"). If unusually large doses of heparin are required to achieve therapeutic targets, consider possible heparin resistance (Ref).

Antibiotic lock technique, adjunctive therapy

Antibiotic lock technique, adjunctive therapy (catheter-salvage strategy) (off-label use): Note: Antibiotic lock therapy is used in addition to systemic antibiotics for certain catheter-related infections when the catheter cannot be removed. Heparin is incompatible with ethanol and should not be used with ethanol lock therapy (Ref). Heparin is also incompatible with certain antibiotics; confirm compatibility prior to use (Ref).

Intracatheter: 100 to 5,000 units/mL in combination with an appropriate antibiotic. Heparin concentration depends on compatibility with the selected antibiotic, antibiotic concentration, and catheter type, which may vary by institution (Ref). For patients with end-stage renal disease requiring hemodialysis, maximum final heparin concentration should not exceed 1,000 units/mL due to increased risk of bleeding (Ref). Instill into each lumen of the catheter access port using a sufficient volume to fill the catheter (eg, 2 to 5 mL) with a maximum dwell time of ≤72 hours, depending on frequency of catheter use. Withdraw lock solution prior to catheter use; replace with fresh lock solution after catheter use (Ref).

Atrial fibrillation

Atrial fibrillation (to prevent stroke and systemic embolism): Note: When admitted for short-term hospitalization (eg, admission for a procedure or surgery), ambulatory patients taking an oral anticoagulant and not at high risk of immediate thromboembolism typically do not require bridging anticoagulation. Patients at high risk of thromboembolism (eg, recent cardioversion, high CHA2DS2-VASc score, prior cardioembolic stroke, current intracardiac thrombus) may be considered for bridging with a parenteral anticoagulant (see Transitioning between anticoagulants below) (Ref).

IV: Initial bolus of 60 to 80 units/kg (maximum: 5,000 units), followed by a continuous infusion of 12 to 18 units/kg/hour (maximum: 1,000 units/hour). Institutional dosing protocols may vary; adjust infusion rate to maintain anticoagulation target (Ref).

Frostbite

Frostbite (adjunctive agent) (off-label use): Note: Patients should be transferred to a facility that is familiar with managing patients with frostbite. Anticoagulation may be used in conjunction with thrombolytic therapy, either concurrently or following administration of the thrombolytic, but not as monotherapy (Ref). Optimal regimens, administration routes, and doses, including the use of therapeutic or low-dose anticoagulation after thrombolytic therapy, have not been identified; refer to institutional protocols.

Example regimens include:

When thrombolytic is administered IV:

IV: 500 to 1,000 units/hour as a fixed dose or targeted to an aPTT 2× control for up to 6 hours (Ref); some centers extend the duration to up to 5 days (Ref) or transition to therapeutic low-molecular-weight heparin (LMWH) (eg, enoxaparin) (Ref).

When thrombolytic is administered intra-arterial:

Intra-arterial: 500 units/hour administered through the intra-arterial catheter; targeted to a goal aPTT 50 to 70 seconds; after discontinuation of thrombolytic therapy, continue anticoagulation for 72 to 96 hours or transition to therapeutic LMWH (eg, enoxaparin) (Ref). Instead of intra-arterial heparin, some suggest the use of IV heparin after intra-arterial thrombolytic (see IV dosing above) (Ref).

Hemodialysis, anticoagulation of circuit

Hemodialysis, anticoagulation of circuit:

Note: Standard dosing has not been established for intermittent hemodialysis or CRRT. Recommendations provided below are example regimens. Refer to institutional protocols. May need to individualize dose based on patient-specific needs.

Intermittent hemodialysis:

Standard risk for bleeding:

IV: Initial: Bolus 1,000 units or 2,000 units at the beginning of hemodialysis, followed by a continuous infusion of 500 units/hour; stop the infusion 60 minutes before the end of hemodialysis (Ref).

If clotting occurs during first half of hemodialysis session: Increase IV bolus by 500 units before each subsequent session (eg, administer 1,500 units or 2,500 units, depending on the previously attempted dose, at the beginning of hemodialysis) until clotting no longer occurs or up to a maximum of 4,000 units; administer continuous infusion as described above (Ref).

If clotting occurs during second half of hemodialysis session: Administer the same IV bolus dose, but increase continuous infusion by 100 units/hour for each subsequent session (eg, administer 600 units/hour) until clotting no longer occurs or up to a maximum of 1,000 units/hour; stop the infusion 30 minutes before the end of hemodialysis (Ref).

High risk for bleeding:

Note: There is no standard practice to prevent clotting of the hemodialysis circuit among patients who are at high risk for bleeding. Dialysis without heparin is preferred, but may consider heparin anticoagulation in patients who continue to have recurrent filter thrombosis (Ref).

IV: Initial: Bolus 1,000 units at the beginning of hemodialysis; do not administer a continuous infusion during the procedure (Ref).

If clotting occurs during hemodialysis: IV: Bolus 1,000 units at the beginning of the subsequent hemodialysis session, followed by a continuous infusion of 500 units/hour; stop the infusion 60 minutes before the end of hemodialysis; if clotting continues, increase continuous infusion by 100 units/hour at each subsequent session (eg, administer 600 units/hour) until clotting no longer occurs or up to a maximum of 1,000 units/hour (Ref).

CRRT:

Note: For patients who require anticoagulation due to repeated clotting of hemofilter and when regional citrate anticoagulation is not feasible or unavailable (Ref).

IV: Initial: Bolus 500 to 1,000 units, followed by a continuous infusion of 500 units/hour; titrate to maintain an aPTT ~1.5 times the control or ~45 seconds (Ref).

Ischemic heart disease

Ischemic heart disease:

Acute coronary syndromes:

ST-elevation myocardial infarction (off-label use):

Adjunct to percutaneous coronary intervention: see Percutaneous coronary intervention for dosing guidance.

Adjunct to fibrinolysis: IV: Bolus 60 units/kg (maximum: 4,000 units), followed by 12 units/kg/hour (maximum: 1,000 units/hour); adjust infusion rate to maintain anticoagulation target based on institutional protocol; continue for ≥48 hours or until revascularization (if performed) (Ref).

No planned reperfusion: IV: Bolus 50 to 70 units/kg (maximum: 5,000 units), followed by 12 units/kg/hour; adjust infusion rate to maintain anticoagulation target based on institutional protocol; continue for ≥48 hours (Ref).

Non-ST-elevation acute coronary syndromes (off-label use):

Noninvasive, ischemia-guided approach: IV: Bolus 60 units/kg (maximum: 5,000 units), followed by 12 units/kg/hour (maximum: 1,000 units/hour); adjust infusion rate to maintain anticoagulation target based on institutional protocol; continue for ≥48 hours, until hospital discharge, or until management changes to an invasive strategy (eg, percutaneous coronary intervention [PCI]) (Ref).

Invasive approach (adjunct to percutaneous coronary intervention): see Percutaneous coronary intervention for dosing guidance.

Percutaneous coronary intervention (off-label use):

No prior anticoagulant therapy:

No planned glycoprotein IIb/IIIa inhibitor use: IV: Initial bolus of 70 to 100 units/kg (maximum: 10,000 units) to achieve activated clotting time (ACT) of 250 to 300 seconds (goal ACT may vary depending on point-of-care device); repeat bolus as needed to maintain goal ACT throughout procedure (Ref).

Planned glycoprotein IIb/IIIa inhibitor use: IV: Initial bolus of 50 to 70 units/kg (maximum: 7,000 units) to achieve ACT of 200 to 250 seconds (regardless of point-of-care device); repeat bolus as needed to maintain goal ACT throughout procedure (Ref).

Prior anticoagulant therapy:

Prior anticoagulation with heparin:

No planned glycoprotein IIb/IIIa inhibitor use: IV: Check ACT prior to PCI and administer heparin bolus as needed (eg, 2,000 to 5,000 units) to achieve ACT of 250 to 300 seconds (goal ACT may vary depending on point-of-care device); repeat bolus (maximum: 10,000 units) as needed to maintain goal ACT throughout procedure (Ref).

Planned glycoprotein IIb/IIIa inhibitor use: IV: Check ACT prior to PCI and administer heparin bolus as needed (eg, 2,000 to 5,000 units) to achieve ACT of 200 to 250 seconds (regardless of point-of-care device); repeat bolus (maximum 7,000 units) as needed to maintain goal ACT throughout procedure (Ref).

Prior anticoagulation with enoxaparin:

If percutaneous coronary intervention occurs ≤12 hours after the last SUBQ dose of enoxaparin: Transition to unfractionated heparin may not be preferred to reduce the risk of bleeding complications (Ref). Refer to Enoxaparin monograph for dosing recommendations.

If percutaneous coronary intervention occurs >12 hours after the last SUBQ dose of enoxaparin: May use unfractionated heparin; refer to recommendations above for PCI with no prior anticoagulant therapy (Ref).

Prior anticoagulation with fondaparinux:

No planned glycoprotein IIb/IIIa inhibitor use: IV: Initial bolus of 85 units/kg (maximum: 10,000 units) to achieve ACT of 250 to 300 seconds (goal ACT may vary depending on point-of-care device); repeat bolus as needed to maintain goal ACT throughout procedure (Ref).

Planned glycoprotein IIb/IIIa inhibitor use: IV: Initial bolus of 60 units/kg (maximum: 7,000 units) to achieve ACT of 200 to 250 seconds (regardless of point-of-care device); repeat bolus as needed to maintain goal ACT throughout procedure (Ref).

Mechanical heart valve, bridging anticoagulation

Mechanical heart valve, bridging anticoagulation (for interruptions in warfarin therapy) (off-label use): Note: Bridging during intervals of subtherapeutic anticoagulation should be considered for patients with mechanical mitral, tricuspid, or pulmonary valve replacement; however, for patients with mechanical aortic valve replacement, bridging is not required unless an additional thromboembolic risk factor is present or patient has an older-generation mechanical aortic valve (Ref).

IV: Limited data available: Initial: 18 units/kg/hour (no bolus) starting when INR falls below the therapeutic range; adjust infusion rate to maintain anticoagulation target based on institutional protocol. If patient is to undergo an invasive procedure, discontinue heparin 4 to 6 hours prior to procedure; reinitiate heparin infusion ≥24 hours after the procedure when bleeding risk is acceptable. Continue heparin until warfarin has been reinitiated and INR is within therapeutic range for 2 consecutive days (Ref).

Mechanical heart valve, postsurgical management

Mechanical heart valve, postsurgical management (to transition to warfarin) (off-label use): Note: Initiate postoperatively when risk of bleeding is acceptable (Ref).

IV: Limited data available: Initial: 12 to 18 units/kg/hour (no bolus); adjust infusion rate to maintain anticoagulation target based on institutional protocol. Overlap with warfarin until INR is stable and within therapeutic range for ≥2 consecutive days (Ref).

Peripheral arterial occlusion, acute

Peripheral arterial occlusion, acute (off-label use): Note: Specific dosing information is limited, but anticoagulation is commonly used at the time of diagnosis to limit thrombus propagation while the patient is evaluated for other possible interventions (Ref).

IV: Initial bolus of 60 to 80 units/kg, followed by an initial continuous infusion of 12 to 18 units/kg/hour; adjust infusion rate to maintain anticoagulation target based on institutional protocol (Ref).

Venous thromboembolism prophylaxis

Venous thromboembolism prophylaxis (alternative agent): Note: Low-weight patients (eg, <50 kg) may be more sensitive to routine prophylactic doses, increasing the potential for higher than intended levels of anticoagulation; consider adhering to every-12-hour dosing interval (Ref).

Medical patients with acute illness at moderate to high risk for venous thromboembolism: SUBQ: 5,000 units every 8 to 12 hours; continue for length of hospitalization or until fully ambulatory (Ref); extended prophylaxis beyond acute hospital stay is not routinely recommended (Ref).

Nonorthopedic surgery:

Patients with active cancer:

SUBQ: 5,000 units 2 to 4 hours prior to surgery, then 5,000 units every 8 hours thereafter (Ref) or 5,000 units every 8 to 12 hours started ~6 to 24 hours after surgery (Ref). Note: The optimal duration of prophylaxis has not been established, but it is usually given for a minimum of 7 to 10 days; extending for up to 4 weeks may be reasonable in those undergoing major abdominal or pelvic surgery (Ref).

Patients without cancer: Note: For patients with moderate or high risk of venous thromboembolism (VTE) and low risk of bleeding.

SUBQ: 5,000 units every 8 to 12 hours, with initial dose given ≥2 hours prior to surgery. Alternatively, may postpone pharmacologic prophylaxis until after surgery (eg, high bleeding risk) when it is safe to initiate. Continue until fully ambulatory and risk of VTE has diminished (typically up to 10 days) (Ref).

Orthopedic surgery (eg, hip fracture surgery, total hip arthroplasty, total knee arthroplasty): SUBQ: 5,000 units every 8 to 12 hours, with initial dose administered ≥12 hours preoperatively or ≥12 hours postoperatively once hemostasis is achieved; optimal duration of prophylaxis is unknown, but it is usually given for a minimum of 10 to 14 days and can be extended for up to 35 days; some experts suggest a duration in the lower end of the range (10 to 14 days) for total knee arthroplasty or higher end of the range (~30 days) for total hip arthroplasty (Ref). For extended duration of prophylaxis, may transition to an oral anticoagulant or alternative SUBQ anticoagulant with less frequent dosing (Ref).

Pregnancy: Note: Dose intensity is individualized based on risk of thrombosis and bleeding complications (Ref).

Prophylactic dose (also referred to as intermediate dose to account for weight gain during pregnancy):

First trimester: SUBQ: 5,000 to 7,500 units every 12 hours (Ref).

Second trimester: SUBQ: 7,500 to 10,000 units every 12 hours (Ref).

Third trimester: SUBQ: 10,000 units every 12 hours (reduce dose if the aPTT becomes elevated) (Ref).

Adjusted dose (therapeutic): Note: For patients at the highest risk of developing VTE (eg, history of recurrent thrombosis, severe thrombophilia), especially those who are receiving long-term therapy with an oral anticoagulant prior to pregnancy (Ref).

SUBQ: 10,000 units every 12 hours; adjust dose to target an aPTT of 1.5 to 2.5 times control, measured 6 hours after injection; monitor aPTT once daily until stable and within therapeutic range, then monitor every 1 to 2 weeks (Ref).

Management around labor and delivery:

Prior to delivery: Discontinue heparin at the onset of spontaneous labor. Prior to planned induction of labor or cesarean delivery, discontinue heparin ≥12 hours before in patients receiving 7,500 to 10,000 units every 12 hours or ≥24 hours before in patients receiving >10,000 units/dose, >20,000 units/day, or an adjusted therapeutic dose. Consider checking coagulation parameters before delivery. Appropriate discontinuation is particularly important if neuraxial anesthesia is planned (Ref).

Postpartum : In patients at high risk of VTE who require an adjusted therapeutic dose, may restart ≥4 to 6 hours after vaginal delivery or ≥6 to 12 hours after cesarean delivery unless significant bleeding occurred or traumatic neuraxial catheter placement. For patients who require lower VTE prophylaxis doses (eg, patients not receiving an adjusted therapeutic dose during pregnancy) or those without an acute VTE, restart prophylaxis 6 to 12 hours after vaginal delivery and 12 to 24 hours after cesarean delivery (Ref). Anticoagulation should continue for up to 6 weeks postpartum, but potentially longer (Ref).

Venous thromboembolism treatment, deep vein thrombosis and/or pulmonary embolism

Venous thromboembolism treatment, deep vein thrombosis and/or pulmonary embolism: Note: IV heparin may be preferred for initial therapy in patients who are hemodynamically unstable, may need invasive procedures or thrombolysis due to extensive clot burden, are obese, have renal failure, or when rapid reversal of anticoagulation may be needed (Ref). If thrombolytics are used, it is recommended to discontinue heparin during administration then resume upon completion of the thrombolytic infusion (Ref).

Inpatient treatment: IV: Initial: 80 units/kg bolus followed by a continuous infusion of 18 units/kg/hour or 5,000 unit bolus followed by 1,333 units/hour; adjust infusion rate to maintain target laboratory values based on institutional protocol (Ref). Note: Weight-based dosing is more effective than fixed dosing at reaching therapeutic anticoagulation (Ref).

Example Weight-Based IV Heparin Nomogram for Treatment of Venous Thromboembolisma,b

aHull 2022a

bThis is one example of a weight-based heparin dosing nomogram. Each institution should establish their own heparin dosing nomogram. Other heparin nomograms based on aPTT or anti-Factor Xa monitoring may be employed. Therapeutic range for aPTT must be established at each individual laboratory (Dager 2018).

cUse actual body weight for calculations.

Initial dose and monitoring

80 units/kg bolus (maximum dose: 10,000 units)c, then 18 units/kg/hour (maximum initial infusion: 2,000 units/hour)c

Obtain aPTT 6 hours after initial heparin bolus

Dosing adjustments and monitoring

If using anti-Factor Xa activity (units/mL)

Response

If using aPTT (seconds)

0 to 0.09

• Bolus 25 units/kg

• Increase infusion by 3 units/kg/hour

• Repeat assay in 6 hours

<40

0.1 to 0.19

• Increase infusion by 2 units/kg/hour

• Repeat assay in 6 hours

40 to 49

0.2 to 0.29

• Increase infusion by 1 unit/kg/hour

• Repeat assay in 6 hours

50 to 69

0.3 to 0.7

• No change (within therapeutic range)

• Repeat assay in 6 hours

• Once therapeutic for 2 consecutive assays, may change to once-daily assays

70 to 110

0.71 to 0.79

• Decrease infusion by 1 unit/kg/hour

• Repeat assay in 6 hours

111 to 120

0.8 to 0.89

• Stop infusion for 1 hour, then decrease by 2 units/kg/hour

• Repeat assay 6 hours after restarting the infusion

121 to 130

0.9 to 0.99

• Stop infusion for 1 hour, then decrease by 3 units/kg/hour

• Repeat assay 6 hours after restarting the infusion

131 to 140

1 to 1.09

• Stop infusion for 2 hours, then decrease by 4 units/kg/hour

• Repeat assay 6 hours after restarting the infusion

141 to 150

≥1.1

• Stop infusion for 2 hours, then decrease by 5 units/kg/hour and notify clinician

• Repeat assay 6 hours after restarting the infusion

>150

Outpatient treatment: Note: Alternative for patients who have a contraindication to other anticoagulants.

SUBQ: Initial: 333 units/kg, followed by 250 units/kg every 12 hours (Ref).

Pregnancy (therapeutic, adjusted dose):

SUBQ: Initial: 10,000 units every 12 hours; adjust dose to target an aPTT of 1.5 to 2.5 times control, measured 6 hours after injection; monitor aPTT once daily until stable and within therapeutic range, then monitor every 1 to 2 weeks (Ref).

Management around labor and delivery:

Prior to delivery: Discontinue heparin at the onset of spontaneous labor. Prior to planned induction of labor or cesarean delivery, discontinue heparin ≥24 hours before in patients receiving a therapeutic adjusted dose of heparin. Consider checking coagulation parameters before delivery. Appropriate discontinuation is particularly important if neuraxial anesthesia is planned (Ref).

Postpartum: May restart ≥4 to 6 hours after vaginal delivery or ≥6 to 12 hours after cesarean delivery, unless significant bleeding occurred or traumatic neuraxial catheter placement. Optimal duration of anticoagulation is unknown. In general, total duration of anticoagulation (antepartum plus postpartum) should be at least 3 to 6 months with at least 6 weeks postpartum (Ref).

Transitioning between anticoagulants: Note: This provides general guidance on transitioning between anticoagulants; also refer to local protocol for additional detail.

Transitioning from another anticoagulant to IV heparin:

Transitioning from a therapeutic dose of SUBQ low-molecular-weight heparin or SUBQ fondaparinux to a therapeutic dose of IV heparin: Start IV heparin without a bolus dose (infusion rate depends on the indication) 1 to 2 hours before the next dose of low-molecular-weight heparin (LMWH) or fondaparinux would have been due (Ref).

Transitioning from warfarin to a therapeutic dose of IV heparin: Stop warfarin and, when INR is as close as possible to the lower end of the targeted INR range, start IV heparin without a bolus dose (infusion rate depends on the indication) (Ref).

Transitioning from a direct-acting oral anticoagulant to a therapeutic dose of IV heparin: Stop direct-acting oral anticoagulant (DOAC) and, when the next DOAC dose would have been due, start IV heparin without a bolus dose (infusion rate depends on the indication) (Ref).

Transitioning from IV heparin to another anticoagulant:

Transitioning from a therapeutic dose of IV heparin to therapeutic SUBQ low-molecular-weight heparin or SUBQ fondaparinux: Stop IV heparin and within 1 hour start SUBQ LMWH or SUBQ fondaparinux. Note: If aPTT is not within therapeutic range at the time heparin is stopped, consult local protocol (Ref).

Transitioning from a therapeutic dose of IV heparin to warfarin: Start warfarin and continue IV heparin until INR is within therapeutic range (Dager 2018; Hull 2022a). Note: Overlap IV heparin with warfarin until INR is ≥2 for at least 2 measurements taken ~24 hours apart (duration of overlap is ~5 days) (Ref).

Transitioning from a therapeutic dose of IV heparin to a direct-acting oral anticoagulant: Start DOAC when the heparin infusion is stopped (consult local protocol if the aPTT is above the target range) (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.

Altered kidney function: IV, SUBQ: Mild to severe impairment: No initial dosage adjustment necessary; adjust to maintain anticoagulation target based on institutional protocol (Ref).

Renal replacement therapies: Poorly dialyzed (Ref): IV, SUBQ: No supplemental dose or initial dosage adjustment necessary in patients receiving renal replacement therapies (eg, hemodialysis, peritoneal dialysis, CRRT, PIRRT); adjust to maintain anticoagulation target based on institutional protocol (Ref).

Dosing: Hepatic Impairment: Adult

No dosage adjustment required; adjust therapeutic heparin according to aPTT or anti-Factor Xa activity.

Dosing: Obesity: Adult

The recommendations for dosing in patients with obesity are based upon the best available evidence and clinical expertise. Senior Editorial Team: Jeffrey F. Barletta, PharmD, FCCM; Manjunath P. Pai, PharmD, FCP; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC.

Venous thromboembolism prophylaxis:

Class 1, 2, or 3 obesity (BMI ≥30 kg/m2):

SUBQ: 5,000 to 7,500 units every 8 hours (Ref). Note: Until large prospective studies are available evaluating dosing and outcomes, it is reasonable to use 5,000 units every 8 hours. In patients with a BMI >50 kg/m2, consider 7,500 units every 8 hours (Ref).

Therapeutic anticoagulation, treatment:

Class 1 or 2 obesity (BMI 30 to 39 kg/m2):

IV: Use actual body weight for dosing calculation; adjust infusion rate to maintain target laboratory values based on institutional protocol (Ref). Refer to indication-specific dosing recommendations.

Class 3 obesity (BMI ≥40 kg/m2):

IV: Use adjusted body weight for dosing calculation; adjust infusion rate to maintain target laboratory values based on institutional protocol (Ref). Alternatively, dosing based on actual body weight (with or without a bolus) may be considered with an initial reduced maintenance dose (eg, 12 units/kg/hour for VTE treatment) (Ref). Refer to indication-specific dosing recommendations.

Rationale for recommendations:

Heparin is extensively bound to plasma proteins and has a low Vd, which is similar to blood volume. However, increased blood volume is expected with increasing body weight, resulting in increased dosing requirements for patients with obesity (Ref).

Venous thromboembolism prophylaxis: Due to increases in blood volume and likely decreased bioavailability of SUBQ heparin in patients with obesity, higher dosing (7,500 units every 8 hours) has been recommended in those who require venous thromboembolism prophylaxis (Ref). However, a large retrospective cohort study suggests similar occurrence of venous thromboembolism and major bleeding in patients without obesity and those with obesity (BMI ≥30 kg/m2) when administered prophylactic unfractionated heparin at 5,000 units every 8 hours (Ref). Data are lacking in patients with a BMI >50 kg/m2.

Therapeutic anticoagulation, treatment: Retrospective studies show no difference in time to achievement of therapeutic aPTT or bleeding rates when actual body weight was used for bolus and maintenance treatment dosing without dose capping in the following weight classifications: BMI <30 kg/m2, BMI 30 to 39.9 kg/m2, or BMI ≥40 kg/m2 (Ref). In patients with a BMI ≥40 kg/m2, a retrospective study using actual body weight for weight-based dosing showed higher likelihood of supratherapeutic aPTT values compared to patients with a BMI <40 kg/m2 (Ref).

Dosing: Adjustment for Toxicity: Adult

Heparin-induced thrombocytopenia: Immediately discontinue all heparin therapy and exposures (eg, heparin flushes and heparin-coated catheters) for intermediate probability or high probability heparin-induced thrombocytopenia or heparin-induced thrombocytopenia with thrombosis based on the 4T score; switch to an alternative nonheparin anticoagulant (Ref).

Dosing: Older Adult

Patients >60 years of age may have higher serum levels and clinical response (longer aPTTs) as compared to younger patients receiving similar dosages. Lower dosages may be required.

Dosing: Pediatric

(For additional information see "Heparin (unfractionated): Pediatric drug information")

Dosage guidance:

Safety: Many concentrations of heparin are available and range from 1 to 20,000 units/mL. Carefully examine each prefilled syringe, bag, or vial prior to use to ensure that the correct concentration is chosen. Heparin lock flush solution is intended only to maintain patency of IV devices and is not to be used for anticoagulant therapy.

Central line flush, patency

Central line flush, patency (intermittent doses): Limited data available (Ref): Infants, Children, and Adolescents: When using intermittent flushes of heparin to maintain patency of single and double lumen central catheters, various recommendations exist; refer to institution-specific protocols. Capped polyvinyl chloride catheters and peripheral heparin locks require flushing more frequently (eg, every 6 to 8 hours). Volume of heparin flush is usually similar to volume of catheter (or slightly greater). Dose of heparin flush used should not approach therapeutic unit per kg dose. Additional flushes should be given when stagnant blood is observed in catheter, after catheter is used for drug or blood administration, and after blood withdrawal from catheter.

Congenital heart defect palliated with systemic to pulmonary artery shunts or with high-risk central venous lines, thromboprophylaxis

Congenital heart defect palliated with systemic to pulmonary artery shunts (eg, Sano shunt, Blalock-Taussig shunt, central shunt) or with high-risk central venous lines (eg, previous thrombosis or hypercoagulable states), thromboprophylaxis: Infants, Children, and Adolescents: Low Dose: Continuous IV infusion: 10 to 15 units/kg/hour (Ref).

Extracorporeal membrane oxygenation, anticoagulation

Extracorporeal membrane oxygenation (ECMO) (venoarterial [VA]/cardiac), anticoagulation:

Note: While used to prevent thrombosis, full anticoagulation dosing is necessary.

Infants, Children, and Adolescents: IV: 100 units/kg prior to ECMO cannulation followed by continuous IV heparin infusion to maintain the activated clotting time (ACT) between 180 and 220 seconds; ACT should be checked hourly while patient is on ECMO; additional monitoring targets for heparin therapy are prolongation of the PTT to 1.5 to 2.5 times the control value or an anti-Xa level of 0.3 to 0.7 units/mL (Ref).

Parenteral nutrition additive, venous access patency

Parenteral nutrition (PN) additive, venous access patency: Infants, Children, and Adolescents: 1 unit/mL (final heparin concentration in PN), both central and peripheral. The final concentration of heparin used for PN solutions may need to be decreased to 0.5 units/mL in small infants receiving larger PN volumes in order to avoid approaching therapeutic amounts (Ref).

Peripheral arterial catheters in situ, thromboprophylaxis

Peripheral arterial catheters in situ, thromboprophylaxis: Infants, Children, and Adolescents: Intra-arterial (via arterial catheter): Continuous infusion of heparin at a final concentration of 5 units/mL at 1 mL/hour (Ref).

Thrombosis, treatment

Thrombosis, treatment:

Systemic heparinization:

Infants: IV: Initial loading dose: 75 units/kg over 10 minutes; then initial continuous maintenance infusion at 28 units/kg/hour; adjust dose to maintain an anti-Xa activity of 0.35 to 0.7 units/mL or an aPTT range that correlates to this anti-Xa range or a protamine titration range of 0.2 to 0.4 units/mL (Ref).

Children and Adolescents: IV: Initial loading dose: 75 units/kg over 10 minutes, then initial continuous maintenance infusion at 20 units/kg/hour; adjust dose to maintain an anti-Xa activity of 0.35 to 0.7 units/mL or an aPTT range that correlates to this anti-Xa range or a protamine titration range of 0.2 to 0.4 units/mL (Ref). Note: A lower initial continuous maintenance infusion dose of 18 units/kg/hour in older patients has also been suggested (Ref).

Note: Because of variation among hospitals with reagents (lot numbers) and corresponding control of aPTT values, individual institutions should establish unique, institution-specific nomograms based on current reagent. Due to extensive variability within reagents and anti-Xa levels with corresponding aPTTs, a specific nomogram has not been provided; refer to guidelines for a specific nomogram (Ref).

Systemic to pulmonary artery shunt thrombosis (eg, Sano shunt, Blalock-Taussig shunt, central shunt); treatment in patients with congenital heart disease (CHD): Infants, Children, and Adolescents: IV: Bolus: 50 to 100 units/kg, ongoing continuous infusion should be considered (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Pediatric

All patients: No dosage adjustment required; adjust therapeutic heparin according to aPTT or anti-Xa activity

Dosing: Hepatic Impairment: Pediatric

All patients: No dosage adjustment required; adjust therapeutic heparin according to aPTT or anti-Xa activity

Adverse Reactions (Significant): Considerations
Major bleeding

Heparin increases the risk of bleeding (hemorrhage), including major bleeding. Bleeding may occur at any site and may be severe enough to be life-threatening, with reports of fatal cases (eg, intracranial bleeding) (Ref). Bleeding is reversible with the use of protamine.

Mechanism: Dose-related; binds to antithrombin III, increasing its activity 1,000-fold (Ref). This complex inactivates factors IIa (thrombin), Xa, IXa, XIa, and XIIa, leading to decreased coagulation (Ref).

Onset: Varied; may occur at any time but data show that it is more common toward the end of planned therapy (Ref). Bleeding may occur sooner; however, this is largely driven by other risk factors for bleeding that are present (Ref).

Risk factors:

• Supratherapeutic dosing (excess bolus or infusion) or aPTT level (Ref)

• Kidney impairment (Ref)

• Uncontrolled and severe hypertension

• History of hemorrhagic stroke

• Recent gastrointestinal bleed

• Females

• Age >60 years

• Concurrent antiplatelet therapy (eg, P2Y12 inhibitors, GPIIb/IIIa inhibitors) (Ref)

• Concurrent use of thrombolytics (Ref)

• Liver disease with impaired hemostasis

• Ulcerative GI lesions

• Continuous GI tube drainage

• Subacute bacterial endocarditis

• Concurrent coagulation disorders (Ref)

• Patients with hereditary antithrombin III deficiency receiving concurrent antithrombin III therapy

• Recent brain, spinal, or ophthalmic surgery

• Recent surgery, trauma, or invasive procedures (Ref)

• Spinal interventions, including epidurals or spinal taps (Ref)

Osteoporosis

Studies primarily in patients who are pregnant show that heparin may cause significant decreased bone mineral density (BMD) ≥10% decrease from baseline femur measurements (Ref). A study in patients on hemodialysis showed decreases in BMD primarily in the lumbar spine (Ref). BMD losses may still be significant 6 months after discontinuation (Ref). Bone fractures are uncommon (Ref).

Mechanism: Dose- and time-related (Ref); binds to osteoprotegerin, sterically inhibiting its interaction with RANKL on osteoblasts. This promotes RANK-RANKL linkages, activating osteoclasts and causing bone resorption (Ref).

Onset: Delayed; occurs after about 3 to 6 months (Ref).

Risk factors:

• High doses (15,000 to 30,000 units/day), but this is controversial (Ref)

• Long-term use of at least 3 to 6 months (Ref)

• Use of unfractionated heparin (versus low-molecular weight heparin) (Ref)

• Pregnancy (Ref)

Thrombocytopenia

Mild thrombocytopenia may occur during therapy (Ref). Heparin-induced thrombocytopenia without thrombosis (HIT) or with thrombosis (HITT) may also occur, warranting discontinuation of therapy, and can be fatal without treatment (Ref). HIT/HITT should be suspected if there is a 30% to 50% reduction in platelet count from baseline with or without new thrombosis formation while on heparin therapy (Ref). The 4T score can be used to evaluate the probability of HIT and whether to further pursue laboratory evaluation (Ref). HIT/HITT antibodies resolve approximately 90 to 100 days after discontinuation of therapy; however, it is unknown if those with a history of HIT/HITT are more likely to develop the reaction again if re-exposed to heparin. Therefore, avoidance of heparin is recommended (or allowance of only short-term use for specific indications) even after resolution of antibodies (Ref).

Mechanism: Time-related; HIT is an immune-mediated complication where IgG antibodies directed at complexes of heparin and the platelet protein, platelet factor 4 (PF4), bind to the FcγIIa receptors on platelets (Ref). This causes platelet activation, aggregation, and significant thrombin generation, leading to thrombosis (Ref). Thrombocytopenia is secondary to the significant activation and usage of platelets, effectively removing them from circulation (Ref).

Onset: Varied; the decrease in platelet count typically occurs 5 to 10 days after heparin initiation; however, platelet count can fall within 24 hours after heparin initiation in “rapid-onset HIT,” which tends to occur in individuals with circulating heparin antibodies secondary to a recent exposure (Ref). “Delayed-onset HIT” is also possible, which occurs when platelet count fall occurs weeks after heparin is discontinued (Ref). Thrombosis can precede thrombocytopenia in up to 25% of cases (Ref).

Risk factors for HIT:

• Longer courses of heparin (Ref)

• Use of unfractionated heparin (versus low molecular weight heparin) (Ref)

• Bovine heparin (Ref)

• Patients undergoing surgery (particularly cardiac and orthopedic surgery) (Ref)

• Patients presenting with major trauma (Ref)

• Females (Ref)

Additional risk factors for HITT:

• High antibody levels (optical density or titer) (Ref)

• Marked thrombocytopenia (>90% decline from baseline) (Ref)

Adverse Reactions

The following adverse drug reactions are derived from product labeling unless otherwise specified.

Postmarketing:

Cardiovascular: Cardiac tamponade (Su 2005), vasospasm

Dermatologic: Transient alopecia

Endocrine & metabolic: Hyperkalemia (Su 2005), suppression of aldosterone synthesis

Genitourinary: Priapism (Burke 1983)

Hematologic & oncologic: Hemorrhage (including adrenal hemorrhage, ovarian hemorrhage, retroperitoneal hemorrhage) (Krishnaswamy 2011), heparin-induced thrombocytopenia, thrombocytopenia, thrombosis in heparin-induced thrombocytopenia (including acute myocardial infarction, cerebral thrombosis, cerebrovascular accident, deep vein thrombosis, mesenteric thrombosis, peripheral gangrene, pulmonary embolism, renal artery thrombosis, skin necrosis)

Hepatic: Increased serum alanine aminotransferase, increased serum aspartate aminotransferase

Hypersensitivity: Anaphylactic shock (Bottio 2003), hypersensitivity reaction (including pruritus and burning sensation of feet [plantar side]), infusion-related reaction (skin necrosis), nonimmune anaphylaxis

Local: Erythema at injection site (SUBQ), hematoma at injection site (SUBQ), irritation at injection site (SUBQ), pain at injection site (SUBQ), skin ulceration at injection site (SUBQ), tissue necrosis at injection site (SUBQ)

Neuromuscular & skeletal: Bone fracture (Barbour 1994), decreased bone mineral density (Douketis 1996), osteoporosis (with long-term use) (Casele 2006)

Contraindications

Hypersensitivity to heparin or any component of the formulation (unless a life-threatening situation necessitates use and use of an alternative anticoagulant is not possible); severe thrombocytopenia; history of heparin-induced thrombocytopenia; history of heparin-induced thrombocytopenia with thrombosis; uncontrolled active bleeding (except when this is due to disseminated intravascular coagulation); not for use when appropriate blood coagulation tests cannot be obtained at appropriate intervals (applies to full-dose heparin only).

Note: Some products contain benzyl alcohol as a preservative; their use in neonates, infants, or pregnant or breastfeeding patients is contraindicated by some manufacturers.

Warnings/Precautions

Concerns related to adverse effects:

• Heparin resistance: Dose requirements >35,000 units/24 hours to maintain a therapeutic aPTT may occur in patients with antithrombin deficiency, increased heparin clearance, elevations in heparin-binding proteins, and elevations in factor VIII and/or fibrinogen; frequently encountered in patients with fever, thrombosis, thrombophlebitis, infections with thrombosing tendencies, myocardial infarction, cancer, and in postsurgical patients; measurement of anticoagulant effects using anti-Factor Xa levels may be of benefit.

• Hepatic effects: Elevations in serum aminotransferases have been observed during therapy. These elevations should be evaluated with caution as they may occur and resolve in the setting of the underlying condition for which heparin is being used.

• Hypersensitivity reactions: Hypersensitivity reactions, including fever, chills, urticaria, asthma, rhinitis, lacrimation, and anaphylaxis, have been reported. In patients with a documented hypersensitivity reaction, heparin should only be considered in life-threatening situations when use of an alternative anticoagulant is not possible. Some products are derived from animal tissue and may be contraindicated in patients with animal allergies (ie, pork); consult individual prescribing information.

Dosage form specific issues:

• Benzyl alcohol and derivatives: Some dosage forms may contain benzyl alcohol as a preservative. In neonates, large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity ("gasping syndrome"); the "gasping syndrome" consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol with caution in neonates. See manufacturer's labeling. Use in neonates, infants, or pregnant or nursing mothers is contraindicated by some manufacturers; the use of preservative-free heparin is, therefore, recommended in these populations.

• Sulfites: Some preparations contain sulfite which may cause allergic reactions.

Other warnings/precautions:

• Fatal medications errors: Many concentrations of heparin are available ranging from 1 unit/mL to 20,000 units/mL. Clinicians must carefully examine each prefilled syringe or vial prior to use ensuring that the correct concentration is chosen; fatal hemorrhages have occurred related to heparin overdose especially in pediatric patients.

Warnings: Additional Pediatric Considerations

Confirm the concentration of all heparin injection vials prior to administration; do not use heparin injection as a "catheter lock flush" as the injection is supplied in various concentrations including highly concentrated strengths. Fatal hemorrhages have occurred in pediatric patients when higher concentrations of heparin injection were confused with lower concentrations of heparin lock flush.

Heparin-induced thrombocytopenia (HIT) has been reported in pediatric patients; incidence and risk factors are not well-defined due to variability related to patient inclusion and laboratory techniques; incidence rates up to 2.3% in PICU patients have been reported, and cases observed at both low and high levels of heparin exposure (eg, venous access device line flushes and supratherapeutic doses associated with hemodialysis and during cardiopulmonary bypass). Monitor platelet count closely; if HIT develops, consider alternate anticoagulation therapy (eg, danaparoid, argatroban) (ACCP [Monagle 2012]).

Heparin resistance should be suspected in pediatric patients if unable to achieve an activated clotting time (ACT) >300 seconds after administration of >600 units/kg (ACCP [Giglia 2013]).

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Intravenous:

Generic: 2000 units (1000 mL); 25,000 units (500 mL); 2000 units in 0.9% NaCl per liter (1000 mL); 25,000 units/500 mL (500 mL); 25,000 units/500 mL in NaCl 0.45% (500 mL)

Solution, Intravenous [preservative free]:

Generic: 2000 units in 0.9% NaCl per liter (1000 mL); 25,000 units/500 mL in NaCl 0.45% (500 mL)

Solution, Injection, as sodium:

Generic: 1000 units/mL (1 mL, 10 mL, 30 mL); 5000 units/mL (1 mL, 10 mL); 5000 units/0.5 mL (0.5 mL); 10,000 units/mL (1 mL, 4 mL, 5 mL); 20,000 units/mL (1 mL)

Solution, Injection, as sodium [preservative free]:

Generic: 1000 units/mL (2 mL); 5000 units/mL (1 mL); 5000 units/0.5 mL (0.5 mL)

Solution, Intravenous, as sodium:

Generic: 1000 units (500 mL); 10,000 units (250 mL [DSC]); 12,500 units (250 mL [DSC]); 20,000 units (500 mL); 25,000 units (250 mL); 1 units/mL (1 mL, 2 mL, 2.5 mL, 3 mL, 5 mL, 10 mL); 10 units/mL (1 mL, 3 mL [DSC], 5 mL, 10 mL); 100 units/mL (1 mL, 2 mL, 2.5 mL, 3 mL, 5 mL, 10 mL); 1000 units/500 mL in NaCl 0.9% (500 mL); 12,500 units/250 mL in NaCl 0.45% (250 mL); 25,000 units/250 mL in Dextrose 5% (250 mL); 25,000 units/250 mL in NaCl 0.45% (250 mL)

Solution, Intravenous, as sodium [preservative free]:

Generic: 10 units/mL (1 mL, 2 mL, 2.5 mL, 3 mL, 5 mL, 10 mL); 100 units/mL (3 mL [DSC], 5 mL [DSC]); 25,000 units/250 mL in Dextrose 5% (250 mL)

Solution Prefilled Syringe, Injection, as sodium [preservative free]:

Generic: 5000 units/0.5 mL (0.5 mL)

Generic Equivalent Available: US

Yes

Pricing: US

Solution (Heparin (Porcine) in NaCl Intravenous)

1000UT/500ML 0.9% (per mL): $0.01

2000UNIT/L 0.9% (per mL): $0.01

12500UT/250ML 0.45% (per mL): $0.06

25000UT/250ML 0.45% (per mL): $0.05 - $0.07

25000UT/500ML 0.45% (per mL): $0.02 - $0.03

Solution (Heparin Na (Pork) Lock Flsh PF Intravenous)

1 units/mL (per mL): $1.16 - $1.25

10 units/mL (per mL): $1.00 - $1.10

100 units/mL (per mL): $1.03 - $1.13

Solution (Heparin Sod (Porcine) in D5W Intravenous)

40UNIT/ML 5% (per mL): $0.03

100 units/mL (per mL): $0.05 - $0.07

25000UT/500ML 5% (per mL): $0.03 - $0.04

Solution (Heparin Sod (Pork) Lock Flush Intravenous)

10 units/mL (per mL): $0.13

100 units/mL (per mL): $0.19 - $0.50

Solution (Heparin Sodium (Porcine) Injection)

1000 units/mL (per mL): $0.26 - $0.91

5000 units/mL (per mL): $1.16 - $5.40

10000 units/mL (per mL): $2.52 - $9.16

20000 units/mL (per mL): $12.00 - $20.95

Solution (Heparin Sodium (Porcine) PF Injection)

1000 units/mL (per mL): $5.70 - $8.24

5000 units/0.5 mL (per 0.5 mL): $2.64 - $7.20

5000 units/mL (per mL): $7.20

Solution Prefilled Syringe (Heparin Sodium (Porcine) Injection)

5000 units/0.5 mL (per 0.5 mL): $3.72 - $3.72

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous:

Generic: 25,000 units/500 mL (500 mL)

Solution, Injection, as sodium:

Generic: 1000 units/mL (1 mL, 2 mL, 10 mL, 30 mL); 10,000 units/mL (0.5 mL, 1 mL, 5 mL); 1000 units (500 mL, 1000 mL)

Solution, Intravenous, as sodium:

Generic: 20,000 units/500 mL in Dextrose 5% (500 mL); 100 units/mL (2 mL, 10 mL); 25,000 units/250 mL in Dextrose 5% (250 mL)

Solution Prefilled Syringe, Subcutaneous:

Generic: 5000 units/0.5 mL (0.5 mL)

Administration: Adult

SUBQ: Inject in subcutaneous tissue only (not muscle tissue). Injection sites should be rotated (usually left and right portions of the abdomen, above iliac crest).

IM: Do not administer IM due to pain, irritation, and hematoma formation.

Continuous IV infusion: Infuse via infusion pump. If preparing solution, mix thoroughly prior to administration.

Catheter patency: Practice is variable. If used for this purpose, refer to institution-specific protocols. The intention is only to maintain patency of IV catheters and is not to be used for anticoagulant therapy.

Intravesical (off-label use): Various dosage regimens of heparin (20,000 to 50,000 units) alone or with alkalinized lidocaine (1% to 4%) have been instilled into the bladder.

Intra-arterial (off-label use): Infuse via infusion pump. If preparing solution, mix thoroughly prior to administration (Ref).

Administration: Pediatric

Note: Many concentrations of heparin are available and range from 1 to 20,000 units/mL. Carefully examine each prefilled syringe, bag, or vial prior to use to ensure that the correct concentration is chosen.

Parenteral: Do not administer IM due to pain, irritation, and hematoma formation.

IV:

IV bolus: Administered over 10 minutes (Ref).

Continuous IV infusion: Infuse via infusion pump.

Heparin lock: Inject via injection cap using positive pressure flushing technique. Heparin lock flush solution is intended only to maintain patency of IV devices and is not to be used for anticoagulant therapy.

Central venous catheters: Must be flushed with heparin solution when newly inserted, daily (at the time of tubing change), after blood withdrawal or transfusion, and after an intermittent infusion through an injectable cap.

SubQ: Not all preparation intended for SubQ administration, verify product selection. Inject in subcutaneous tissue only (not muscle tissue). Injection sites should be rotated (usually left and right portions of the abdomen, above iliac crest).

Usual Infusion Concentrations: Adult

Note: Premixed solutions available

IV infusion: 25,000 units in 250 mL (concentration: 100 units/mL) of D5W, 1/2NS, or NS

Usual Infusion Concentrations: Pediatric

Note: Premixed solutions available

IV infusion: 100 units/mL

Use: Labeled Indications

Anticoagulation: Prophylaxis and/or treatment of thromboembolic disorders (eg, venous thromboembolism, pulmonary embolism) and thromboembolic complications associated with atrial fibrillation or other disease states; prevention of clotting in arterial and cardiac surgery; as an anticoagulant for blood transfusions, extracorporeal circulation, and dialysis procedures.

Note: Heparin lock flush solution and certain premixed infusion bags (eg, 2 units/mL) are intended only to maintain patency of IV devices and are not to be used for systemic anticoagulant therapy.

Use: Off-Label: Adult

Antibiotic lock technique, adjunctive therapy (catheter-salvage strategy); Frostbite; Mechanical heart valve, bridging anticoagulation (for interruptions in warfarin therapy); Mechanical heart valve, postsurgical management (to transition to warfarin); Non-ST-elevation acute coronary syndromes; Percutaneous coronary intervention; Peripheral arterial occlusion, acute; ST-elevation myocardial infarction

Medication Safety Issues
Sound-alike/look-alike issues:

Heparin may be confused with Hespan

High alert medication:

The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (anticoagulants, parenteral and oral) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).

National Patient Safety Goals:

The Joint Commission (TJC) requires healthcare organizations that provide anticoagulant therapy to have approved protocols and evidence-based practice guidelines in place to reduce the risk of anticoagulant-associated patient harm. Patients receiving anticoagulants should receive individualized care through a defined process that includes medication selection, dosing (including adjustments for age, renal function, or liver function), drug-drug interactions, drug-food interactions, other applicable risk factors, monitoring, patient and family education, proper administration, reversal of anticoagulation, management of bleeding events, and perioperative management. This does not apply to routine short-term use of anticoagulants for prevention of venous thromboembolism during procedures or hospitalizations (NPSG.03.05.01).

Older Adult: High-Risk Medication:

Heparin is identified in the Screening Tool of Older Person's Prescriptions (STOPP) criteria as a potentially inappropriate medication in older adults (≥65 years of age) with a history of gastric antral vascular ectasia (O’Mahony 2023).

Administration issues:

The 100 unit/mL concentration should not be used to flush heparin locks, IV lines, or intra-arterial lines in neonates or infants <10 kg (systemic anticoagulation may occur). The 10 unit/mL flush concentration may inadvertently cause systemic anticoagulation in infants <1 kg who receive frequent flushes.

Other safety concerns:

Heparin sodium injection 10,000 units/mL and Hep-Lock U/P 10 units/mL have been confused with each other. Fatal medication errors have occurred between the two whose labels are both blue. Never rely on color as a sole indicator to differentiate product identity.

Heparin lock flush solution is intended only to maintain patency of IV devices and is not to be used for anticoagulant therapy.

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.

Acalabrutinib: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the anticoagulant effect of Heparin. Management: Decrease the dose of heparin or agents with antiplatelet properties if coadministration is required. Risk D: Consider therapy modification

Alemtuzumab: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Alteplase: May enhance the anticoagulant effect of Anticoagulants. Risk X: Avoid combination

Anacaulase: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Anagrelide: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Andexanet Alfa (Coagulation Factor Xa [Recombinant], Inactivated): May diminish the therapeutic effect of Heparin. Risk X: Avoid combination

Angiotensin II Receptor Blockers: Heparin may enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Risk C: Monitor therapy

Angiotensin-Converting Enzyme Inhibitors: Heparin may enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Antithrombin: May enhance the anticoagulant effect of Heparin. Risk C: Monitor therapy

Apixaban: May enhance the anticoagulant effect of Anticoagulants. Refer to separate drug interaction content and to full drug monograph content regarding use of apixaban with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods. Risk X: Avoid combination

Bromperidol: May enhance the adverse/toxic effect of Anticoagulants. Risk C: Monitor therapy

Caplacizumab: May enhance the anticoagulant effect of Anticoagulants. Management: Avoid coadministration of caplacizumab with antiplatelets if possible. If coadministration is required, monitor closely for signs and symptoms of bleeding. Interrupt use of caplacizumab if clinically significant bleeding occurs. Risk D: Consider therapy modification

Collagenase (Systemic): Anticoagulants may enhance the adverse/toxic effect of Collagenase (Systemic). Specifically, the risk of injection site bruising and/or bleeding may be increased. Risk C: Monitor therapy

Corticorelin: Heparin may enhance the adverse/toxic effect of Corticorelin. Significant hypotension and bradycardia have been previously attributed to this combination. Risk X: Avoid combination

Dabigatran Etexilate: May enhance the anticoagulant effect of Anticoagulants. Refer to separate drug interaction content and to full drug monograph content regarding use of dabigatran etexilate with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods. Risk X: Avoid combination

Dasatinib: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Deferasirox: Anticoagulants may enhance the adverse/toxic effect of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased. Risk C: Monitor therapy

Defibrotide: May enhance the anticoagulant effect of Anticoagulants. Risk X: Avoid combination

Deoxycholic Acid: Anticoagulants may enhance the adverse/toxic effect of Deoxycholic Acid. Specifically, the risk for bleeding or bruising in the treatment area may be increased. Risk C: Monitor therapy

Desirudin: Anticoagulants may enhance the anticoagulant effect of Desirudin. Management: Discontinue treatment with other anticoagulants prior to desirudin initiation. If concomitant use cannot be avoided, monitor patients receiving these combinations closely for clinical and laboratory evidence of excessive anticoagulation. Risk D: Consider therapy modification

Dipyridamole: May enhance the adverse/toxic effect of Heparin. Specifically, the risk of bleeding may be increased. Management: Use caution and reduce the dose of heparin or dipyridamole if these agents are combined. Risk D: Consider therapy modification

Drospirenone-Containing Products: May enhance the hyperkalemic effect of Heparin. Risk C: Monitor therapy

Edoxaban: May enhance the anticoagulant effect of Anticoagulants. Refer to separate drug interaction content and to full drug monograph content regarding use of edoxaban with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods. Management: Some limited combined use may be indicated during periods of transition from one anticoagulant to another. See the full edoxaban drug monograph for specific recommendations on switching anticoagulant treatment. Risk X: Avoid combination

Eplerenone: Heparin may enhance the hyperkalemic effect of Eplerenone. Risk C: Monitor therapy

Factor X (Human): Anticoagulants (Inhibitors of Factor Xa) may diminish the therapeutic effect of Factor X (Human). Risk C: Monitor therapy

Hemin: May enhance the anticoagulant effect of Anticoagulants. Risk X: Avoid combination

Herbal Products with Anticoagulant/Antiplatelet Effects (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Anticoagulants. Bleeding may occur. Risk C: Monitor therapy

Ibritumomab Tiuxetan: Anticoagulants may enhance the adverse/toxic effect of Ibritumomab Tiuxetan. Both agents may contribute to an increased risk of bleeding. Risk C: Monitor therapy

Ibrutinib: May enhance the adverse/toxic effect of Anticoagulants. Risk C: Monitor therapy

Icosapent Ethyl: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Inotersen: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Kanamycin: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Landiolol: Heparin may enhance the hypotensive effect of Landiolol. Heparin may decrease the serum concentration of Landiolol. Risk C: Monitor therapy

Lecanemab: May enhance the adverse/toxic effect of Anticoagulants. Specifically, the risk of hemorrhage may be increased. Risk C: Monitor therapy

Levothyroxine: Heparin may decrease the serum concentration of Levothyroxine. Risk C: Monitor therapy

Limaprost: May enhance the adverse/toxic effect of Anticoagulants. The risk for bleeding may be increased. Risk C: Monitor therapy

Lipid Emulsion (Fish Oil Based): May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Mesoglycan: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

MiFEPRIStone: May enhance the adverse/toxic effect of Anticoagulants. Specifically, the risk of bleeding may be increased. Risk X: Avoid combination

Nintedanib: Anticoagulants may enhance the adverse/toxic effect of Nintedanib. Specifically, the risk for bleeding may be increased. Risk C: Monitor therapy

Nitroglycerin: May diminish the anticoagulant effect of Heparin. Nitroglycerin may decrease the serum concentration of Heparin. Risk C: Monitor therapy

Nonsteroidal Anti-Inflammatory Agents: May enhance the anticoagulant effect of Heparin. Management: Decrease the dose of heparin or nonsteroidal anti-inflammatory agents (NSAIDs) if coadministration is required. Risk D: Consider therapy modification

Nonsteroidal Anti-Inflammatory Agents (Ophthalmic): May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Nonsteroidal Anti-Inflammatory Agents (Topical): May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Obinutuzumab: Anticoagulants may enhance the adverse/toxic effect of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased. Risk C: Monitor therapy

Omacetaxine: Anticoagulants may enhance the adverse/toxic effect of Omacetaxine. Specifically, the risk for bleeding-related events may be increased. Management: Avoid concurrent use of anticoagulants with omacetaxine in patients with a platelet count of less than 50,000/uL. Risk X: Avoid combination

Omega-3 Fatty Acids: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Oritavancin: May diminish the therapeutic effect of Heparin. Specifically, oritavancin may artificially increase the results of laboratory tests commonly used to monitor IV heparin effectiveness, which could lead to incorrect decisions to decrease heparin doses. Risk X: Avoid combination

Palifermin: Heparin may increase the serum concentration of Palifermin. Management: If heparin is used to maintain an intravenous line, rinse the line with saline prior to and after palifermin administration. Risk C: Monitor therapy

Pentosan Polysulfate Sodium: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Pentoxifylline: May enhance the anticoagulant effect of Heparin. Risk C: Monitor therapy

Pirtobrutinib: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Potassium Salts: Heparin may enhance the hyperkalemic effect of Potassium Salts. Risk C: Monitor therapy

Potassium-Sparing Diuretics: Heparin may enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy

Prostacyclin Analogues: May enhance the adverse/toxic effect of Anticoagulants. Specifically, the antiplatelet effects of these agents may lead to an increased risk of bleeding with the combination. Risk C: Monitor therapy

Protein C Concentrate (Human): May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Reteplase: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Rivaroxaban: Anticoagulants may enhance the anticoagulant effect of Rivaroxaban. Refer to separate drug interaction content and to full drug monograph content regarding use of rivaroxaban with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods. Risk X: Avoid combination

Salicylates: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Streptokinase: May enhance the anticoagulant effect of Anticoagulants. Risk X: Avoid combination

Sugammadex: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Sulodexide: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Telavancin: May diminish the therapeutic effect of Heparin. Specifically, telavancin may artificially increase the results of laboratory tests commonly used to monitor IV heparin effectiveness, which could lead to incorrect decisions to decrease heparin doses. Risk X: Avoid combination

Tenecteplase: May enhance the anticoagulant effect of Anticoagulants. Risk X: Avoid combination

Tibolone: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Tipranavir: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Tobacco (Smoked): May decrease the serum concentration of Heparin. Risk C: Monitor therapy

Urokinase: May enhance the anticoagulant effect of Anticoagulants. Management: Consider avoiding this combination due to an increased risk of hemorrhage. If anticoagulants are coadministered with urokinase, monitor patients closely for signs and symptoms of bleeding. Risk D: Consider therapy modification

Vitamin E (Systemic): May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Vitamin K Antagonists (eg, warfarin): Anticoagulants may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Volanesorsen: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Vorapaxar: May enhance the adverse/toxic effect of Anticoagulants. More specifically, this combination is expected to increase the risk of bleeding. Risk X: Avoid combination

Zanubrutinib: May enhance the adverse/toxic effect of Anticoagulants. Risk C: Monitor therapy

Pregnancy Considerations

Heparin does not cross the placenta (ESC [Regitz-Zagrosek 2018]).

Due to pregnancy-induced physiologic changes, the risk of thromboembolism is increased during pregnancy and the immediate postpartum period. Heparin may be used for anticoagulation in pregnancy (ACOG 2018). Due to a better safety profile and ease of administration, the use of low molecular weight heparin (LMWH) is generally preferred over heparin (unfractionated heparin [UFH]) in pregnancy (ACOG 2018; Bates 2018; ESC [Regitz-Zagrosek 2018]); however, heparin may be preferred in pregnant patients with kidney dysfunction (Bates 2018). Anticoagulant therapy for the prevention and treatment of thromboembolism in pregnant patients can be discontinued prior to induction of labor or a planned cesarean delivery (Bates 2018) or LMWH can be converted to UFH in higher risk patients (ESC [Regitz-Zagrosek 2018]). Consult current recommendations for appropriate use in pregnancy.

Patients with mechanical heart valves have an increased risk of adverse maternal and fetal outcomes and these risks are greater without appropriate anticoagulation. UFH or LMWH may be used in pregnant patients with mechanical heart valves. Increased monitoring is required to maintain adequate therapeutic concentrations during pregnancy (consult current recommendations for details) (ESC [Regitz-Zagrosek 2018]; ACC/AHA [Otto 2021]).

Some products contain benzyl alcohol as a preservative; their use in pregnant patients is contraindicated by some manufacturers; use of a preservative-free formulation is recommended.

Breastfeeding Considerations

Heparin is not present in breast milk (Bates 2018).

Heparin is considered acceptable for use in patients who are breastfeeding (Bates 2018; ESC [Regitz-Zagrosek 2018]). However, some products contain benzyl alcohol as a preservative; their use in breastfeeding patients is contraindicated by some manufacturers due to the association of gasping syndrome in premature infants.

Monitoring Parameters

Hemoglobin, hematocrit, platelet count, PT, aPTT, signs/symptoms of bleeding, risk factors for bleeding, fecal occult blood test (if clinically indicated); potassium.

Level of anticoagulation can be monitored by anti-Factor Xa activity or aPTT (calibrated by anti-Factor Xa activity or by protamine titration assay) or activated clotting time depending upon the indication (ACCP [Garcia 2012]; ACCP [You 2012]; Bates 2001; Hirsh 1994; Vandiver 2012).

Patients with antiphospholipid syndrome may have a prolonged aPTT at baseline due to effects of the antiphospholipid antibodies. In order to prevent a prolonged value from being mistaken for therapeutic anticoagulation, aPTT should be measured at baseline. In this situation, anti-Factor Xa monitoring may be preferred (Hull 2019a).

Platelet count should be routinely monitored to assess for risk of heparin-induced thrombocytopenia (HIT). If the patient experienced HIT within the past 100 days after receiving heparin or low-molecular-weight heparin, risk of recurrence is higher. Monitor closely if pre-exposure history is uncertain (ACCP [Guyatt 2012]).

Reference Range

Adult:

Treatment of venous thromboembolism and atrial fibrillation:

IV administration:

Anti-Factor Xa activity: 0.3 to 0.7 unit/mL.

Protamine titration: 0.2 to 0.4 unit/mL.

aPTT: Therapeutic range must be established in individual laboratories to target an aPTT prolongation that corresponds to anti-Factor Xa activity or protamine titration values (ACCP [Garcia 2012]; ACCP [You 2012]; Bates 2001; Hirsh 1994; Vandiver 2012).

SUBQ administration:

Anti-Factor Xa activity: 0.3 to 0.7 unit/mL or equivalent aPTT, obtained 6 to 8 hours after injection (ACOG 2018; Dager 2018).

ST-elevation myocardial infarction as adjunct to fibrinolysis or when no reperfusion is planned: aPTT of 1.5 to 2 times control (or an aPTT of ~50 to 70 seconds) is recommended (ACCF/AHA [O’Gara 2013]; Lincoff 2020). Note: An anti-Factor Xa target has not been established for this indication.

Non-ST-elevation acute coronary syndrome: aPTT of 1.5 to 2 times control (or an aPTT of ~50 to 70 seconds) is recommended (ACCF/AHA [Amsterdam 2014]; Cutlip 2024). Note: An anti-Factor Xa target has not been established for this indication.

Postmechanical heart valve replacement surgery (to transition to warfarin therapy): Some experts recommend an aPTT of 1.5 to 2 times control when bleeding risk is acceptable postoperatively and heparin is initiated (ACCP [Douketis 2022]). Note: An anti-Factor Xa target has not been established for this indication.

Mechanism of Action

Potentiates the action of antithrombin III and thereby inactivates thrombin (as well as other coagulation factors IXa, Xa, XIa, XIIa, and plasmin) and prevents the conversion of fibrinogen to fibrin; heparin also stimulates release of lipoprotein lipase (lipoprotein lipase hydrolyzes triglycerides to glycerol and free fatty acids)

Pharmacokinetics (Adult Data Unless Noted)

Note: Increased interpatient variability of pharmacokinetic parameters in pediatric patients compared to adults; however, age-related decreases in volume of distribution and clearance with increasing pediatric patient age have been reported (ACCP [Monagle 2012]; McDonald 1981).

Onset of action: Anticoagulation: IV: Immediate; SUBQ: ~20 to 30 minutes.

Absorption: Oral, rectal: Erratic at best from these routes of administration; SUBQ absorption is also erratic, but considered acceptable for prophylactic use.

Distribution:

Premature neonates (data based on single dose of 100 units/kg within 4 hours of birth) (McDonald 1981): Inversely proportional to gestational age (GA).

GA 25 to 28 weeks: 81 ± 41 mL/kg.

GA 29 to 32 weeks: 73.3 ± 24.8 mL/kg.

GA 33 to 36 weeks: 57.8 ± 32.2 mL/kg.

Adults: Following a single 75 unit/kg dose: 36.6 ± 7.4 mL/kg (McDonald 1981).

Metabolism: Complex; thought to occur by depolymerization and desulphation via the reticuloendothelial system primarily in the liver and spleen (ACCP [Garcia 2012]; Dawes 1979; Estes 1980; Kandrotas 1992).

Half-life elimination:

Age-related: Shorter half-life reported in premature neonates compared to adult patients.

Premature neonates GA 25 to 36 weeks (data based on single dose of 100 units/kg within 4 hours of birth): Mean range: 35.5 to 41.6 minutes (McDonald 1981).

Dose-dependent: IV bolus: 25 units/kg: 30 minutes (Bjornsson 1982); 100 units/kg: 60 minutes (de Swart 1982); 400 units/kg: 150 minutes (Olsson 1963).

Mean: 1.5 hours; Range: 1 to 2 hours; affected by obesity, renal function, malignancy, presence of pulmonary embolism, and infections.

Note: At therapeutic doses, elimination occurs rapidly via nonrenal mechanisms. With very high doses, renal elimination may play more of a role; however, dosage adjustment remains unnecessary for patients with renal impairment (Kandrotas 1992).

Excretion: Urine (small amounts as unchanged drug); Note: At therapeutic doses, elimination occurs rapidly via nonrenal mechanisms. With very high doses, renal elimination may play more of a role; however, dosage adjustment remains unnecessary for patients with renal impairment (Kandrotas 1992).

Clearance: Age-related changes; within neonatal population, slower clearance with lower GA; however, when compared to adults, the overall clearance in neonatal and pediatric patients is faster than adults (ACCP [Monagle 2012 ]; McDonald 1981).

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

Altered kidney function: The half-life may be increased.

Hepatic function impairment: The half-life may be increased or decreased.

Older adult: Plasma levels may be higher.

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AE) United Arab Emirates: Heparin leo | Hikma heparin | Liquemin | Multiparin;
  • (AR) Argentina: Heparina | Heparina duncan | Heparina gemepe | Heparina sodica | Riveparin-heparina rivero | Sobrius | Sodiparin;
  • (AT) Austria: Heparin gilvasan | Heparin immuno | Ivorat anti-xa | Liquemin;
  • (AU) Australia: Heparin | Heparin sodium chloride | Heparinised Saline;
  • (BD) Bangladesh: Heparin | Heparon;
  • (BE) Belgium: Calparine | Heparine | Heparine leo | Heparine natrium b.braun | Heparine novo-nordisk | Liquemine;
  • (BF) Burkina Faso: Heparine medis | Sakarin 25000;
  • (BG) Bulgaria: Heparin | Heparin na;
  • (BR) Brazil: Actparin | Cellparin | Hepamax s | Heparin | Heparina sodica | Heptar | Liquemine | Parinex;
  • (CH) Switzerland: Calciparine | Heparin | Heparin bichsel | Heparin fresenius | Heparin kabi | Heparin na | Heparin novonordisk | Heparin sintetica | Heparine choay | Liquemin;
  • (CI) Côte d'Ivoire: Pan heparine | Sakarin 25000;
  • (CL) Chile: Heparina;
  • (CN) China: Heparin sod.;
  • (CO) Colombia: Hepamax s | Heparina | Heparina northia | Heparina sodica | Inhepar | Liquemine;
  • (DE) Germany: Calciparin | Calciparine | Calcium Heparin Sanofi-Aventis | Heparin | Heparin Natrium | Heparin-calcium | Liquemin | Liquemin n | Thrombophob | Vetren;
  • (DO) Dominican Republic: Hepagel | Heparina;
  • (EC) Ecuador: Hepamax s | Hepanir | Heparina | Heparina sodica | Inhepar | Nuparin | Sobrius;
  • (EE) Estonia: Calciparin | Heparin | Heparin sodium rovi | Heparin wzf | Vasparin;
  • (ES) Spain: Calciparina choay | Heparina leo | Heparina sodica chiesi | Heparina sodica pan quim | Heparina sodica rovi;
  • (ET) Ethiopia: Heparin;
  • (FI) Finland: Hepaflex | Heparin | Heparin leo | Thromboliquine;
  • (FR) France: Calciparine | Heparine Calcium | Heparine calcium dakota | Heparine calcium panpharma | Heparine roche | Heparine Sodium | Heparine Sodium Panpharma | Heparine sodium roche | Prontoprime;
  • (GB) United Kingdom: Calciparine | Heparin | Heparin boots | Heparin ca | Heparin ebl | Heparin immuno | Heparin na | Heparin pain/byrne | Heparin sodium rovi | Heparin weddel | Minihep | Minihep calcium | Pump-hep | Trav heparin | Uniparin;
  • (GR) Greece: Calciparine | Heparin | Heparin bichsel | Heplok;
  • (HK) Hong Kong: Heparin | Heparin novo | Heparinized saline;
  • (HR) Croatia: Heparin Belupo;
  • (ID) Indonesia: Hepagusan | Heparin | Heparin Sodium B Braun | Inviclot;
  • (IE) Ireland: Calciparine | Heparin | Heparin na | Heplok | Minihep | Minihep calcium | Multiparin;
  • (IL) Israel: Heparin;
  • (IN) India: Caprin | Cath-flush | Celhep | Celparin | Declot | Hep | Hep lock | Hepaglan | Heparen | Heparin | Hethin f | Keparin | Lofh | Lomorin | Neporin | Reniparin | Rinhepa | Thinla | Thiparin h | Thromboparin | Troyhep | V-parin;
  • (IT) Italy: Calciparina | Croneparina | Ecafast | Ecasolv | Emoklar | Eparical | Eparina | Eparina calcica merck generics | Eparina calcica ratiopharm | Eparina calcica sandoz | Eparina novo | Eparina roberts | Eparina squibb | Eparina vister | Eparinger | Eparinlider | Eparven | Epsoclar | Eudipar | Flusolv | Heparinum | Liquemin | Normoparin | Pharepa | Reoflus | Sosefluss | Trombolisin | Zepac;
  • (JO) Jordan: Heparin;
  • (JP) Japan: Caprocin | Deribadex | Hepacarin | Hepafilled | Hepaflush | Heparin calcium ajinomoto | Heparin lente novo | Heparin mochida | Heparin na | Heparin na lock | Heparin organon | Heparin pf novo | Heparin pfizer | Heparin sodium ajinomoto | Heparin sodium fujo | Heparin sodium fuso | Heparin sodium mitsubishi | Heparin sodium mochida | Heparin sodium n | Heparin sodium n ay | Heparin sodium sankyo | Novo Heparin | Novo heparin aventis | Panheprin | Pemiroc;
  • (KE) Kenya: Beparine | Bruhep | Celparin | Hepa | Heparen | Heparin indar | Heparin sodium fresenius | Heparine | Heparinol | Heparovit h | Medihep | Racil;
  • (KR) Korea, Republic of: Bm heparin sodium | Calciparin | Gcc heparin sodium | Hanlim heparin sodium | Heparin | Heparin na | Huons heparin sodium | Huparin | Jw heparin | Jw heparin sodium | K heparin | Pain | Pine;
  • (KW) Kuwait: Heparin leo;
  • (LB) Lebanon: Heparine | Heparine medis | Pharepa;
  • (LT) Lithuania: Calcium heparin | Heparin Natrium | Heparin panpharma | Heparin sanofi | Heparin sodica b. braun | Heparin sodium panpharma | Heparina sodica b braun | Heparinum wzf | Nevparin;
  • (LU) Luxembourg: Calparine | Heparine | Liquemine;
  • (LV) Latvia: Calcium heparin | Heparin | Heparin Natrium | Heparinum wzf | Nevparin;
  • (MA) Morocco: Calciparine | Heparine sodique roche | Liquemine;
  • (MX) Mexico: Dixaparine | Hep-tec | Heparina | Heparina gi pisa | Inhepar | Proparin | Rimbipar;
  • (MY) Malaysia: Eprin | Heparin | Heparinol | Unihepa | Vaxcel heparin sodium;
  • (NG) Nigeria: Heparin;
  • (NL) Netherlands: Calparine | Heparine;
  • (NO) Norway: Hepaflex | Heparin | Heparin campus | Heparin gilvasan | Heparin leo | Heparin panpharma | Monoparin | Nycoheparin | Pump-hep;
  • (NZ) New Zealand: Heparin | Monoparin | Multiparin;
  • (PE) Peru: Heparina Sodic | Heparina sodica | Paripharm | Sobrius;
  • (PH) Philippines: Britton heparin na | Bruhep | Cenprahep | Dega Heparin sodium (bovine) | Hemastat | Heparin | Hepasino | Hepastal | Heprin | Kabihep | Nuparin | Sakarin 25000;
  • (PK) Pakistan: Ecafast | Heparin | Pine inj. | Vaxcel heparin sodium;
  • (PL) Poland: Calciparine | Coaparin | Heparin | Heparinum | Heparinum wzf;
  • (PR) Puerto Rico: Hep lock | Heparin | Heparin lock flush | Heparin sodium;
  • (PT) Portugal: Heparina choay | Heparina sodica b braun | Heparina sodica rovi | Heparina zentiva;
  • (PY) Paraguay: Actparin | Heparina leo | Heparina sodica fada pharma | Heparina sodica fusa | Heparina sodica prosalud | Rhoneparina sodica | Sobrius;
  • (QA) Qatar: Heparin Leo;
  • (RO) Romania: Heparin belmed;
  • (RU) Russian Federation: Heparin | Heparin sandoz | Heparin sodium braun;
  • (SA) Saudi Arabia: Heparin | Hikma heparin | Multiparin | Vaxcel heparin sodium;
  • (SE) Sweden: Heparin | Heparin Fermenta | Heparin leo;
  • (SG) Singapore: Heparin;
  • (SI) Slovenia: Heparin | Heparin gilvasan;
  • (SK) Slovakia: Heparin;
  • (TH) Thailand: Hepamax s | Heparin | Heparin dbl | Nuparin;
  • (TN) Tunisia: Calciparine | Cutheparine | Heparine | Heparine choay | Heparine medis;
  • (TR) Turkey: Biemparin | Calciparine | Heparine Sodium | Heparinum | Heparx | Hexarin | Koparin | Liquemine | Poliparin | Seloparin | Vasparin;
  • (TW) Taiwan: Agglutex | Cutheparine | Hepac | Hepac lock flush | Heparin | Heparin sodium fresenius | Hesharin | Pine | Sodium heparin;
  • (UA) Ukraine: Gizende | Heparin;
  • (UG) Uganda: Hepanir;
  • (UY) Uruguay: Heparina | Heparina calcica | Heparina northia | Heparina sodica | Rhoneparina sodica | Riveparin;
  • (VE) Venezuela, Bolivarian Republic of: Heparina | Heparina sodica;
  • (VN) Viet Nam: Henalip | Wellparin;
  • (ZA) South Africa: Calciparine | Heparin;
  • (ZM) Zambia: Heparin sodium fresenius;
  • (ZW) Zimbabwe: Heparin | Heparin sodium fresenius
  1. Ageno W, Gallus AS, Wittkowsky A, Crowther M, Hylek EM, Palareti G. Oral anticoagulant therapy: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141(2 suppl):e44S-e88S. doi: 10.1378/chest.11-2292. [PubMed 22315269]
  2. Ahlfors CE. Benzyl alcohol, kernicterus, and unbound bilirubin. J Pediatr. 2001;139(2):317-319. [PubMed 11487763]
  3. American College of Obstetricians and Gynecologists (ACOG) Committee on Practice Bulletins-Obstetrics. ACOG Practice Bulletin No. 196: Thromboembolism in pregnancy. Obstet Gynecol. 2018;132(1):e1-e17. doi: 10.1097/AOG.0000000000002706. [PubMed 29939938]
  4. American Society of Health-System Pharmacists (ASHP). Pediatric continuous infusion standards. https://www.ashp.org/-/media/assets/pharmacy-practice/s4s/docs/Pediatric-Infusion-Standards.ashx. Updated March 2024. Accessed March 19, 2024.
  5. Amsterdam EA, Wenger NK, Brindis RG, et al; ACC/AHA Task Force Members. 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines [published correction appears in Circulation. 2014;130(25):e433-e444]. Circulation. 2014;130(25):e344-e426. doi: 10.1161/CIR.0000000000000134. [PubMed 25249585]
  6. Andrew M, Marzinotto V, Massicotte P, et al, “Heparin Therapy in Pediatric Patients: A Prospective Cohort Study,” Pediatr Research, 1994, 35(1):78-83. [PubMed 8134203]
  7. Antman EM, Morrow DA, McCabe CH, et al; ExTRACT-TIMI 25 Investigators. Enoxaparin versus unfractionated heparin with fibrinolysis for ST-elevation myocardial infarction. N Engl J Med. 2006;354(14):1477-1488. doi: 10.1056/NEJMoa060898. [PubMed 16537665]
  8. Arepally GM. Heparin-induced thrombocytopenia. Blood. 2017;129(21):2864-2872. doi:10.1182/blood-2016-11-709873 [PubMed 28416511]
  9. Arepally GM, Ortel TL. Heparin-induced thrombocytopenia. Annu Rev Med. 2010;61:77-90. doi:10.1146/annurev.med.042808.171814 [PubMed 20059332]
  10. Arepally GM, Padmanabhan A. Heparin-induced thrombocytopenia: a focus on thrombosis. Arterioscler Thromb Vasc Biol. 2021;41(1):141-152. doi:10.1161/ATVBAHA.120.315445 [PubMed 33267665]
  11. Balestrino D, Quintana M, Charbonnel N, Forestier C, Lartigue C, Souweine B. Compatibility of injectable anticoagulant agents in ethanol; in vitro antibiofilm activity and impact on polyurethane catheters of enoxaparin 400 U/mL in 40% v/v ethanol. PLoS One. 2016;11(7):e0159475. doi: 10.1371/journal.pone.0159475. [PubMed 27441664]
  12. Barbour LA, Kick SD, Steiner JF, et al. A prospective study of heparin-induced osteoporosis in pregnancy using bone densitometry. Am J Obstet Gynecol. 1994;170(3):862-869. doi:10.1016/s0002-9378(94)70299-3 [PubMed 8141217]
  13. Barletta JF, DeYoung JL, McAllen K, Baker R, Pendleton K. Limitations of a standardized weight-based nomogram for heparin dosing in patients with morbid obesity. Surg Obes Relat Dis. 2008;4(6):748-753. doi: 10.1016/j.soard.2008.03.005 [PubMed 18586569]
  14. Based on expert opinion.
  15. Bates SM, Greer IA, Middeldorp S, Veenstra DL, Prabulos AM, Vandvik PO. VTE, thrombophilia, antithrombotic therapy, and pregnancy: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141(2)(suppl):e691S-e736S. doi:10.1378/chest.11-2300 [PubMed 22315276]
  16. Bates SM, Rajasekhar A, Middeldorp S, et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: venous thromboembolism in the context of pregnancy. Blood Adv. 2018;2(22):3317-3359. doi:10.1182/bloodadvances.2018024802 [PubMed 30482767]
  17. Bates SM, Weitz JI, Johnston M, Hirsh J, Ginsberg JS. Use of a fixed activated partial thromboplastin time ratio to establish a therapeutic range for unfractionated heparin. Arch Intern Med. 2001;161(3):385-391. [PubMed 11176764]
  18. Bauer KA. Risk and prevention of venous thromboembolism in adults with cancer. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed October 4, 2021.
  19. Bauer KA. Use of anticoagulants during pregnancy and postpartum. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed September 7, 2023.
  20. Bauer SR, Ou NN, Dreesman BJ, et al. Effect of body mass index on bleeding frequency and activated partial thromboplastin time in weight-based dosing of unfractionated heparin: a retrospective cohort study. Mayo Clin Proc. 2009;84(12):1073-1078. doi: 10.4065/mcp.2009.0220 [PubMed 19955244]
  21. Bjornsson T, Wolfram B, Kitchell B. Heparin kinetics determined by three assay methods. Clin Pharmacol Ther. 1982;31(1):104–113. [PubMed 7053298]
  22. Bookstaver PB, Rokas KE, Norris LB, Edwards JM, Sherertz RJ. Stability and compatibility of antimicrobial lock solutions. Am J Health Syst Pharm. 2013;70(24):2185-2198. doi: 10.2146/ajhp120119. [PubMed 24296841]
  23. Bookstaver PB, Williamson JC, Tucker BK, Raad II, Sherertz RJ. Activity of novel antibiotic lock solutions in a model against isolates of catheter-related bloodstream infections. Ann Pharmacother. 2009;43(2):210-219. doi: 10.1345/aph.1L145. [PubMed 19193593]
  24. Bottio T, Pittarello G, Bonato R, Fagiolo U, Gerosa G. Life-threatening anaphylactic shock caused by porcine heparin intravenous infusion during mitral valve repair. J Thorac Cardiovasc Surg. 2003;126(4):1194-1195. doi:10.1016/s0022-5223(03)00813-4 [PubMed 14566272]
  25. Bradford NK, Edwards RM, Chan RJ. Heparin versus 0.9% sodium chloride intermittent flushing for the prevention of occlusion in long term central venous catheters in infants and children: A systematic review. Int J Nurs Stud. 2016;59:51-59. [PubMed 27222450]
  26. Braun JD. Embolism to the lower extremities. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed January 5, 2022.
  27. Bruen KJ, Ballard JR, Morris SE, Cochran A, Edelman LS, Saffle JR. Reduction of the incidence of amputation in frostbite injury with thrombolytic therapy. Arch Surg. 2007;142(6):546-551. doi:10.1001/archsurg.142.6.546 [PubMed 17576891]
  28. Burch HB. Drug effects on the thyroid. N Engl J Med. 2019;381(8):749-761. doi: 10.1056/NEJMra1901214. [PubMed 31433922]
  29. Burke BJ, Scott GL, Smith PJ, Wakerley GR. Heparin-associated priapism. Postgrad Med J. 1983;59(691):332-333. doi:10.1136/pgmj.59.691.332 [PubMed 6878109]
  30. Butt W, Shann F, McDonnell G, Hudson I. Effect of heparin concentration and infusion rate on the patency of arterial catheters. Crit Care Med. 1987;15(3):230-232. [PubMed 3545674]
  31. Casele H, Haney EI, James A, Rosene-Montella K, Carson M. Bone density changes in women who receive thromboprophylaxis in pregnancy. Am J Obstet Gynecol. 2006;195(4):1109-1113. doi:10.1016/j.ajog.2006.06.080 [PubMed 17000242]
  32. Centers for Disease Control (CDC). Neonatal deaths associated with use of benzyl alcohol—United States. MMWR Morb Mortal Wkly Rep. 1982;31(22):290-291. http://www.cdc.gov/mmwr/preview/mmwrhtml/00001109.htm [PubMed 6810084]
  33. Cloherty JP, Eichenwald EC, Martin CR, eds. Manual of Neonatal Care. 8th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2017.
  34. Cohen M, Demers C, Gurfinkel EP, et al. A comparison of low-molecular-weight heparin with unfractionated heparin for unstable coronary artery disease. Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events Study Group. N Engl J Med. 1997;337(7):447-452. doi: 10.1056/NEJM199708143370702. [PubMed 9250846]
  35. Conway MA, McCollom C, Bannon C. Central venous catheter flushing recommendations: a systematic evidence-based practice review. J Pediatr Oncol Nurs. 2014;31(4):185-190. [PubMed 24794887]
  36. Conway SE, Hwang AY, Ponte CD, Gums JG. Laboratory and clinical monitoring of direct acting oral anticoagulants: what clinicians need to know. Pharmacotherapy. 2017;37(2):236-248. doi:10.1002/phar.1884 [PubMed 27983747]
  37. Corkin MR, ed. Pediatric Nutrition Support Core Curriculum. 2nd edition. Silver Spring, MD: American Society for Parenteral and Enteral Nutrition; 2015.
  38. Cruickshank MK, Levine MN, Hirsh J, et al, “A Standard Heparin Nomogram for the Management of Heparin Therapy,” Arch Intern Med, 1991, 151(2):333-7. [PubMed 1789820]
  39. Cuker A, Arepally GM, Chong BH, et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: heparin-induced thrombocytopenia. Blood Adv. 2018;2(22):3360-3392. doi:10.1182/bloodadvances.2018024489 [PubMed 30482768]
  40. Cutlip D, Levin T. Antithrombotic therapy for elective percutaneous coronary intervention: general use. Connor RF, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed February 6, 2020b.
  41. Cutlip D, Lincoff AM. Anticoagulant therapy in non-ST elevation acute coronary syndromes. Connor RF, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed May 9, 2024.
  42. Dager WE, Dougherty JA, Nguyen PH, et al. Heparin-Induced Thrombocytopenia: Treatment Options and Special Considerations. Pharmacotherapy. 2007;27(4):564-587. [PubMed 17381384]
  43. Dager WE, Gulseth MP, Nutescu EA, eds. Anticoagulation Therapy: A Clinical Practice Guide. 2nd ed. American Society of Health-System Pharmacists; 2018.
  44. Dager WE, Kiser TH. Systemic anticoagulation considerations in chronic kidney disease. Adv Chronic Kidney Dis. 2010;17(5):420-427. doi:10.1053/j.ackd.2010.06.002 [PubMed 20727512]
  45. Dager WE, Tsu LV, Pon TK. Considerations for Systemic Anticoagulation in ESRD. Semin Dial. 2015;28(4):354-362. doi:10.1111/sdi.12376 [PubMed 25951901]
  46. Dahlman TC, Sjöberg HE, Ringertz H. Bone mineral density during long-term prophylaxis with heparin in pregnancy. Am J Obstet Gynecol. 1994;170(5 Pt 1):1315-1320. doi:10.1016/s0002-9378(94)70149-0 [PubMed 8178860]
  47. Davenport A. Anticoagulation for continuous renal replacement therapy. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. August 7, 2020.
  48. Davies MJ, D'Alessio DA, Fradkin J, et al. Management of hyperglycemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2018;41(12):2669-2701. doi:10.2337/dci18-0033 [PubMed 30291106]
  49. Dawes J, Papper DS. Catabolism of low-dose heparin in man. Thromb Res. 1979;14(6):845-860. [PubMed 473122]
  50. Decousus HA, Croze M, Levi FA, et al, “Circadian Changes in Anticoagulant Effect of Heparin Infused at a Constant Rate,” Br Med J (Clin Res Ed), 1985, 290(6465):341-4. [PubMed 3917812]
  51. Deusenberry CM, Bardsley C, Sharon M, Hobbs GR, Wilson AM, Bardes JM. Low molecular weight heparin is superior for venous thromboembolism prophylaxis in high-risk geriatric patients. Am Surg. 2023;89(12):5837-5841. doi:10.1177/00031348231177922 [PubMed 37208855]
  52. de Swart C, Nijmeyer B, Roelofs J, Sixma JJ. Kinetics of intravenously administered heparin in normal humans. Blood. 1982;60(6):1251–1258. [PubMed 7139119]
  53. Douketis JD, Ginsberg JS, Burrows RF, Duku EK, Webber CE, Brill-Edwards P. The effects of long-term heparin therapy during pregnancy on bone density. A prospective matched cohort study. Thromb Haemost. 1996;75(2):254-257. [PubMed 8815571]
  54. Douketis JD, Mithoowani S. Prevention of venous thromboembolic disease in acutely ill hospitalized medical adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed September 27, 2019a.
  55. Douketis JD, Mithoowani S. Prevention of venous thromboembolic disease in adult nonorthopedic surgical patients. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed September 27, 2019b.
  56. Douketis JD, Mithoowani S. Prevention of venous thromboembolism in adults undergoing hip fracture repair or hip or knee replacement. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed December 21, 2022.
  57. Douketis JD, Spyropoulos AC, Spencer FA, et al. Perioperative management of antithrombotic therapy: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines [published correction appears in Chest. 2012;141(4):1129]. Chest. 2012;141(2 suppl):e326S-e350S. doi: 10.1378/chest.11-2298. [PubMed 22315266]
  58. Estes JW. Clinical pharmacokinetics of heparin. Clin Pharmacokinet. 1980;5(3):204-220. doi:10.2165/00003088-198005030-00002 [PubMed 6993082]
  59. Expert opinion. Senior Obesity Editorial Team: Jeffrey F. Barletta, PharmD, FCCM; Manjunath P. Pai, PharmD, FCP; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC.
  60. Expert opinion. Senior Renal Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
  61. Falck-Ytter Y, Francis CW, Johanson NA, et al. Prevention of VTE in orthopedic surgery patients: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141(2 suppl):e278S-e325S. doi: 10.1378/chest.11-2404. [PubMed 22315265]
  62. Faust AC, Kanyer D, Wittkowsky AK. Managing transitions from oral factor Xa inhibitors to unfractionated heparin infusions. Am J Health Syst Pharm. 2016;73(24):2037-2041. doi:10.2146/ajhp150596 [PubMed 27919873]
  63. Ferguson JJ, Califf RM, Antman EM, et al; SYNERGY Trial Investigators. Enoxaparin vs unfractionated heparin in high-risk patients with non-ST-segment elevation acute coronary syndromes managed with an intended early invasive strategy: primary results of the SYNERGY randomized trial. JAMA. 2004;292(1):45-54. doi: 10.1001/jama.292.1.45. [PubMed 15238590]
  64. Flaker GC, Bartolozzi J, Davis V, et al, “Use of a Standardized Heparin Nomogram to Achieve Therapeutic Anticoagulation after Thrombolytic Therapy in Myocardial Infarction. TIMI 4 investigators. Thrombolysis in Myocardial Infarction,” Arch Intern Med, 1994, 154(13):1492-6. [PubMed 8018004]
  65. Freed MD, Keane JF, and Rosenthal A, “The Use of Heparinization to Prevent Arterial Thrombosis After Percutaneous Cardiac Catheterization in Children,” Circulation, 1974, 50(3):565-9. [PubMed 4607271]
  66. Frontera JA, Lewin JJ 3rd, Rabinstein AA, et al; Guideline for reversal of antithrombotics in intracranial hemorrhage: a statement for healthcare professionals from the Neurocritical Care Society and Society of Critical Care Medicine. Neurocrit Care. 2016;24(1):6-46. [PubMed 26714677]
  67. Gajic-Veljanoski O, Phua CW, Shah PS, Cheung AM. Effects of long-term low-molecular-weight heparin on fractures and bone density in non-pregnant adults: a systematic review with meta-analysis. J Gen Intern Med. 2016;31(8):947-957. doi:10.1007/s11606-016-3603-8 [PubMed 26895998]
  68. Garcia DA, Baglin TP, Weitz JI, Samama MM. Parenteral anticoagulants: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines [published corrections appear in Chest. 2012;141(5):1369; Chest. 2013;144(2):721]. Chest. 2012;141(2 suppl):e24S-e43S. doi: 10.1378/chest.11-2291. [PubMed 22315264]
  69. Gerhard-Herman MD, Gornik HL, Barrett C, et al. 2016 AHA/ACC guideline on the management of patients with lower extremity peripheral artery disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines [published correction appears in Circulation. 2017;135(12):e791-e792]. Circulation. 2017;135(12):e726-e779. doi: 10.1161/CIR.0000000000000471. [PubMed 27840333]
  70. Gerlach AT, Folino J, Morris BN, Murphy CV, Stawicki SP, Cook CH. Comparison of heparin dosing based on actual body weight in non-obese, obese and morbidly obese critically ill patients. Int J Crit Illn Inj Sci. 2013;3(3):195-199. doi:10.4103/2229-5151.119200 [PubMed 24404457]
  71. Giglia TM, Massicotte MP, Tweddell JS, et al. Prevention and treatment of thrombosis in pediatric and congenital heart disease: a scientific statement from the American Heart Association. Circulation. 2013;128(24):2622-2703. [PubMed 24226806]
  72. Gonzaga T, Jenabzadeh K, Anderson CP, Mohr WJ, Endorf FW, Ahrenholz DH. Use of intra-arterial thrombolytic therapy for acute treatment of frostbite in 62 patients with review of thrombolytic therapy in frostbite. J Burn Care Res. 2016;37(4):e323-e334. doi:10.1097/BCR.0000000000000245 [PubMed 25950290]
  73. Gould MK, Garcia DA, Wren SM, et al. Prevention of VTE in nonorthopedic surgical patients: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines [published correction appears in Chest. 2012;141(5):1369]. Chest. 2012;141(2 suppl):e227S-e277S. doi: 10.1378/chest.11-2297. [PubMed 22315263]
  74. Guyatt GH, Akl EA, Crowther M, Gutterman DD, Schuünemann HJ; American College of Chest Physicians Antithrombotic Therapy and Prevention of Thrombosis Panel. Executive summary: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines [published corrections appear in Chest. 2012;141(4):1129; Chest. 2012;142(6):1698]. Chest. 2012;141(2 suppl):7S-47S. doi: 10.1378/chest.1412S3 [PubMed 22315257]
  75. Hansen LB, Vondracek SF. Prevention and treatment of nonpostmenopausal osteoporosis. Am J Health Syst Pharm. 2004;61(24):2637-2654. [PubMed 15646699]
  76. Heparin sodium in 0.45% sodium chloride [prescribing information]. Lake Forest, IL: Hospira Inc; March 2022.
  77. Heparin sodium in 0.9% sodium chloride 2 units/mL [prescribing information]. Bethlehem, PA: B. Braun Medical Inc; December 2023.
  78. Heparin sodium in dextrose injection [prescribing information]. Lake Forest, IL: Hospira Inc; March 2022.
  79. Heparin sodium in sodium chloride 2 units/mL [prescribing information]. Lake Forest, IL: Hospira Inc; March 2022.
  80. Heparin sodium injection (single- and multi-dose vials) [prescribing information]. Lake Zurich, IL: Fesenius Kabi; June 2021.
  81. Heparin sodium injection (single- and multi-dose vials) [prescribing information]. Schaumburg, IL: Sagent Pharmaceuticals; May 2022.
  82. Heparin sodium injection [prescribing information]. Rockford, IL: Mylan; June 2022.
  83. Heparin Sodium (Porcine) Lock Flush [prescribing information]. Glendale Heights, IL: Medefil Inc; December 2016.
  84. Hepponstall M, Chan A, Monagle P. Anticoagulation therapy in neonates, children and adolescents. Blood Cells Mol Dis. 2017;67:41-47. [PubMed 28552474]
  85. Hickey S, Whitson A, Jones L, et al. Guidelines for thrombolytic therapy for frostbite. J Burn Care Res. 2020;41(1):176-183. doi:10.1093/jbcr/irz148 [PubMed 31899512]
  86. Hirsh J, Anand SS, Halperin JL, Fuster V; American Heart Association. Guide to anticoagulant therapy: Heparin: a statement for healthcare professionals from the American Heart Association. Circulation. 2001 Jun;103(24):2994-3018. doi:10.1161/01.cir.103.24.2994 [PubMed 11413093]
  87. Hirsh J, Fuster V. Guide to anticoagulant therapy. Part 1: heparin. American Heart Association. Circulation. 1994;89(3):1449-1468. [PubMed 8124829]
  88. Hirsh J, Raschke R, Warkentin TE, Dalen JE, Deykin D, Poller L. Heparin: mechanism of action, pharmacokinetics, dosing considerations, monitoring, efficacy, and safety. Chest. 1995;108(4)(suppl):258S-275S. doi:10.1378/chest.108.4_supplement.258s [PubMed 7555181]
  89. Holbrook A, Schulman S, Witt, DM, et al. Evidence-based management of anticoagulant therapy: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141(2 suppl):e152S-e184S. doi: 10.1378/chest.11-2295. [PubMed 22315259]
  90. Hosch LM, Breedlove EY, Scono LE, Knoderer CA. Evaluation of an unfractionated heparin pharmacy dosing protocol for the treatment of venous thromboembolism in nonobese, obese, and severely obese patients. Ann Pharmacother. 2017;51(9):768-773. doi:10.1177/1060028017709819 [PubMed 28511582]
  91. Hull RD, Garcia DA. Heparin and LMW heparin: dosing and adverse effects. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed January 21, 2022a.
  92. Hull RD, Lip GYH. Venous thromboembolism: Anticoagulation after initial management. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed January 12, 2022b.
  93. Hull RD, Raskob GE, Rosenbloom D, et al, “Optimal Therapeutic Level of Heparin Therapy in Patients with Venous Thromboembolism,” Arch Intern Med, 1992, 152(8):1589-95. [PubMed 1497392]
  94. Ibrahim AE, Goverman J, Sarhane KA, Donofrio J, Walker TG, Fagan SP. The emerging role of tissue plasminogen activator in the management of severe frostbite. J Burn Care Res. 2015;36(2):e62-e66. doi:10.1097/BCR.0000000000000135 [PubMed 25687362]
  95. "Inactive" ingredients in pharmaceutical products: update (subject review). American Academy of Pediatrics (AAP) Committee on Drugs. Pediatrics. 1997;99(2):268-278. [PubMed 9024461]
  96. Jaff MR, McMurtry MS, Archer SL, et al, “Management of Massive and Submassive Pulmonary Embolism, Iliofemoral Deep Vein Thrombosis, and Chronic Thromboembolic Pulmonary Hypertension: A Scientific Statement from the American Heart Association,” Circulation, 2011, 123(16):1788-830. [PubMed 21422387]
  97. Johnson AR, Jensen HL, Peltier G, DelaCruz E. Efficacy of intravenous tissue plasminogen activator in frostbite patients and presentation of a treatment protocol for frostbite patients. Foot Ankle Spec. 2011;4(6):344-348. doi:10.1177/1938640011422596 [PubMed 21965579]
  98. Kahn SR, Lim W, Dunn AS, et al. Prevention of VTE in nonsurgical patients: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141(2 suppl):e195S-e226S. doi: 10.1378/chest.11-2296. [PubMed 22315261]
  99. Kandrotas RJ. Heparin pharmacokinetics and pharmacodynamics. Clin Pharmacokinet. 1992;22(5):359-374. [PubMed 1505142]
  100. Kapetanakis S, Nastoulis E, Demesticha T, Demetriou T. The effect of low molecular weight heparins on fracture healing. Open Orthop J. 2015;9:226-236. doi:10.2174/1874325001509010226 [PubMed 26161162]
  101. Karlaftis V, Sritharan G, Attard C, Corral J, Monagle P, Ignjatovic V. Beta (β)-antithrombin activity in children and adults: implications for heparin therapy in infants and children. J Thromb Haemost. 2014;12(7):1141-1144. doi:10.1111/jth.12597 [PubMed 24801362]
  102. Kearon C, Akl EA, Comerota AJ, et al. Antithrombotic therapy for VTE disease: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines [published correction appears in Chest. 2012;142(6):1698-1704]. Chest. 2012;141(2)(suppl):e419S-e496S. doi: 10.1378/chest.11-2301. [PubMed 22315268]
  103. Kearon C, Akl EA, Ornelas J, et al. Antithrombotic Therapy for VTE disease: CHEST guideline and expert panel report. Chest. 2016;149(2):315-352. doi: 10.1016/j.chest.2015.11.026. [PubMed 26867832]
  104. Key NS, Khorana AA, Kuderer NM, et al. Venous thromboembolism prophylaxis and treatment in patients with cancer: ASCO clinical practice guideline update. J Clin Oncol. 2020;38(5):496-520. doi:10.1200/JCO.19.01461 [PubMed 31381464]
  105. Kincaid EH, Hammon JW. Cardiopulmonary Bypass. In: Yuh DD, Vricella LA, Yang SC, Doty JR. eds. Johns Hopkins Textbook of Cardiothoracic Surgery, Second Edition. New York, NY: McGraw-Hill; 2014.
  106. Konkle BA, Nkomo VT. Antithrombotic therapy for mechanical heart valves. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed May 24, 2022.
  107. Kovalik EC, Davenport A. Anticoagulation for the hemodialysis procedure. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed August 26, 2020.
  108. Krishnaswamy A, Lincoff AM, Cannon CP. Bleeding complications of unfractionated heparin. Expert Opin Drug Saf. 2011;10(1):77-84.doi: 10.1517/14740338.2011.521150 [PubMed 20868290]
  109. Kroon C, de Boer A, Kroon JM, Schoemaker HC, van den Meer FJ, Cohen AF. Influence of skinfold thickness on heparin absorption. Lancet. 1991;337(8747):945-946. doi:10.1016/0140-6736(91)91573-d [PubMed 1678033]
  110. Kulik A, Rubens FD, Wells PS, et al. Early postoperative anticoagulation after mechanical valve replacement: a systematic review. Ann Thorac Surg. 2006;81(2):770-781. doi: 10.1016/j.athoracsur.2005.07.023. [PubMed 16427905]
  111. Lawton JS, Tamis-Holland JE, Bangalore S, et al. 2021 ACC/AHA/SCAI guideline for coronary artery revascularization: a report of the American College of Cardiology/American Heart Association joint committee on clinical practice guidelines. J Am Coll Cardiol. 2022;79(2):e21-e129. doi:10.1016/j.jacc.2021.09.006 [PubMed 34895950]
  112. Lee OK, Johnston L. A systematic review for effective management of central venous catheters and catheter sites in acute care paediatric patients. Worldviews Evid Based Nurs. 2005;2(1):4-13. [PubMed 17040550]
  113. Levito MN, Coons JC, Verrico MM, et al. A systemwide approach for navigating the dilemma of oral factor Xa inhibitor interference with unfractionated heparin anti-factor Xa concentrations. Ann Pharmacother. Published online September 4, 2020. doi:10.1177/1060028020956271 [PubMed 32885997]
  114. Lincoff AM, Cutlip D. Acute ST-elevation myocardial infarction: Management of anticoagulation. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed August 26, 2020.
  115. Linkins LA, Dans AL, Moores LK, Bona R, Davidson BL, Schulman S, Crowther M. Treatment and prevention of heparin-induced thrombocytopenia: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2)(suppl):e495S-e530S. doi:10.1378/chest.11-2303 [PubMed 22315270]
  116. Lip GYH, Hull RD. Venous thromboembolism: Initiation of anticoagulation. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed January 24, 2022.
  117. Lo GK, Juhl D, Warkentin TE, Sigouin CS, Eichler P, Greinacher A. Evaluation of pretest clinical score (4 T's) for the diagnosis of heparin-induced thrombocytopenia in two clinical settings. J Thromb Haemost. 2006;4(4):759-65. doi:10.1111/j.1538-7836.2006.01787.x. [PubMed 16634744]
  118. Malhotra A. Venous thromboembolism in pregnancy and postpartum: treatment. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed October 5, 2023.
  119. Mathews EZ. A fatal case of heparin-induced thrombocytopenia and thrombosis. J Hosp Med. 2010;5(3):E14-5. doi:10.1002/jhm.512 [PubMed 20235296]
  120. McDonald MM, Jacobson LJ, Hay WW Jr, Hathaway WE. Heparin clearance in the newborn. Pediatr Res. 1981;15(7):1015-1018. [PubMed 7254945]
  121. McIntosh SE, Freer L, Grissom CK, et al. Wilderness Medical Society clinical practice guidelines for the prevention and treatment of frostbite: 2019 update. Wilderness Environ Med. 2019;30(4S):S19-S32. doi:10.1016/j.wem.2019.05.002 [PubMed 31326282]
  122. Melloni C, Alexander KP, Chen AY, et al. Unfractionated heparin dosing and risk of major bleeding in non-ST-segment elevation acute coronary syndromes. Am Heart J. 2008;156(2):209-215. doi:10.1016/j.ahj.2008.03.023 [PubMed 18657648]
  123. Mermel LA, Allon M, Bouza E, et al. Clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection: 2009 update by the Infectious Diseases Society of America [published corrections appear in Clin Infect Dis. 2010;50(7):1079; Clin Infect Dis. 2010;50(3):457]. Clin Infect Dis. 2009;49(1):1-45. doi: 10.1086/599376. [PubMed 19489710]
  124. Monagle P, Chan A, Goldenberg NA, et al, "Antithrombotic Therapy in Neonates and Children: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (9th Edition)," Chest, 2012, 141(2 Suppl):e737-801. [PubMed 22315277]
  125. Moreno-Duarte I, Ghadimi K. Heparin induced thrombocytopenia for the perioperative and critical care clinician. Curr Anesthesiol Rep. 2020;10(4):501-511. doi:10.1007/s40140-020-00405-6 [PubMed 32904403]
  126. Morimoto Y, Niwa H, Minematsu K. Risk factors affecting hemorrhage after tooth extraction in patients undergoing continuous infusion with unfractionated heparin. J Oral Maxillofac Surg. 2012;70(3):521-526. [PubMed 22177816]
  127. Narouze S, Benzon HT, Provenzano DA, et al. Interventional spine and pain procedures in patients on antiplatelet and anticoagulant medications: guidelines from the American Society of Regional Anesthesia and Pain Medicine, the European Society of Regional Anaesthesia and Pain Therapy, the American Academy of Pain Medicine, the International Neuromodulation Society, the North American Neuromodulation Society, and the World Institute of Pain. Reg Anesth Pain Med. 2015;40(3):182-212. doi:10.1097/AAP.0000000000000223 [PubMed 25899949]
  128. Nemecek BD, Hammond DA, eds. Demystifying Drug Dosing in Renal Dysfunction. American Society of Health-System Pharmacists; 2019.
  129. Newall F, Johnston L, Ignjatovic V, et al, "Unfractionated Heparin Therapy in Infants and Children," Pediatrics, 2009, 123(3):e510-8. [PubMed 19221154]
  130. Nkomo VT, Konkle BA. Anticoagulation for prosthetic heart valves: management of bleeding and invasive procedures. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed March 14, 2023.
  131. Nygaard RM, Lacey AM, Lemere A, et al. Time matters in severe frostbite: assessment of limb/digit salvage on the individual patient level. J Burn Care Res. 2017;38(1):53-59. doi:10.1097/BCR.0000000000000426 [PubMed 27606554]
  132. O'Gara PT, Kushner FG, Ascheim DD, et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013;61(4):e78-e140. doi: 10.1016/j.jacc.2012.11.019. [PubMed 23256914]
  133. Olsson P, Lagergren H, Ek S. The elimination from plasma of intravenous heparin: An experimental study on dogs and humans. Acta Med Scand. 1963;173:619–630. [PubMed 13940090]
  134. O'Mahony D, Cherubini A, Guiteras AR, et al. STOPP/START criteria for potentially inappropriate prescribing in older people: version 3. Eur Geriatr Med. 2023;14(4):625-632. doi:10.1007/s41999-023-00777-y [PubMed 37256475]
  135. Ortel TL, Neumann I, Ageno W, et al. American Society of Hematology 2020 guidelines for management of venous thromboembolism: treatment of deep vein thrombosis and pulmonary embolism. Blood Adv. 2020;4(19):4693-4738. doi:10.1182/bloodadvances.2020001830 [PubMed 33007077]
  136. Osataphan S, Patell R, Chiasakul T, Khorana AA, Zwicker JI. Extended thromboprophylaxis for medically ill patients with cancer: a systemic review and meta-analysis. Blood Adv. 2021;5(8):2055-2062. doi:10.1182/bloodadvances.2020004118 [PubMed 33861298]
  137. Otto CM, Nishimura RA, Bonow RO, et al. 2020 ACC/AHA guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2021;143(5):e72-e227. doi:10.1161/CIR.0000000000000923 [PubMed 33332150]
  138. Paine RE, Turner EN, Kloda D, Falank C, Chung B, Carter DW. Protocoled thrombolytic therapy for frostbite improves phalangeal salvage rates. Burns Trauma. 2020;8:tkaa008. doi:10.1093/burnst/tkaa008 [PubMed 32341921]
  139. Panday K, Gona A, Humphrey MB. Medication-induced osteoporosis: screening and treatment strategies. Ther Adv Musculoskelet Dis. 2014;6(5):185-202. doi:10.1177/1759720X14546350 [PubMed 25342997]
  140. Pasquale LD, Ferneini EM. Heparin and Lovenox: What the Oral and Maxillofacial Surgeon Needs to Know. Oral Maxillofac Surg Clin North Am. 2016;28(4):507-513. [PubMed 27624773]
  141. Patanwala AE, Seaman SM, Kopp BJ, Erstad BL. Heparin dosing for venous thromboembolism prophylaxis in obese hospitalized patients: an observational study. Thromb Res. 2018;169:152-156. doi:10.1016/j.thromres.2018.07.027 [PubMed 30071480]
  142. Raschke RA, Reilly BM, Guidry JR, et al, “The Weight-Based Heparin Dosing Nomogram Compared With a “Standard Care” Nomogram: A Randomized Controlled Trial,” Ann Intern Med, 1993, 119(9):874-81. [PubMed 8214998]
  143. Refer to manufacturer's labeling.
  144. Regitz-Zagrosek V, Roos-Hesselink JW, Bauersachs J, et al; ESC Scientific Document Group. 2018 ESC guidelines for the management of cardiovascular diseases during pregnancy. Eur Heart J. 2018;39(34):3165-3241. doi: 10.1093/eurheartj/ehy340. [PubMed 30165544]
  145. Riney JN, Hollands JM, Smith JR, Deal EN. Identifying optimal initial infusion rates for unfractionated heparin in morbidly obese patients. Ann Pharmacother. 2010;44(7-8):1141-1151. doi:10.1345/aph.1P088 [PubMed 20587743]
  146. Samuel S, Iluonakhamhe EK, Adair E, et al. High dose subcutaneous unfractionated heparin for prevention of venous thromboembolism in overweight neurocritical care patients. J Thromb Thrombolysis. 2015;40(3):302-307. doi:10.1007/s11239-015-1202-x [PubMed 25736986]
  147. Sharma A, Chatterjee S, Lichstein E, Mukherjee D. Extended thromboprophylaxis for medically ill patients with decreased mobility: does it improve outcomes? J Thromb Haemost. 2012;10(10):2053-2060. doi: 10.1111/j.1538-7836.2012.04874.x. [PubMed 22863355]
  148. Shen JI, Winkelmayer WC. Use and safety of unfractionated heparin for anticoagulation during maintenance hemodialysis. Am J Kidney Dis. 2012;60(3):473-486. doi:10.1053/j.ajkd.2012.03.017 [PubMed 22560830]
  149. Shin S, Harthan EF. Safety and efficacy of the use of institutional unfractionated heparin protocols for therapeutic anticoagulation in obese patients: a retrospective chart review. Blood Coagul Fibrinolysis. 2015;26(6):655-660. doi:10.1097/MBC.0000000000000336 [PubMed 26236941]
  150. Shlensky JA, Thurber KM, O'Meara JG, et al. Unfractionated heparin infusion for treatment of venous thromboembolism based on actual body weight without dose capping. Vasc Med. 2020;25(1):47-54. doi:10.1177/1358863X19875813 [PubMed 31623539]
  151. Signorelli SS, Scuto S, Marino E, Giusti M, Xourafa A, Gaudio A. Anticoagulants and osteoporosis. Int J Mol Sci. 2019;20(21):5275. doi:10.3390/ijms20215275 [PubMed 31652944]
  152. Smythe MA, Nutescu EA, and Wittkowsky AK, "Changes in the USP Heparin Monograph and Implications for Clinicians," Pharmacotherapy, 2010, 30(5):428-31. [PubMed 20411994]
  153. Steg PG, Jolly SS, Mehta SR, et al; FUTURA/OASIS-8 Trial Group. Low-dose vs standard-dose unfractionated heparin for percutaneous coronary intervention in acute coronary syndromes treated with fondaparinux: the FUTURA/OASIS-8 randomized trial. JAMA. 2010;304(12):1339-1349. doi: 10.1001/jama.2010.1320. [PubMed 20805623]
  154. Steg PG, van 't Hof A, Hamm CW, et al; EUROMAX Investigators. Bivalirudin started during emergency transport for primary PCI. N Engl J Med. 2013;369(23):2207-2217. doi: 10.1056/NEJMoa1311096. [PubMed 24171490]
  155. Stone GW, McLaurin BT, Cox DA, et al; ACUITY Investigators. Bivalirudin for patients with acute coronary syndromes. N Engl J Med. 2006;355(21):2203-2216. doi: 10.1056/NEJMoa062437. [PubMed 17124018]
  156. Streiff MB, Holmstrom B, Ashrani A, et al. Cancer-associated venous thromboembolic disease, version 1.2015. J Natl Compr Canc Netw. 2015;13(9):1079-1095. doi:10.6004/jnccn.2015.0133 [PubMed 26358792]
  157. Su HM, Voon WC, Chu CS, Lin TH, Lai WT, Sheu SH. Heparin-induced cardiac tamponade and life-threatening hyperkalema in a patient with chronic hemodialysis. Kaohsiung J Med Sci. 2005;21(3):128-233. doi:10.1016/s1607-551x(09)70289-x [PubMed 15875438]
  158. Tapson VF, Weinberg AS. Thrombolytic (fibrinolytic) therapy in acute pulmonary embolism and lower extremity deep vein thrombosis. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed September 27, 2019.
  159. Topjian AA, Raymond TT, Atkins D, et al. Part 4: Pediatric basic and advanced life support: 2020 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2020;142(16 Suppl 2):S469-S523. doi:10.1161/CIR.0000000000000901 [PubMed 33081526]
  160. Tsujimoto H, Tsujimoto Y, Nakata Y, et al. Pharmacological interventions for preventing clotting of extracorporeal circuits during continuous renal replacement therapy. Cochrane Database Syst Rev. Published online March 13, 2020. doi:10.1002/14651858.CD012467.pub2 [PubMed 32164041]
  161. Vandiver JW, Vondracek TG. Antifactor Xa levels versus activated partial thromboplastin time for monitoring unfractionated heparin. Pharmacotherapy. 2012;32(6):546-558. doi: 10.1002/j.1875-9114.2011.01049.x. [PubMed 22531940]
  162. Vermont Oxford Network (VON). Neonatal drug concentrations. Updated November 2022. Accessed March 19, 2024. https://public.vtoxford.org/wp-content/uploads/2022/11/Neonatal-Drug-Concentrations-Updated-November-2022.pdf
  163. Wada H, Thachil J, Di Nisio M, Mathew P, et al; The Scientific Standardization Committee on DIC of the International Society on Thrombosis Haemostasis. Guidance for diagnosis and treatment of DIC from harmonization of the recommendations from three guidelines [published online February 4, 2013]. J Thromb Haemost. doi: 10.1111/jth.12155. [PubMed 23379279]
  164. Wallentin L, Goldstein P, Armstrong PW, et al. Efficacy and safety of tenecteplase in combination with the low-molecular-weight heparin enoxaparin or unfractionated heparin in the prehospital setting: the Assessment of the Safety and Efficacy of a New Thrombolytic Regimen (ASSENT)-3 PLUS randomized trial in acute myocardial infarction. Circulation. 2003;108(2):135-142. doi: 10.1161/01.CIR.0000081659.72985.A8. [PubMed 12847070]
  165. Warkentin TE and Kelton JG, “Temporal Aspects of Heparin-Induced Thrombocytopenia,” N Engl J Med, 2001, 344(17):1286-92. [PubMed 11320387]
  166. Whitlock RP, Sun JC, Fremes SE, Rubens FD, Teoh KH. Antithrombotic and thrombolytic therapy for valvular disease: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141(2 suppl):e576S-e600S. doi: 10.1378/chest.11-2305. [PubMed 22315272]
  167. Yamaji H, Murakami T, Hina K, et al. Differences in activated clotting time and initial heparin dosage during atrial fibrillation ablation for patients with edoxaban compared with warfarin. J Cardiovasc Electrophysiol. 2018;29(6):835-843. doi: 10.1111/jce.13483. [PubMed 29533476]
  168. Yang S, Niu Q, Gan L, Zhang X, Tu L, Zuo L. Effect of long-term use of unfractionated or low-molecular-weight heparin on bone mineral density in maintenance hemodialysis patients. Hemodial Int. 2020;24(3):374-382. doi:10.1111/hdi.12854 [PubMed 32520445]
  169. Yevzlin AS, Sanchez RJ, Hiatt JG, et al. Concentrated heparin lock is associated with major bleeding complications after tunneled hemodialysis catheter placement. Semin Dial. 2007;20(4):351-354. doi: 10.1111/j.1525-139X.2007.00294.x. [PubMed 17635828]
  170. You JJ, Singer DE, Howard PA, et al; American College of Chest Physicians. Antithrombotic therapy for atrial fibrillation: Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141(2 suppl):e531S-e575S. doi: 10.1378/chest.11-2304. [PubMed 22315271]
  171. Zafren K, Mechem CC. Frostbite: Emergency care and prevention. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed July 1, 2022.
  172. Zidane M, Schram MT, Planken EW, Molendijk WH, Rosendaal FR, van der Meer FJ, Huisman MV. Frequency of major hemorrhage in patients treated with unfractionated intravenous heparin for deep venous thrombosis or pulmonary embolism: a study in routine clinical practice. Arch Intern Med. 2000;160(15):2369-2373. doi:10.1001/archinte.160.15.2369 [PubMed 10927736]
Topic 8518 Version 716.0

آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟