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Management of antithrombotic therapy for a prosthetic heart valve during pregnancy

Management of antithrombotic therapy for a prosthetic heart valve during pregnancy
Literature review current through: May 2024.
This topic last updated: Feb 20, 2024.

INTRODUCTION — Pregnancy presents a unique set of problems for females with prosthetic heart valves. Patients with mechanical prosthetic valves require therapeutic long-term anticoagulation. In contrast, patients with bioprosthetic valves generally do not require long-term anticoagulation but face a higher long-term risk of developing valve dysfunction.

Antithrombotic therapy for prosthetic heart valves during pregnancy is discussed here.

Other prosthetic valve and native valve issues during pregnancy are discussed separately. (See "Management of risks of prosthetic valves during pregnancy" and "Pregnancy and valve disease".)

The use of anticoagulants during pregnancy for indications other than a prosthetic valve is discussed separately. (See "Use of anticoagulants during pregnancy and postpartum".)

PRECONCEPTION EVALUATION AND COUNSELING — Females of childbearing age who have prosthetic heart valves should receive preconception evaluation and counseling regarding risks associated with prosthetic valves and the risks and benefits of antithrombotic therapy, as discussed separately. (See "Management of risks of prosthetic valves during pregnancy", section on 'Preconception evaluation and counseling'.)

Counseling of females of childbearing age with native valve disease with an indication for valve replacement should include discussion comparing the benefits and risks associated with bioprosthetic and mechanical valves (including lifelong need for anticoagulation and greater prosthetic valve longevity with the latter), as discussed separately. (See "Management of risks of prosthetic valves during pregnancy", section on 'Preconception evaluation and counseling' and "Pregnancy and valve disease", section on 'Interventions prior to pregnancy'.)

BIOPROSTHETIC VALVE MANAGEMENT DURING PREGNANCY

General approach — For patients with a surgical or transcatheter bioprosthetic valve, we suggest continuing daily low-dose aspirin (75 to 100 mg/day; eg, 81 mg/day) during pregnancy. (See 'Aspirin' below and "Antithrombotic therapy for mechanical heart valves", section on 'Selective use of aspirin'.)

Patients with bioprosthetic valves do not generally require anticoagulation unless there is a concurrent indication for anticoagulation (eg, atrial fibrillation or prior history of bioprosthetic valve thrombosis). When anticoagulation is required in this setting, low-dose aspirin is generally continued.

Peripartum and postpartum management is discussed below. (See 'Approach for planned delivery' below and 'Postpartum management' below.)

For a recently implanted valve — The following considerations apply to the uncommon setting of a patient who is pregnant during the first three to six months after valve implantation:

Surgical valves – For a patient who is pregnant during the first three to six months after surgical bioprosthetic valve implantation, we do not routinely anticoagulate, since the evidence for intermediate-term anticoagulation in nonpregnant patients with surgical bioprosthetic valves is limited. (See "Antithrombotic therapy for surgical bioprosthetic valves and surgical valve repair", section on 'Approach for surgical bioprosthetic valves' and "Antithrombotic therapy for surgical bioprosthetic valves and surgical valve repair", section on 'Intermediate- and long-term antithrombotic therapy'.)

Transcatheter valves – For a patient who is pregnant during the first three to six months after transcatheter heart valve implantation, we treat with a single antiplatelet agent (aspirin 75 to 100 mg/day). Patients with transcatheter heart valves are generally treated with single antiplatelet therapy (low-dose aspirin or clopidogrel) for life. Although some clinicians treat nonpregnant patients with dual antiplatelet therapy (low-dose aspirin plus clopidogrel) during the first three to six months (three months for an Evolut R/PRO/PRO-PLUS valve; six months for a SAPIEN valve) after valve implantation followed by single antiplatelet therapy, evidence now supports proceeding directly to single antiplatelet therapy. (See "Transcatheter aortic valve implantation: Antithrombotic therapy", section on 'Without concurrent indication for therapeutic anticoagulation'.)

Prior bioprosthetic valve thrombosis — Management of anticoagulation during pregnancy for patients who require anticoagulation due to prior history of bioprosthetic valve thrombosis is the same as for mechanical valves as described below. (See "Bioprosthetic valve thrombosis, thromboembolism, and obstruction: Management" and 'Mechanical valve management during pregnancy' below.)

MECHANICAL VALVE MANAGEMENT DURING PREGNANCY — The absence of relevant randomized trials and the paucity of prospective cohort data make it difficult to offer definitive recommendations on an antithrombotic regimen for prosthetic valves during pregnancy [1,2]. Our approach is presented here.

General considerations — Patients with mechanical prosthetic valves require long-term antithrombotic therapy comprised of anticoagulation plus low-dose aspirin. (See "Antithrombotic therapy for mechanical heart valves".)

Anticoagulation – Therapeutic anticoagulation with frequent monitoring is essential for all pregnant patients with mechanical prosthetic heart valves to prevent valve thrombosis and thromboembolic events [1,2]. Care should be provided by a specialized center capable of intensive management of anticoagulation during pregnancy and delivery. Given the absence of adequate prospective controlled trials and the differing maternal and fetal risks associated with various anticoagulants, the optimum anticoagulant regimen is uncertain [1-4]. (See "Bioprosthetic valve thrombosis, thromboembolism, and obstruction: Clinical manifestations and diagnosis".)

The anticoagulant in this setting is generally vitamin K antagonist (VKA; eg, warfarin) or subcutaneous (SC) low molecular weight heparin (LMWH). If LMWH and/or adequate access to anti-Xa activity monitoring are unavailable due to resource limitations, inpatient dose-adjusted continuous intravenous (IV) infusion of unfractionated heparin (UFH) is a potential option as a last resort, but the safety and efficacy of this treatment over weeks are uncertain, given difficulties in monitoring IV UFH, the limited efficacy of UFH in this setting, and the risk of infection.

The choice of anticoagulant regimen during pregnancy is based upon careful consideration of maternal and fetal risks associated with various types of anticoagulants (table 1). The risk of developing thromboembolic complications during pregnancy should be balanced against the risk of maternal and fetal complications of anticoagulation during pregnancy and delivery. A woman's individual risk of thromboembolic complications is estimated based upon the type of anticoagulant used during pregnancy, the number, type, size, and site of the mechanical valve, and other factors, such as previous thromboembolic complications. Pregnant patients with mechanical valves should be fully informed about the importance of therapeutic anticoagulation throughout pregnancy and the maternal and fetal risks associated with each anticoagulant regimen. The patient's values and preferences inform decision making in this setting. The patient should participate in and agree with decisions about the treatment regimen. (See "Management of risks of prosthetic valves during pregnancy", section on 'Prosthetic valve thrombosis' and "Bioprosthetic valve thrombosis, thromboembolism, and obstruction: Management".)

Our approach to anticoagulation in this setting is in broad agreement with recommendations in the 2020 American College of Cardiology/American Heart Association (ACC/AHA) valvular heart disease guideline [5]. Some similar recommendations are included in the 2021 European Society of Cardiology (ESC) valve disease guidelines and the 2023 British Society for Haematology guideline for anticoagulant management of mechanical heart valves in pregnancy [6,7].

Aspirin – For patients with mechanical valves, we suggest low-dose aspirin (75 to 100 mg/day; eg, 81 mg/day) during pregnancy in addition to the chosen anticoagulation regimen (VKA or heparin). Of note, there is variation in clinical practice in this setting, with some clinicians administering low-dose aspirin only during periods of heparin anticoagulation (LMWH or UFH). Recommendations for low-dose aspirin use (in addition to anticoagulation) for pregnant patients with prosthetic valves have varied, given limited evidence on its use in this setting. The 2020 ACC/AHA valve guidelines note that low-dose aspirin can be continued in pregnant patients with mechanical valves if needed for other indications [5]. In contrast, the 2018 ESC guidelines for management of cardiovascular diseases during pregnancy do not recommend the addition of low-dose aspirin to anticoagulation (with VKA or heparin) in patients with mechanical valves, citing the potential risk of hemorrhage [2]. (See 'Peripartum management' below and 'Aspirin' below and "Antithrombotic therapy for mechanical heart valves", section on 'Selective use of aspirin'.)

With risk factors for prosthetic valve thrombosis — For pregnant patients with a mechanical valve with one or more of the following risk factors for prosthetic valve thrombosis/thromboembolism, we suggest continuing VKA (eg, warfarin) with close international normalized ratio (INR) monitoring throughout pregnancy until 36 weeks along with continuing low-dose aspirin (algorithm 1). In making this recommendation, we are placing high value on reducing maternal risk. (See 'Vitamin K antagonist' below.)

Risk factors for prosthetic valve thrombosis/thromboembolism (see "Antithrombotic therapy for mechanical heart valves" and "Antithrombotic therapy for mechanical heart valves", section on 'Prosthetic valve thrombosis'):

Mechanical mitral valve

Mechanical tricuspid valve

Persistent or paroxysmal atrial fibrillation or flutter

Previous prosthetic valve thromboembolic complication

Multiple mechanical heart valves

However, pregnant patients who place a high value on reducing fetal risk may reasonably choose dose-adjusted twice-daily SC LMWH plus low-dose aspirin (75 to 100 mg/day; eg, 81 mg/day) during the first trimester. (See 'Low molecular weight heparin' below and 'Vitamin K antagonist' below.)

Without risk factors for prosthetic valve thrombosis — For patients with a mechanical valve without any risk factor for prosthetic valve thrombosis, the anticoagulant selected for the first trimester may or may not differ from that chosen for the later trimesters.

During the first trimester — For pregnant patients with a mechanical valve without one or more of the above risk factors for prosthetic valve thrombosis/thromboembolism, low-dose aspirin (75 to 100 mg/day; eg, 81 mg/day) is continued and an anticoagulant is selected according to the following approach (algorithm 1):

The approach during the first trimester is based upon the baseline warfarin dose:

For patients with relatively low baseline VKA dose (warfarin dose ≤5 mg/day, phenprocoumon ≤3 mg/day, or acenocoumarol ≤2 mg/day), the main options for anticoagulation are:

Continuing VKA with close INR monitoring throughout the first trimester. (See 'Vitamin K antagonist' below.)

OR

Dose-adjusted SC LMWH from 5 to 12 weeks is an alternative for patients who wish to avoid the fetal risks associated with low-dose warfarin during the first trimester; twice daily dosing with close monitoring is necessary to prevent thromboembolic complications. (See 'Low molecular weight heparin' below.)

However, if LMWH with appropriate monitoring is unavailable due to resource limitations and the patient refuses VKA therapy, dose-adjusted continuous inpatient IV infusion of UFH (with targeted activated partial thromboplastin time [aPTT] 2 to 2.5 times control) is a potential option, although the efficacy and safety of this treatment over weeks are uncertain, given difficulties in monitoring IV UFH, the limited efficacy of UFH in this setting, and the risk of infection. (See 'Unfractionated heparin' below.)

For patients whose baseline VKA dose is high (defined as warfarin >5 mg/day, phenprocoumon >3 mg/day, or acenocoumarol >2 mg/day), we suggest switching to dose-adjusted SC LMWH throughout the first trimester. Once pregnancy is confirmed, and ideally before the fifth week of gestation, LMWH should be dosed at least twice daily (target anti-Xa activity 1.0 to 1.2 units/mL for mitral valve prosthesis and 0.8 to 1.0 units/mL for aortic valve prosthesis at three to four hours postdose). We recommend checking trough activity as well (proposed minimum trough level of 0.6 units/mL [8]), although the efficacy and safety of this approach have not been established. A plan should be made prior to conception as to how this change in therapy will be arranged. (See 'Low molecular weight heparin' below.)

If LMWH and/or adequate access to anti-Xa activity monitoring are unavailable due to resource limitations, dose-adjusted continuous IV infusion of UFH (with an aPTT 2 to 2.5 times control) is a potential option, although the efficacy and safety of this treatment over weeks are uncertain. (See 'Unfractionated heparin' below.)

For patients with a high baseline VKA dose, some clinicians offer the option of continued VKA during the first trimester after fully informed consent. (See 'General considerations' above and 'Vitamin K antagonist' below.)

During the second and third trimester — During the second trimester and third trimester until 36 weeks or 10 days prior to planned induction of labor or cesarean delivery (whichever is earlier):

We suggest VKA (eg, warfarin; adjusted to INR goal) plus aspirin 75 to 100 mg daily until approximately 36 weeks as the safest option for the mother. Timing of the transition of VKA to LMWH at 36 weeks may need to be individualized for females at high risk for preterm delivery (eg, females with multifetal gestation or previous preterm delivery).

If the mother chooses to avoid the fetal risk associated with VKA therapy, we suggest therapeutic SC LMWH plus aspirin 75 to 100 mg daily. Therapeutic SC LMWH is dosed twice daily with dose adjusted to achieve target anti-Xa activity of 1.0 to 1.2 units/mL for mitral valve prosthesis and 0.8 to 1.0 units/mL for aortic valve prosthesis at four to six hours postdose and ensuring adequate trough activity as well.

If LMWH is unavailable in low-resource settings, VKA is the preferred anticoagulant. Dose-adjusted SC UFH (with regular monitoring to ensure the six-hour postdose aPTT is at least twice baseline) plus aspirin 75 to 100 mg daily is offered as an alternative option (last resort) when LMWH is unavailable only if the mother declines to take warfarin. Use of SC UFH in this setting is controversial and not endorsed by some experts who instead suggest dose-adjusted continuous IV UFH (with aPTT at least two times control) given studies showing high risk of valve thrombosis with SC UFH, particularly with older-generation valve prostheses [1]. However, chronic IV UFH is associated with risk of catheter-related infection.

Management of antithrombotic therapy from 36 weeks (or 10 days prior to planned induction of labor or cesarean delivery, whichever is earlier) to delivery is discussed below. (See 'Peripartum management' below.)

PERIPARTUM MANAGEMENT — Whenever possible, delivery should be planned and its modality discussed in close collaboration with the obstetrician/maternal-fetal medicine specialist, cardiologist, thrombosis expert, and anesthesiologist [9].

Planned inductions or cesarean deliveries are necessary to safely transition and manage anticoagulants. Vaginal delivery is preferred in most cases, and cesarean delivery should be reserved for specific obstetrical indications. However, for females who present in labor on vitamin K antagonist (VKA) or those with advanced heart failure and hemodynamic instability despite treatment, urgent cesarean delivery is suggested [10,11]. (See "Pregnancy in women with congenital heart disease: General principles", section on 'Role of cesarean delivery' and "Acquired heart disease and pregnancy", section on 'Mode and timing of delivery' and 'Approach for planned delivery' below and 'Approach for urgent delivery' below.)

Labor and delivery involve additional hemodynamic and hemorrhagic risks (including the risk of spinal epidural hematoma [SEH] with neuraxial anesthesia) in a woman with a prosthetic heart valve. Due to a lack of relevant data and the impact of patient-specific variables, standard guidelines do not exist, and management in each case should be individualized with input from the patient, her obstetrician, cardiologist, thrombosis expert, and an anesthesiologist. For patients who require anticoagulation, a plan for anticoagulation in labor/peripartum should be agreed upon by obstetricians, anesthesiologists, cardiologists, and hematologists and documented clearly. The risks of valve thrombosis and obstetric hemorrhage as well as the risks and benefits of regional analgesia/anesthesia need to be balanced and the patient fully informed of the rationale for the individualized plan. (See "Labor and delivery: Management of the normal first stage" and "Cesarean birth: Postoperative care, complications, and long-term sequelae", section on 'Complications' and "Assisted (operative) vaginal birth: Overview", section on 'Adverse effects and complications' and "Neuraxial analgesia for labor and delivery (including instrumental delivery)" and "Neuraxial anesthesia/analgesia techniques in the patient receiving anticoagulant or antiplatelet medication" and 'Anesthesia concerns' below.)

Vaginal or cesarean delivery is not generally an indication for routine antibiotic prophylaxis for endocarditis; possible exceptions are discussed separately. (See "Pregnancy and valve disease", section on 'Endocarditis prophylaxis'.)

Anesthesia concerns — Antithrombotic therapy may increase the risk of SEH after neuraxial analgesia/anesthesia. Guidelines have been developed for the timing of neuraxial anesthesia techniques before and after administration of anticoagulant and antiplatelet drugs, with the goal of reducing the risk of SEH, a rare but potentially devastating condition. These guidelines are based on expert opinion and the pharmacokinetics of the individual drugs, and are largely consistent with the approach outlined in this topic. (See "Neuraxial anesthesia/analgesia techniques in the patient receiving anticoagulant or antiplatelet medication", section on 'Spinal epidural hematoma (SEH)'.)

Patients receiving antithrombotic therapy during the peripartum period should undergo antenatal anesthesia evaluation, preferably before 28 weeks gestation [12]; a multidisciplinary, individualized plan should be created for management of antithrombotic therapy and analgesia/anesthesia for planned and/or urgent delivery, considering the following:

The small, unknown risk of SEH with neuraxial analgesia/anesthesia.

The risk of thromboembolic complications.

The optimal method for labor analgesia, given the patient's cardiac physiology, predictors for difficult airway management, and values and preferences. (See "Anesthesia for labor and delivery in high-risk heart disease: Specific lesions" and "Neuraxial analgesia for labor and delivery (including instrumental delivery)" and "Pharmacologic management of pain during labor and delivery" and "Airway management for the pregnant patient".)

The risks associated with general anesthesia if cesarean delivery is necessary.

Approach for planned delivery

For patients with a bioprosthetic valve:

On aspirin only – For patients with a bioprosthetic valve receiving aspirin as the sole antithrombotic therapy, cessation of aspirin prior to delivery is not required if no other antithrombotic agents will be administered during the peripartum period. (See 'Aspirin' below and "Neuraxial anesthesia/analgesia techniques in the patient receiving anticoagulant or antiplatelet medication", section on 'Aspirin and other nonsteroidal antiinflammatory drugs' and "Antithrombotic therapy for mechanical heart valves", section on 'Selective use of aspirin'.)

On aspirin plus an anticoagulant For patients with a bioprosthetic valve receiving aspirin plus anticoagulant, if continued anticoagulation is required postpartum, management should be discussed with an anesthesiologist as aspirin with concurrent early postpartum anticoagulation may increase the risk of SEH. United States anesthesia guidelines recommend generally stopping aspirin 7 to 10 days prior to neuraxial analgesia/anesthesia in patients receiving other antithrombotic medications (before or soon after neuraxial catheter placement or removal) given the potential increased risk of SEH [13]. (See 'Aspirin' below and "Neuraxial anesthesia/analgesia techniques in the patient receiving anticoagulant or antiplatelet medication", section on 'Aspirin and other nonsteroidal antiinflammatory drugs' and "Antithrombotic therapy for mechanical heart valves", section on 'Selective use of aspirin'.)

For patients with a mechanical valve (and therefore receiving aspirin plus an anticoagulant), to minimize the risks of maternal and fetal hemorrhage, the following changes in antithrombotic therapy for females with mechanical valves should be made as the time for delivery approaches:

At approximately 36 weeks or at least 10 days before planned induction of labor or cesarean delivery (whichever is earlier), VKA (eg, warfarin) should be switched to dose-adjusted subcutaneous (SC) low molecular weight heparin (LMWH) administered at least twice daily (target anti-Xa activity 1.0 to 1.2 units/mL for mitral valve replacement and 0.8 to 1.0 units/mL for aortic valve replacement at four to six hours postdose with consideration of checking trough activity as well). Dose-adjusted continuous infusion of unfractionated heparin (UFH; maintaining an activated partial thromboplastin time [aPTT] at 2 to 2.5 times control) should only be offered if LMWH is unavailable. Of note, the approach presented here of transitioning from VKA to LMWH differs from the approach included in the 2014 American Heart Association/American College of Cardiology (AHA/ACC) valve guideline, which instead recommends continuous IV UFH [1].

We generally continue low-dose aspirin along with the chosen heparin regimen (LMWH or UFH) up until planned delivery, despite planned early postpartum administration of anticoagulants. This should be discussed with the anesthesiologist, as aspirin with concurrent early postpartum anticoagulation may increase the risk of SEH and the risk of postpartum hemorrhage and wound hematoma. United States anesthesia guidelines recommend generally stopping aspirin 7 to 10 days prior to neuraxial analgesia/anesthesia in patients receiving other antithrombotic medications (before or soon after neuraxial catheter placement or removal) given the potential increased risk of SEH [13]. However, management of antithrombotic therapy in the parturient with a mechanical prosthetic valve requires risk/benefit analysis. (See "Neuraxial anesthesia/analgesia techniques in the patient receiving anticoagulant or antiplatelet medication", section on 'Aspirin and other nonsteroidal antiinflammatory drugs'.)

The last dose of dose-adjusted SC LMWH is administered 24 hours before planned induction of labor or cesarean delivery if the mother has normal kidney function. This is to facilitate use of regional anesthesia/analgesia and minimize the risk of bleeding at delivery. Various options then exist:

-Use of dose-adjusted IV UFH (target aPTT at least twice control). Twelve hours after cessation of LMWH, IV UFH is commenced with no loading dose at 1000 to 1250 units/hour (eg, 18 units/kg/hour) and the infusion rate is adjusted at six hourly intervals to achieve an aPTT that is twice control. IV UFH is stopped prior to delivery. The timing of the cessation of IV UFH can be difficult when the woman is induced. IV UFH should be discontinued four to six hours prior to initiation of neuraxial anesthesia or analgesia. A neuraxial catheter can be placed once the aPTT has returned to normal. (See "Neuraxial anesthesia/analgesia techniques in the patient receiving anticoagulant or antiplatelet medication", section on 'Intravenous UFH'.)

OR

-Use of intermittent prophylactic doses of LMWH (eg, enoxaparin 40 mg subcutaneously once daily). Initiation of neuraxial anesthesia or analgesia should be delayed for at least 12 hours after the last dose of prophylactic LMWH. Cesarean delivery is performed 24 hours after the last treatment dose or 12 hours after the last prophylactic dose of LMWH. (See "Neuraxial anesthesia/analgesia techniques in the patient receiving anticoagulant or antiplatelet medication", section on 'LMWH thromboprophylaxis'.)

OR

-Induction of labor is commenced 24 hours after the last therapeutic dose of LMWH, and an early epidural catheter is sited. At least 12 hours after nontraumatic (at least 24 hours after traumatic) epidural catheter placement, a prophylactic dose of LMWH is given if the woman is not in active labor and repeated every 24 hours until the woman is in active labor (cervix is dilated to 6 cm or more). (See "Neuraxial anesthesia/analgesia techniques in the patient receiving anticoagulant or antiplatelet medication", section on 'Guidelines for timing of neuraxial anesthesia procedures'.)

Approach for urgent delivery — On rare occasions, urgent delivery is indicated when a woman with a mechanical valve (or with a bioprosthetic valve and requiring anticoagulation) is still receiving therapeutic anticoagulation. Management involves balancing the risk of life-threatening maternal hemorrhage against the potentially catastrophic risk of thromboembolism or valve thrombosis if anticoagulation is reversed and the fetal consequences of not performing urgent delivery. (See "Management of risks of prosthetic valves during pregnancy", section on 'Prosthetic valve thrombosis'.)

Because the likelihood of serious hemorrhagic and thromboembolic complications cannot be accurately quantified, there are differing opinions regarding when and how aggressively to reverse anticoagulation. Full reversal of anticoagulation is not necessary for either vaginal or cesarean delivery. However, if the woman is on warfarin, reversal with vitamin K is appropriate to try to protect the fetus from hemorrhage. Full reversal is also warranted in patients with life-threatening maternal hemorrhage.

In a patient on VKA with an elevated international normalized ratio (INR; therapeutic or supratherapeutic) at the time of an urgent delivery, we suggest the following:

Because the fetus is also therapeutically anticoagulated, we favor cesarean delivery to reduce the risk of fetal trauma and intracranial hemorrhage (as suggested in the 2011 European Society of Cardiology guidelines [10]), though evidence is lacking and the risk of maternal hemorrhage is increased with cesarean delivery.

When urgent or emergency delivery is necessary, the following steps should be taken:

Warfarin should be stopped and four-factor prothrombin complex concentrate (PCC) should be administered to a target INR of 2.0. If a four-factor PCC is unavailable, a three-factor PCC can be given. If no PCC product is available, fresh frozen plasma (FFP) can be administered (initial dose, 15 to 30 mL/kg). FFP administration is not generally sufficient in an emergency situation, given the time required for administration, and thus is not recommended. (See "Management of warfarin-associated bleeding or supratherapeutic INR", section on 'Serious/life-threatening bleeding'.)

Small doses (eg, 1 to 2 mg) of oral or IV vitamin K will reverse the maternal INR in approximately six hours or more, so we recommend giving this as well, but the fetal INR will not fully reverse. Though maternal administration of vitamin K reduces the risk of maternal bleeding, it leaves a high risk of fetal/neonatal hemorrhage. Vitamin K is routinely given to newborns shortly after birth to prevent vitamin K deficiency bleeding. (See "Overview of vitamin K", section on 'Vitamin K-deficient bleeding in newborns and young infants' and "Overview of the routine management of the healthy newborn infant", section on 'Vitamin K'.)

If the woman is on therapeutic LMWH and emergency delivery is necessary, protamine should be considered, bearing in mind that protamine will only partially reverse the anticoagulant effect of LMWH. The dose of protamine should be discussed with the obstetric anesthesiologist. (See "Heparin and LMW heparin: Dosing and adverse effects", section on 'Reversal'.)

If the woman is on IV UFH, cessation of the infusion will rapidly reverse the anticoagulant effect. Protamine is only required if the woman has major bleeding complications.

Residual anticoagulation or dual antiplatelet therapy at the time of labor or delivery may preclude use of neuraxial analgesia/anesthesia. Parenteral analgesia for labor and anesthesia for cesarean delivery are discussed separately. (See 'Anesthesia concerns' above and "Pharmacologic management of pain during labor and delivery" and "Anesthesia for cesarean delivery" and "Anesthesia for cesarean delivery", section on 'General anesthesia'.)

POSTPARTUM MANAGEMENT — Postpartum management of antithrombotic therapy is aimed at minimizing thrombotic and bleeding complications. Aspirin, low molecular weight heparin (LMWH), unfractionated heparin (UFH), and vitamin K antagonist (VKA) are all compatible with breastfeeding. (See "Use of anticoagulants during pregnancy and postpartum", section on 'Breastfeeding'.)

For patients with a bioprosthetic valve with no indication for anticoagulation, low-dose aspirin is generally continued in the postpartum period and for life.

For patients with a mechanical valve (or bioprosthetic valve requiring anticoagulation), the timing of neuraxial catheter removal and resumption of anticoagulation is carefully considered/selected to balance bleeding and thrombotic risks. Neuraxial catheters may be removed no sooner than 12 hours after the last dose of prophylactic LMWH and before resumption of anticoagulant therapy. (See "Neuraxial anesthesia/analgesia techniques in the patient receiving anticoagulant or antiplatelet medication", section on 'LMWH thromboprophylaxis'.)

In the absence of significant bleeding, for females with mechanical valves, anticoagulation should be resumed shortly after delivery. The timing of resumption of anticoagulation is selected by balancing the risk of incisional or uterine bleeding and spinal epidural hematoma (for those who received neuraxial analgesia or anesthesia) versus the risk of thromboembolic complications, including prosthetic valve thrombosis.

Intravenous (IV) UFH or subcutaneous (SC) LMWH should be resumed within four to six hours after delivery (and at least four hours after neuraxial catheter removal) if there are no bleeding complications [10]. This approach is in line with guidance from the United Kingdom National Institute for Health and Care Excellence [14].

-We suggest starting an infusion of UFH at a usual dose with no bolus and gradually increasing the dose to achieve therapeutic anticoagulation over 24 to 48 hours if a vaginal delivery and 48 to 72 hours if a cesarean delivery. Some clinicians have raised concern that overlap of therapeutic dose LMWH with the recommenced warfarin, especially after cesarean delivery, may contribute to postpartum bleeding complications. Use of IV UFH postpartum may allow more rigorous control of anticoagulation but may be impractical for service providers who are no longer familiar with the use of IV UFH.

-We suggest a prophylactic dose of SC LMWH initially and then half a therapeutic dose (eg, enoxaparin 0.75 mg/kg) based upon the patient's postpartum weight 12 hours later and continued as twice-daily dosing (eg, enoxaparin 0.75 mg/kg every 12 hours).

Due to concern that postpartum hemorrhagic complications may occur when therapeutic IV UFH or LMWH is overlapped with warfarin, warfarin should not be reintroduced until day 5 to 7. Either the heparin infusion or the LMWH is discontinued once the international normalized ratio (INR) is in the therapeutic range, although standard anticoagulation guidelines suggest continuing heparin until the INR has been therapeutic for 24 to 48 hours.

Low-dose aspirin is continued after delivery. (See "Antithrombotic therapy for mechanical heart valves".)

ANTITHROMBOTIC AGENTS — Our approach is based upon efficacy and safety data on anticoagulants in pregnant patients with mechanical heart valves. When therapeutic anticoagulation is required during pregnancy and postpartum, there is the risk of pregnancy-specific bleeding related to the placenta or to delivery. Antepartum hemorrhage (unexplained or due to placenta previa or placental abruption) appears to be increased in females with mechanical valves on therapeutic anticoagulation [15,16]. Postdelivery bleeding related to cesarean delivery, as well as vaginal and perineal trauma, may be increased. As such, detailed planning of anticoagulation management before, during, and after delivery is critical. (See "Use of anticoagulants during pregnancy and postpartum" and 'Peripartum management' above.)

The main options for long-term anticoagulation for a mechanical valve during pregnancy are vitamin K antagonist (VKA; eg, warfarin) and low molecular weight heparin (LMWH). Unfractionated heparin (UFH) is used as a last resort in settings in which LMWH is unavailable and the patient declines use of VKA. Maternal and fetal outcome estimates for various anticoagulation regimens in pregnant patients with mechanical valves are shown in the table (table 1). While VKA (eg, warfarin) is the most effective therapy to prevent mechanical prosthetic valve thrombosis and thromboembolism, warfarin use is associated with an increased risk of fetal anomalies and a high risk of late fetal loss, as discussed below. LMWH use is associated with low fetal risk but higher risk of maternal mortality and thromboembolism than with VKA. (See 'Vitamin K antagonist' below and 'Low molecular weight heparin' below.)

Vitamin K antagonist

Use — When VKA (eg, warfarin) is used during pregnancy, meticulous control is required, including close monitoring of the international normalized ratio (INR; eg, twice weekly or once weekly in some centers), patient education regarding dietary intake of vitamin K, and a dedicated prescriber adjusting the dose as needed.

When using VKA therapy for a mechanical prosthetic valve, the target INR varies with the type of valve, location of the valve (aortic versus mitral), and the presence of risk factors for thromboembolism, as discussed separately. (See "Antithrombotic therapy for surgical bioprosthetic valves and surgical valve repair", section on 'Thromboembolism' and "Antithrombotic therapy for mechanical heart valves", section on 'Approach to antithrombotic therapy'.)

Evidence — VKA is the safest anticoagulant option for the mother, but it increases the risk of congenital fetal anomalies, fetal loss, and fetal hemorrhagic complications.

VKA is the most effective therapy to prevent complications of valve thrombosis (including valve obstruction, thromboembolism, and maternal death), with a rate of pregnancy-related valve maternal thromboembolic complications of approximately 2 to 4 percent with contemporary valves [17,18]. The safety and efficacy of various anticoagulant regimens in pregnant patients with mechanical prosthetic heart valves were illustrated by a systematic review of the literature up to 2016 of 46 observational studies including 1307 pregnancies; maternal complications including maternal mortality (0.9 percent with VKA, 2 percent with sequential treatment [first trimester heparin followed by VKA], and 2.9 percent with LMWH) and thromboembolic events (2.7 percent with VKA, 5.8 percent with sequential treatment, and 8.7 percent with LMWH) were lowest with VKA [17]. A systematic review up to 2016 of 18 publications including 800 pregnancies reported a higher composite maternal risk (death, prosthetic valve failure, and systemic thromboembolism) of 16 percent with LMWH compared with VKA (5 percent) [19].

In contrast to the potential maternal benefit of VKA therapy, maternal VKA use is associated with fetal risk. VKA freely crosses the placenta and maternal VKA use is associated with a characteristic embryopathy with risk of fetal anomalies estimated at 5 to 10 percent (associated primarily with warfarin exposure during the first trimester) [17,18,20-23], risk of miscarriage (pregnancy loss before the 20th week of gestation; approximately 30 percent) [18,24], a high risk of late fetal loss (pregnancy loss at ≥20th week of gestation; approximately 10 percent), warfarin fetopathy with exposure after the first trimester, and fetal hemorrhagic sequelae [15,20,24,25]. The risk of both fetal anomalies and spontaneous miscarriage increases after week 5 [18].

Warfarin exposure early in pregnancy can cause a specific embryopathy affecting cartilage and bone (chondromalacia punctata, with stippled epiphyses and nasal and limb hypoplasia). The estimated incidence is 5 to 10 percent, although reported ranges vary [18,20-23]. In one review, the risk of major anomalies was 4.8 percent when VKA therapy was discontinued by eight weeks gestation as compared with 1.4 percent in the general population [26]. A cohort study of phenprocoumon demonstrated that cessation before five completed weeks of gestation resulted in no increased risk of congenital disorders, but that if the VKA was continued after seven weeks, the risk of congenital disorders was 10.8 percent compared with 2.3 percent in unexposed pregnancies. Furthermore, the risk of miscarriage was also increased (38 percent compared with 17.5 percent in the unexposed pregnancies, and the hazard ratio of miscarriage was 1.12 for every additional week of exposure) [18]. In the ROPAC study, the rate of miscarriage was 28.6 percent with VKA compared with 9.2 percent with heparin, and the rates for late fetal loss were 7.1 and 0.7 percent, respectively [24]. In a systematic review, the composite fetal risk (miscarriage, death, congenital abnormalities) was 39 percent with VKA compared with 13 percent with LMWH and 23 percent with sequential LMWH and VKA [19].

Fetal warfarin exposure after the first trimester appears to increase the risk of central nervous system defects, presumably from microhemorrhages in neuronal tissues; five case reports have described massive fetal intracranial hemorrhage associated with maternal warfarin use [27,28]. The fetal INR runs at a higher level than the maternal INR due to fetal hepatic immaturity, which contributes to the risk of hemorrhagic complications. (See "Use of anticoagulants during pregnancy and postpartum", section on 'Warfarin teratogenicity'.)

Warfarin is also associated with a high rate of late fetal loss. In one review, after exclusion of spontaneous miscarriage, 12 percent of the 596 pregnancies in females taking warfarin throughout pregnancy ended in a fetal death [20]. Additional data report a similar high perinatal death rate associated with warfarin [15].

A dose-dependent effect of warfarin on fetal embryopathy and fetal loss has been reported, with warfarin ≤5 mg/day having lower rates of fetal complications than warfarin >5 mg/day [19,21,22,29,30], although fetal warfarin syndrome has been reported with warfarin ≤5 mg/day [30,31]. The clinical relevance of these findings is limited since the dosing is adjusted to achieve adequate anticoagulation (as measured by the INR) for each patient with a mechanical valve [32]. (See "Antithrombotic therapy for mechanical heart valves" and "Warfarin and other VKAs: Dosing and adverse effects".)

Low molecular weight heparin

Use — When therapeutic weight-adjusted LMWH is used (eg, initial dose of enoxaparin 1 mg/kg every 12 hours), it is recommended that peak anti-factor Xa (three to four hours after subcutaneous [SC] injection) be measured at one to two weekly intervals and the LMWH dose adjusted accordingly [16,33]. We use higher targets (1.0 to 1.2 units/mL) for mechanical valves in the mitral position and lower targets (0.8 to 1.0 units/mL) for mechanical aortic valve replacements. Peak anti-Xa levels should be <1.5 units/mL to avoid excessive anticoagulation and increased risk of bleeding. We also suggest monitoring anti-Xa trough levels (target ≥0.6 units/mL [8]). The 2014 American Heart Association/American College of Cardiology (AHA/ACC) valve guidelines recommend maintaining anti-Xa activity between 0.8 and 1.2 units/mL [1]. The 2023 British Society for Haematology guideline for anticoagulant management of pregnant individuals with mechanical valves recommends a peak anti-Xa target of 1.0 to 1.4 units/mL taken three to four hours following a twice daily LMWH dose [7].

Evidence — LMWH does not cross the placenta and does not have known harmful effects on the fetus. When heparin is used, LMWHs are the preferred treatment modality over UFH given their improved pharmacokinetics and bioavailability, their reduced side effect profile, and apparent lower rates of associated valve thrombosis [15,33,34]. LMWH has several advantages over UFH: It has a more predictable attainment of therapeutic level of anticoagulation, appears to have less effect on bone, and is associated with less bleeding and thrombocytopenia. (See "Heparin and LMW heparin: Dosing and adverse effects".)

Increasingly, pregnant patients are choosing to use LMWH during pregnancy after counseling about the maternal and fetal effects of various anticoagulant options [3,15,16,33-36]. Evidence suggests therapeutic LMWH may be an acceptable alternative to warfarin for many females as they balance the slightly higher level of thrombotic risk against improved fetal outcomes compared with warfarin [15,33,34,36]. In a systematic review, live birth rates were 92 percent with LMWH, 80 percent with sequential therapy (first trimester heparin followed by VKA), and 65 percent with VKA [17]. The risk of thromboembolic complications with LMWH use during pregnancy has been reported as 12 percent [17,35], though it may be lower with careful anti-Xa monitoring to target four-hour peak level of 1.0 to 1.2 units/mL and adequate trough activity. Use of LMWH at subtherapeutic dose regimens or poor adherence accounts for many, but not all, reported cases of valve thromboses or thromboembolism [20,33,35,36].

There are no randomized trials of LMWH use versus warfarin or UFH in pregnant patients with mechanical heart valves. A review of early publications reporting LMWH use in pregnant patients with mechanical heart valves (16 studies, 1996 to 2003) found thromboembolic complications occurred in 12.3 percent of 81 pregnancies [35]. When only females who received therapeutic LMWH were included, thromboembolism occurred in one of 37 pregnancies (2.7 percent) [35]. A second review raised concerns with a 22 percent [37] rate of thrombotic events in 76 pregnancies reported in 23 papers (1996 to 2005) [37]. Publication bias in part contributes to these rates, with the higher rate of thromboembolic events in the second review due to inclusion of a greater number of single case reports [35,37]. In several cases, thrombotic events were related to use of subtherapeutic doses of LMWH, suboptimal anti-Xa activity, and poor patient adherence [15,33,35].

Studies suggest the rate of thromboembolic events in pregnant patients with mechanical valves may be lower when therapeutic LMWH is managed with intensive anti-Xa monitoring, followed by dose adjustment [15,16,33,34,36]. In these small cohorts, a total of 109 pregnancies treated with twice-daily, dose-adjusted therapeutic LMWH have been reported. These include 14 pregnancies (13 pregnancies in one series [15] plus one pregnancy in another report [16]) in which warfarin was the predominant therapy. In the remaining 95 pregnancies, thromboembolic complications occurred in 9.5 percent of females with mechanical valves treated with therapeutic range LMWH. In eight of the nine pregnancies with thromboembolic complications, there was subtherapeutic dosing, poor adherence, or low anti-Xa activity. There was one maternal death related to valve thrombosis [36]. These data suggest that if therapeutic LMWH with dose adjustment to maintain anti-Xa activity of 1.0 to 1.2 units/mL is achieved, the risk of thromboembolic complications is low, probably less than 5 percent.

When translated into clinical practice, however, the failure rate is likely to be on the order of 5 to 10 percent due to issues such as patient adherence. In a systematic review, studies that used subtherapeutic, unadjusted, or unclear anticoagulation regimens were excluded; VKA was associated with the fewest maternal complications but also the fewest live births [17]. In the ROPAC study, there were 10 (4.7 percent) thrombosed mechanical valves, and five of these occurred in the first trimester following a switch to some form of heparin [24]. In a systematic review of studies of pregnant patients with mechanical heart valves treated with LMWH, pregnant patients experienced both thrombotic and bleeding complications with anti-Xa activity in the target range [38]. This finding highlights that anti-Xa monitoring does not completely prevent the risks of valve thrombosis and obstetric bleeding.

In later reports of therapeutic LMWH in females with mechanical heart valves, there appears to be an increased rate of antepartum and postpartum bleeding complications. Of the 95 pregnancies summarized above, there were seven antepartum hemorrhages (secondary to placental abruption, placenta previa, or unexplained), nine postpartum hemorrhages, four bleeds related to cesarean delivery, and four other hemorrhagic complications such as epistaxis [15,16,33,34,36]. In a single-center study of 32 pregnancies from 2003 to 2011, the only maternal death was from an intracerebral hemorrhage in a woman managed with LMWH throughout pregnancy [39]. In the ROPAC study, the rate of hemorrhage in those with mechanical valves was 23.1 percent compared with 5.1 percent in those with bioprosthetic valves [24].

Unfractionated heparin

Use — In practice, UFH use for anticoagulation for a mechanical valve is generally confined to intravenous (IV) administration at times when rapid reversal of the anticoagulant effect may be required (eg, pre- or postpartum).

UFH is a possible option for long-term anticoagulation for a mechanical valve only in clinical settings in which warfarin is not an option (due to risks and/or patient preference) and LMWH is unavailable due to resource limitations:

During the first trimester, dose-adjusted continuous IV infusion of UFH (with targeted activated partial thromboplastin time [aPTT] 2 to 2.5 times control) is a potential option, though the efficacy and safety of this treatment over weeks are uncertain, given limited efficacy, difficult monitoring, and the risk of infection.

During the second and third trimesters, dose-adjusted SC administration (with targeted aPTT 2 to 2.5 times control) is a potential option (last resort) when LMWH is unavailable only if the mother declines to take warfarin. The efficacy and safety of this treatment over weeks are uncertain, and use of SC UFH in this setting is controversial and not endorsed by some experts [1].

Given the adverse effect of UFH on bone mineral density (BMD), we suggest calcium supplementation (1.2 g/day) during pregnancy and postpartum for females taking UFH to ensure that the recommended daily allowance is achieved. (See "Drugs that affect bone metabolism", section on 'Heparin'.)

Evidence — UFH does not cross the placenta and does not have direct harmful effects on the fetus. However, the risk of thromboembolic complications is high in pregnant patients with mechanical valves when UFH is used throughout pregnancy (eg, 11.2 percent) or during the first trimester (eg, 5.8 percent) [17,20], and thus use of SC UFH during pregnancy for prosthetic valves is not recommended by some major society guidelines [1]. Poor adherence and subtherapeutic regimens contribute to this high rate of valve thrombosis, but thromboembolic complications can occur with therapeutic SC heparin [40]. Maternal thromboembolic complications requiring valve replacement or resulting in maternal death may contribute to fetal losses associated with UFH reported in some studies, and the magnitude of risk is uncertain given the limited number of cases [17,20]. IV UFH (with targeted aPTT 2 to 2.5 times control) may provide better protection against thromboembolism than SC UFH, but its efficacy and safety over weeks are uncertain. Long-term UFH may also reduce BMD.

UFH is a large molecule that does not cross the placenta and therefore does not have any known harmful effects on the fetus. Published data on the use of UFH throughout pregnancy in females with mechanical valves are limited [20,40]. There are more data regarding staged therapy, with the use of UFH in the first trimester, followed by VKAs [20,41-44]. (See "Use of anticoagulants during pregnancy and postpartum", section on 'Unfractionated heparin'.)

In the systematic review described above, thromboembolic complications were more common when UFH was used throughout pregnancy than when UFH was used only during the first trimester, which in turn was higher than in females who took warfarin throughout pregnancy (8.7, 5.8, and 2.7 percent, respectively) [17,20]. Further comparisons with UFH are limited by the use of prophylactic- rather than therapeutic-dose UFH in some cases and uncertainty about the intensity of monitoring aPTT [20,40,42].

High-dose SC or IV UFH (eg, mid-dose target aPTT at least two times control) may provide better protection against thromboembolism than low SC doses, but even with this approach, concerning rates of thromboembolic complications have been reported [40,44]. In addition, with the advent of LMWH treatment for thromboembolism, there is declining clinician familiarity with IV UFH, and IV UFH is associated with risk of infection from the prolonged use of IV catheters [1].

Months of UFH may cause bone loss with reduced BMD in many pregnant patients and osteoporotic fractures in a significant minority of these patients (2.2 percent in one series) [45]. Although recovery of BMD occurs postpartum after heparin is discontinued, it is unclear if recovery is complete.

Aspirin

Use — Indications for low-dose aspirin (75 to 100 mg/day; eg, 81 mg/day) during pregnancy in patients with bioprosthetic or mechanical valves are discussed above. (See 'Bioprosthetic valve management during pregnancy' above and 'Mechanical valve management during pregnancy' above and 'Approach for planned delivery' above.)

Evidence — Data on the safety and efficacy of low-dose aspirin in pregnant patients with prosthetic heart valves are limited. However, low-dose aspirin has been studied in pregnant patients with other indications with a generally acceptable safety profile. (See "Safety of rheumatic disease medication use during pregnancy and lactation", section on 'Aspirin (low dose)'.)

In nonpregnant patients with bioprosthetic valves, limited observational data are available on the use of aspirin. (See "Antithrombotic therapy for surgical bioprosthetic valves and surgical valve repair", section on 'Intermediate- and long-term antithrombotic therapy'.)

Scant data are available on the efficacy and safety of aspirin therapy in addition to anticoagulation in pregnant patients with mechanical valves. A study of data from ROPAC included 212 patients with mechanical valves treated with anticoagulants, of which only 13 also used aspirin during the second and third trimesters [24]. Mechanical valve thrombosis was nominally but not significantly less frequent in the 13 patients treated with concurrent aspirin compared with the 199 patients not treated with aspirin (0.0 versus 2.5 percent, p = 1.00). Hemorrhagic events were significantly more frequent among patients taking concurrent aspirin (61.6 versus 20.6); the anticoagulant (VKA or heparin) taken with aspirin was not specified. This evidence is not sufficient to adequately establish the risks and benefits of concurrent aspirin therapy in pregnant patients with mechanical valve treated with anticoagulation.

In nonpregnant patients with mechanical heart valves, meta-analyses of randomized trials found that the addition of low-dose aspirin to warfarin reduced the risk of mortality as well as the risk of thromboembolism and increased the risk of major hemorrhage compared with anticoagulation alone. (See "Antithrombotic therapy for mechanical heart valves", section on 'Selective use of aspirin'.)

Direct oral anticoagulants — Direct oral anticoagulants (DOACs, also known as non-vitamin K oral anticoagulants [NOACs]), including direct thrombin inhibitors (eg, dabigatran) and direct factor Xa inhibitors (eg, rivaroxaban, apixaban, and edoxaban), should not be considered alternatives to therapy with warfarin or heparin in patients with mechanical heart valves (during or outside of pregnancy). Adverse events have been observed in some animal studies, and safety data in pregnant patients are lacking. A US Food and Drug Administration safety communication specifically notes that dabigatran is contraindicated in patients with mechanical heart valves based upon the results of the RE-ALIGN trial. (See "Antithrombotic therapy for mechanical heart valves", section on 'Long-term anticoagulation'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Cardiac valve disease" and "Society guideline links: Anticoagulation in pregnancy" and "Society guideline links: Management of cardiovascular diseases during pregnancy".)

SUMMARY AND RECOMMENDATIONS

Management during pregnancy

Bioprosthetic valve – For patients with a bioprosthetic (surgical or transcatheter) valve, we suggest continuing low-dose aspirin (75 to 100 mg/day; eg, 81 mg/day) during pregnancy (Grade 2C). (See 'Bioprosthetic valve management during pregnancy' above and 'Aspirin' above and "Antithrombotic therapy for surgical bioprosthetic valves and surgical valve repair", section on 'Approach for surgical bioprosthetic valves'.)

Mechanical valve – Pregnant patients with mechanical prosthetic valves should be fully informed about the importance of therapeutic anticoagulation throughout pregnancy and the maternal and fetal risks associated with each anticoagulant regimen. Shared decision-making involving the patient is essential. (See 'Mechanical valve management during pregnancy' above.)

-The main options for long-term anticoagulation for a mechanical valve during pregnancy are vitamin K antagonist (VKA; eg, warfarin) and low molecular weight heparin (LMWH). Unfractionated heparin (UFH) is used only as a last resort in settings in which LMWH (or anti-Xa monitoring) is unavailable and the patient declines use of VKA. While VKA (eg, warfarin) is the most effective therapy to prevent mechanical prosthetic valve thrombosis and thromboembolism, VKA use is associated with an increased risk of fetal anomalies (particularly with warfarin doses >5 mg/day during the first trimester) and a high risk of late fetal loss. LMWH use is associated with low fetal risk but higher risk of maternal mortality and thromboembolism than with VKA (table 1). (See 'Antithrombotic agents' above.)

-For pregnant patients with mechanical prosthetic valves, we recommend low-dose aspirin (75 to 100 mg/day; eg, 81 mg/day) along with whichever anticoagulant is selected (VKA, LMWH, or UFH) (Grade 1B). Of note, there is variation in clinical practice in this setting, with some clinicians administering low-dose aspirin only during periods of heparin anticoagulation (LMWH or UFH). (See 'Aspirin' above and "Antithrombotic therapy for mechanical heart valves", section on 'Selective use of aspirin'.)

For mechanical valve with risk factor for valve thrombosis – For patients with a mechanical prosthetic valve with one or more risk factors for prosthetic valve thrombosis/thromboembolism (eg, mechanical mitral valve, mechanical tricuspid valve, atrial fibrillation or flutter, previous thromboembolic complications, or multiple mechanical heart valves), we suggest continuing VKA (eg, warfarin) with close international normalized ratio (INR) monitoring throughout pregnancy until 36 weeks (algorithm 1) (Grade 2C). In making this recommendation, we are placing high value on reducing maternal risk. Pregnant patients with mechanical valves who place a high value on minimizing fetal risk may reasonably choose dose-adjusted twice-daily subcutaneous (SC) LMWH (target anti-Xa level 1.0 to 1.2 units/mL for mitral valve and 0.8 to 1.0 units/mL for aortic valve replacements at four to six hours postdose, with trough activity checked as well) during the first trimester. (See 'With risk factors for prosthetic valve thrombosis' above.)

For mechanical valve without risk factors for prosthetic valve thrombosis – For pregnant patients with mechanical valves without risk factors for prosthetic valve thrombosis, anticoagulant selection for the first trimester may or may not differ from that chosen for later trimesters (see 'Without risk factors for prosthetic valve thrombosis' above):

-During the first trimester – For patients with mechanical valves without one or more of the above risk factors for prosthetic valve thrombosis or thromboembolism (algorithm 1):

-If baseline VKA dose is relatively low (warfarin dose ≤5 mg/day, phenprocoumon ≤3 mg/day, or acenocoumarol ≤2 mg/day), the main anticoagulation options are continuing VKA with close INR monitoring throughout the first trimester or dose-adjusted SC LMWH from 5 to 12 weeks (dosed twice daily; target anti-Xa level 1.0 to 1.2 units/mL for mitral valve and 0.8 to 1.0 units/mL for aortic valve replacement at four to six hours post-dose, with trough activity ≥0.6 units/mL). If the patient declines VKA use and LMWH with appropriate monitoring is unavailable, UFH is an option of last resort.

-For patients whose baseline VKA dose is high (defined as warfarin >5 mg/day, phenprocoumon >3 mg/day, or acenocoumarol >2 mg/day), we suggest switching to dose-adjusted twice-daily SC LMWH throughout the first trimester (Grade 2C).

-During the second and third trimesters – For most females with mechanical valves, we suggest VKA (adjusted to INR goal) during the second and third trimesters until 36 weeks (Grade 2C). In making this recommendation, we are placing high value on reducing maternal risk. If the mother chooses to avoid the fetal risk associated with VKA therapy, therapeutic SC LMWH is a reasonable alternative. SC LMWH is dosed twice daily with the dose adjusted to achieve target anti-Xa activity of 1.0 to 1.2 units/mL for mitral valve prosthesis and 0.8 to 1.0 units/mL for aortic valve prosthesis at four to six hours postdose and ensuring adequate trough activity as well.

Peripartum management

For patients with a bioprosthetic valve receiving aspirin as the sole antithrombotic therapy, cessation of aspirin prior to delivery is not required if no other antithrombotic agents will be administered during the peripartum period. (See 'Aspirin' above and "Neuraxial anesthesia/analgesia techniques in the patient receiving anticoagulant or antiplatelet medication", section on 'Aspirin and other nonsteroidal antiinflammatory drugs'.)

For patients with a mechanical valve (or with a bioprosthetic valve requiring anticoagulation), changes in antithrombotic therapy are required as the time for delivery approaches to minimize the risks of maternal hemorrhage (including the risk of spinal epidural hematoma [SEH] with neuraxial anesthesia/analgesia) and fetal hemorrhage. A plan for anticoagulation in labor/peripartum should be agreed to by obstetricians, anesthesiologists, and hematologists and documented clearly. The risks of valve thrombosis and obstetric hemorrhage as well as the desire to use regional anesthesia need to be balanced and the patient fully informed of the rationale for the individualized plan. (See 'Approach for planned delivery' above.)

Postpartum management - In the absence of significant bleeding, anticoagulation for females with mechanical valves should be resumed shortly after delivery. The timing of resumption of anticoagulation is selected by balancing the risk of incisional or uterine bleeding and SEH (for those who received neuraxial analgesia/anesthesia) versus the risk of thromboembolic complications including prosthetic valve thrombosis. (See 'Postpartum management' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Robyn A North, MBChB, PhD, FRACP, Beverley Hunt, MD, FRCP, FRCPath, William Gaasch, MD, Catherine Otto, MD, and Charles Lockwood, MD, MHCM, who contributed to earlier versions of this topic review.

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Topic 8126 Version 27.0

References

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