Perioperative blood management: Strategies to minimize transfusions

INTRODUCTION — This topic reviews the general approach to perioperative blood management, including strategies to avoid or minimize transfusion of blood components during surgical and other invasive procedures.

Separate topics discuss specific strategies for blood management during cardiac surgery with cardiopulmonary bypass (CPB). (See "Blood management and anticoagulation for cardiopulmonary bypass" and "Achieving hemostasis after cardiac surgery with cardiopulmonary bypass".)

Indications, risks, and decision-making for intraoperative transfusion of specific blood components (eg, red blood cells [RBCs], fresh frozen plasma [FFP], platelets). Cryoprecipitate and administration of clotting factors (eg, fibrinogen concentrate, prothrombin complex concentrates, recombinant factor VIIa [rFVIIa]) are discussed separately. (See "Intraoperative transfusion and administration of clotting factors".)

GOALS OF PATIENT BLOOD MANAGEMENT — Patient blood management (PBM) is a patient-centered, systematic, evidence-based approach to improve patient outcomes by managing and preserving a patient’s own blood, while promoting patient safety and empowerment [1-7].

Managing anemia and reducing the risk of anemia are intended to reduce transfusions of red blood cells (RBCs) and possibly other blood components, in turn reducing risks of anemia, transfusion reactions and other transfusion complications [4,8,9]. This patient-centered multimodality and multidisciplinary approach focuses on clinical outcomes rather than use of blood components [6]. Cost saving is a side benefit.

●One retrospective study involving 25 hospital sites in Canada demonstrated significant reductions in blood component use over an 18-year period from 2002 to 2020 [10]. For example, the need for RBC transfusion was reduced from 25 to 0.4 percent in knee replacement surgery and from 60 to 27 percent in coronary artery bypass (CABG) surgery.

●Another retrospective study in Australia estimated substantial cost savings after implementation of preoperative screening and management of anemia and suboptimal iron stores in patients undergoing elective colorectal surgery [11].

Techniques and strategies for optimal PBM span the entire perioperative period from preoperative assessment until discharge from the hospital (table 1) [4,12].

For major or complex surgical procedures with a known high risk of significant blood loss (>500 to 1000 mL), advance discussions with the surgical team, a hemostasis expert, and/or the patient's primary clinician may identify opportunities to implement preoperative or intraoperative measures to avoid allogeneic transfusion, such as delay of an elective procedure to treat certain causes of anemia, preoperative autologous blood donation, intraoperative blood salvage, acute normovolemic hemodilution (ANH), or use of antifibrinolytic agents or other hemostatic products [6,13]. (See 'Preoperative strategies' below and 'Intraoperative strategies' below and "Intraoperative transfusion and administration of clotting factors", section on 'Use of clotting factors'.)

Since the COVID-19 pandemic has resulted in many regional blood inventory shortages due to decreased donations, perioperative PBM is critically important to aid in balancing supply and demand for blood components [4,14-17].

A comprehensive discussion of other strategies to minimize blood loss is presented separately. (See "Approach to the patient who declines blood transfusion", section on 'Minimize blood loss'.)

PREOPERATIVE STRATEGIES — The preanesthetic consultation provides an opportunity to assess and address risks for bleeding and to evaluate possible interventions to minimize the need for transfusions (table 1) [4,18-21]. Certain disorders (eg, anemia), surgical procedures (eg, cardiac surgery, liver transplantation), and medications that affect hemostasis (anticoagulants and antiplatelet agents) are associated with increased potential for bleeding and transfusion.

Elective surgical procedures — It may be appropriate to postpone an elective procedure when there is a reversible cause of anemia or coagulopathy that can be corrected in a reasonable period of time (algorithm 1).

Selective laboratory testing

●Hemoglobin or complete blood count – A baseline hemoglobin measurement (typically a component of a complete blood count [CBC]) is obtained in patients undergoing selected major surgery surgical procedures that have significant expected blood loss (procedures with >10 percent chance of needing a transfusion or >500 mL blood loss). Preoperative anemia due to a known underlying condition should be evaluated and appropriately managed before surgery unless the scheduled procedure is minor. (See 'Treatment of anemia' below.)

Ideally, a baseline CBC is obtained approximately four weeks prior to scheduled major elective surgery. This allows adequate time for appropriate treatment of anemia, such as replacement of iron stores in individuals with iron deficiency [22]. In some cases, elective surgery may need to be delayed (algorithm 1). (See "Indications and hemoglobin thresholds for RBC transfusion in adults", section on 'Hospital-wide oversight programs/patient blood management'.)

By contrast, a CBC or hemoglobin measurement is not necessary for patients undergoing minor surgery unless the history suggests anemia. (See "Preoperative medical evaluation of the healthy adult patient", section on 'Complete blood count'.)

●Screening tests for bleeding disorders – For patients with a personal history, family history, or physical examination suggesting the presence of a bleeding disorder, appropriate screening tests should be obtained. These often include, but are not limited to, a platelet count and screening tests of coagulation (prothrombin time [PT] with international normalized ratio [INR] and activated partial thromboplastin time [aPTT]) [18,23,24]. In some cases, liver function tests or tests of kidney function (creatinine) may also be obtained. (See "Approach to the adult with a suspected bleeding disorder".)

If indicated, such screening should be done early enough to allow time for diagnosis and treatment of causes of hemostatic abnormalities. A hematology consultation is typically necessary. In selected cases (eg, patients with significant prior bleeding episodes or recent decrease in hemoglobin level or need for transfusion), it is appropriate to obtain a consultation even if screening tests are normal. However, we do not obtain screening tests of coagulation unless a bleeding disorder is suspected, in accord with the recommendations of the American Society of Anesthesiologists [25], the British Committee for Standards in Hematology [26], and the European Society of Anaesthesia [27]. (See "Preoperative assessment of bleeding risk", section on 'Laboratory testing'.)

Routine screening for thrombocytopenia is not indicated in patients without a suspected bleeding disorder, as isolated thrombocytopenia is rare and usually identified before preoperative testing [28]. (See "Preoperative assessment of bleeding risk", section on 'Avoid routine testing in unselected individuals'.)

●Testing for individuals receiving anticoagulants – Individuals receiving anticoagulants typically have recent laboratory testing available that should be reviewed (eg, PT/INR for those on warfarin, creatinine for those on a dabigatran or a direct factor Xa inhibitor). This information may factor into decisions regarding the preoperative timing of anticoagulant discontinuation. (See "Perioperative management of patients receiving anticoagulants".)

●Typing and crossmatching tests – Typing and crossmatching tests to ensure availability of appropriate blood components are necessary before procedures with large expected blood loss; the blood bank or transfusion medicine service should be notified of the approximate number of units that are likely to be required based on known blood loss associated with the specific procedure as well as the potential for greater than average blood loss that may occur or may be poorly tolerated in certain patients (eg, those with comorbidities).

Treatment of anemia — Anemia is a highly prevalent risk factor for morbidity and mortality in surgical patients and is independently associated with increased risk of transfusion [1,20,21,29-33]. Chronic anemia can be a marker for other comorbidities in addition to being a direct cause of morbidity and mortality [34]. (See "Indications and hemoglobin thresholds for RBC transfusion in adults", section on 'Impact of anemia on morbidity and mortality'.)

Depending on the cause and degree of anemia, the urgency of the procedure, and the expected amount of blood loss and other risk factors, surgery may be postponed to diagnose the cause of anemia and provide treatment when feasible, in order to minimize the risk of perioperative transfusion of red blood cells (RBCs) (algorithm 1) [4,19-21,29-31,35-39].

While many patients with preoperative anemia have iron deficiency or anemia of chronic disease/anemia of inflammation, other causes of anemia include folate and vitamin B12 deficiencies [31]. For patients who have unknown or complex causes of anemia, input is sought from a consultant with expertise in anemia management. (See "Anemia of chronic disease/anemia of inflammation", section on 'ESAs' and "Approach to the child with anemia" and "Diagnostic approach to anemia in adults".)

Iron deficiency anemia — Iron deficiency anemia is a surprisingly common condition across various surgical and other patient populations [1,4,20,30,31,33,40-43]. Even among patients whose anemia is attributed to other causes (eg, chronic kidney disease or inflammation), some degree of iron deficiency may be present. Individuals with iron deficiency should be treated with iron rather than transfusion, unless the anemia is extremely severe and there is risk of organ ischemia, as discussed separately. If iron is administered, sufficient time should be allowed for effective treatment of anemia before surgery (typically two to four weeks for partial correction and six to eight weeks for full correction). In individuals with unexplained iron deficiency, determination of the underlying cause is an essential part of management. (See "Causes and diagnosis of iron deficiency and iron deficiency anemia in adults" and "Treatment of iron deficiency anemia in adults".)

Oral iron replacement can be initiated in an iron-deficient patient if at least four to six weeks of time is available before planned surgery. Intravenous (IV) iron is an option if there is less than four to six weeks until semi-elective surgery, and for patients who cannot tolerate oral iron or do not have a response (eg, due to poor absorption) [20,21,30,33,35,39,44-46]. In this setting, IV iron can replenish body iron stores more rapidly and effectively than oral iron therapy; however, time is still required for the iron to be incorporated into developing RBCs and for the hemoglobin level to increase, and available trials have not been adequately powered to determine whether rates of transfusion are lower [31,33,43,46-49]. Details regarding decision-making and treatment are discussed separately. (See "Treatment of iron deficiency anemia in adults", section on 'Perioperative'.)

Use of erythropoietin

●Indications – Erythropoietin (EPO) can increase RBC production and increase the hemoglobin level, potentially reducing patients' exposures to allogeneic transfusion [31]. Administration of EPO typically should include supplemental iron to avoid functional iron deficiency that may occur in face of increased erythropoiesis.

EPO for treatment of anemia can be used in the following settings for scheduled surgical procedures [1]:

•For patients with anemia of chronic disease/anemia of inflammation undergoing a scheduled major noncardiac surgical procedure with expected blood loss >500 mL if hemoglobin is <12 g/dL [50]. Clinical judgment is used for patients with hemoglobin levels between 12 and 13 g/dL. (See "Anemia of chronic disease/anemia of inflammation".)

•For patients with anemia of chronic disease/anemia of inflammation undergoing cardiac surgery if hemoglobin <13 g/dL. Our approach is consistent with guidelines from the European Association for Cardio-Thoracic Surgery (EACTS), the European Association of Cardiothoracic Anaesthesiology (EACTA), and the Society of Cardiovascular Anesthesiologists, which recommend consideration of preoperative EPO administration with concomitant IV iron for anemic cardiac surgical patients, even if iron deficiency or iron deficiency anemia is absent [33,38,51]. (See "Preoperative evaluation for anesthesia for cardiac surgery", section on 'Anemia'.)

•For patients with anemia of chronic kidney disease (CKD), especially those receiving dialysis. (See 'Anemia associated with chronic kidney disease' below and "Treatment of anemia in patients on dialysis", section on 'Erythropoiesis-stimulating agents (ESAs)' and "Treatment of anemia in nondialysis chronic kidney disease", section on 'Erythropoiesis-stimulating agents'.)

•For patients for whom blood transfusion is not an option, as described separately. (See "Approach to the patient who declines blood transfusion", section on 'Erythropoiesis-stimulating agents (ESAs/EPO)'.)

Our general approach does not take the place of the judgment of the surgeon, anesthesiologist, internist, nephrologist, or hematologist regarding likelihood of avoiding transfusion and the risks and benefits of EPO administration for an individual patient.

●Dose – We typically begin EPO therapy three weeks before an elective procedure and provide three injections of 40,000 units or 300 to 600 units/kg of epoetin alfa once weekly, together with supplemental iron to avoid functional iron deficiency. If less than three weeks is available, we still administer EPO prior to the surgical procedure as it may still provide benefit.

●Adverse effects – Potential adverse effects of EPO include venous thromboembolism, hypertension, and possible adverse outcomes in patients with cancer being treated with curative intent, and it is reasonable to avoid EPO in individuals with severe uncontrolled hypertension or those with cancer receiving chemotherapy with curative intent. (See "Approach to the patient who declines blood transfusion", section on 'Erythropoiesis-stimulating agents (ESAs/EPO)' and "Role of erythropoiesis-stimulating agents in the treatment of anemia in patients with cancer".):

●Supporting evidence – There is significant heterogeneity among published studies with respect to dosing and timing of preoperative EPO administration, the presence, cause, and severity of preoperative anemia and/or iron deficiency, whether iron therapy was concomitantly administered, and the types of surgical procedures studied [31]. Data regarding benefits and risks of preoperative EPO administration are summarized as follows:

•A 2020 meta-analysis of randomized trials that included 1880 anemic patients (hemoglobin <13 g/dL for males or <12 g/dL for nonpregnant females) undergoing noncardiac surgery (primarily orthopedic, gastrointestinal, and gynecological surgery) compared administration of preoperative EPO plus iron therapy with placebo or standard of care (with or without iron) [52]. Preoperative EPO plus iron reduced the need for RBC transfusion (risk ratio [RR] 0.55, 95% CI 0.38-0.80).

•A 2019 meta-analysis of randomized trials comparing preoperative administration of EPO versus placebo (32 trials; 4750 patients, mostly orthopedic and cardiac surgery) found reduced blood transfusions in the EPO groups [53]. Decreased blood transfusions were seen in the entire population (RR 0.59, 95% CI 0.47-0.73; 28 trials), as well as the subgroups undergoing cardiac surgery (RR 0.55, 95% CI 0.47-0.73; nine trials) and major orthopedic surgery (RR 0.36, 95% CI 0.28-0.46; five trials). In addition, the EPO group had increased hemoglobin levels. There was no increase in the incidence of thromboembolic events with EPO.

•Another 2019 randomized trial in elective cardiac surgical patients with preoperative anemia or isolated iron deficiency noted reduced RBC transfusions from a median of one to zero units in those who received preoperative subcutaneous EPO administered together with IV iron, subcutaneous vitamin B12, and oral folic acid on the day before surgery, compared with those receiving placebo drugs (odds ratio [OR] 0.70, 95% CI 0.50-0.98) [54]. Post-hoc analysis of this trial confirmed that such "quadruple anemia treatment" significantly increased reticulocyte count on postoperative days 1,3, and 5 in patients with or without preoperative iron deficiency [55]. However, it is unknown whether administration of IV iron without EPO would have been equally effective in patients with iron deficiency, or whether giving vitamin B12 and folate conferred any additional benefit.

•A 2018 randomized trial in orthopedic surgical patients with hemoglobin 10 to 13 g/dL before hip or knee arthroplasty reported greater iron stores and improved erythropoiesis after treatment with weekly EPO plus concomitant administration of IV iron for three weeks before surgery, compared with treatment with EPO plus oral iron for the same period [48].

Anemia associated with chronic kidney disease — Management of patients with chronic kidney disease (CKD; with or without hemodialysis) may include iron and/or EPO. (See "Treatment of anemia in nondialysis chronic kidney disease", section on 'Treatment' and "Treatment of anemia in patients on dialysis", section on 'Treatment'.)

Details of therapy should be discussed with the patient's primary nephrologist. In particular, we try to avoid transfusion when possible in any patient on a transplant waiting list, as transfusion-induced allosensitization to HLA antigens may affect transplant outcomes. However, transfusion should not be withheld from an individual awaiting a kidney transplant if indicated to treat more severe symptomatic anemia.

Preoperative autologous blood donation — Preoperative autologous donation has been declining and is only rarely used due to high wastage of the autologous units, increased risk of anemia, increased risk of needing allogeneic transfusion, expense, and inconvenience [56]. Occasionally, preoperative autologous donation is used upon request as a blood conservation option in individuals in relatively good health who are not anemic prior to undergoing surgical procedures with significant expected blood loss (≥500 to 1000 mL) [56]. Recombinant human EPO may be used as an adjunct [19]. Further discussion is available in a separate topic. (See "Surgical blood conservation: Preoperative autologous blood donation".)

Management of thrombocytopenia or platelet dysfunction

●Thrombocytopenia – For individuals with known thrombocytopenia, discussions with the surgeon and consulting hematologist or the patient's primary clinician should focus on determining a safe platelet count for the proposed procedure and appropriate interventions to raise the platelet count to a safe level if needed. (See "Platelet transfusion: Indications, ordering, and associated risks", section on 'Preparation for an invasive procedure'.)

For patients who are found to have a low platelet count, causes of thrombocytopenia are evaluated prior to elective surgery. Depending on the type and urgency of the surgical procedure and the cause and degree of thrombocytopenia, surgery may be postponed and/or therapy may be given to increase the platelet count before the procedure. Suggested platelet count thresholds for various common invasive procedures are discussed in a separate topic. (See "Platelet transfusion: Indications, ordering, and associated risks", section on 'Preparation for an invasive procedure'.)

•Immune thrombocytopenia (ITP) – For some elective procedures in patients with ITP, properly-timed glucocorticoids and/or intravenous immune globulin (IVIG) can be used to raise the platelet count before surgery. The table shows the expected time to first response for various ITP treatments (table 2). If time is not an issue, we generally use the agent that has previously been effective for the individual patient. (See "Initial treatment of immune thrombocytopenia (ITP) in adults", section on 'Surgery or delivery'.)

Data are limited for the use of other approaches such as administration of a thrombopoietin receptor agonist (TPO-RA) prior to surgery in individuals with ITP [57]. Indications and the time to expected response are discussed separately. (See "Clinical applications of thrombopoietic growth factors", section on 'Use of TPO receptor agonists' and "Second-line and subsequent therapies for immune thrombocytopenia (ITP) in adults", section on 'TPO receptor agonists'.)

•Liver disease – In contrast with ITP, there is evidence that individuals with liver disease who have significant thrombocytopenia and are undergoing an elective procedure with a high bleeding risk can be treated with a properly-timed TPO-RA prior to the procedure. Details are available in a separate topic. (See "Hemostatic abnormalities in patients with liver disease", section on 'Invasive procedures'.)

●Platelet dysfunction – The functional status of platelets is also important in decisions regarding platelet transfusion before or during surgery. (See "Intraoperative transfusion and administration of clotting factors" and "Intraoperative transfusion and administration of clotting factors", section on 'Platelets'.)

Some studies suggest that platelet function tests better predict surgical bleeding than the platelet count [58,59]. However, there is insufficient evidence to incorporate these tests as part of routine preoperative assessment.

Topics addressing further management of patients with specific disorders of platelet function include:

•Uremia – Many, but not all uremic patients have an increased risk of bleeding; some have an increased risk of thrombosis. (See "Uremic platelet dysfunction", section on 'Treatment of bleeding'.)

•Liver disease – Patients with severe liver disease may have platelet dysfunction in addition to thrombocytopenia. Thrombosis risk may also be increased. (See "Hemostatic abnormalities in patients with liver disease", section on 'Invasive procedures'.)

•Inherited disorders of platelet function – (See "Inherited platelet function disorders (IPFDs)".)

Management of medications affecting hemostasis — Some patients undergoing surgery are taking medications intended to reduce the risk of thrombosis (eg, warfarin or another anticoagulant, aspirin or a P2Y₁₂ inhibitor such as clopidogrel). In some cases, medications taken for other indications may alter hemostasis (eg, nonsteroidal antiinflammatory drugs [NSAIDs], herbal medications).

Appropriate perioperative management of a patient taking a specific medication depends on the indication for which the agent was prescribed, the underlying thrombotic risk, the planned surgical procedure, and other factors that affect bleeding risk [1]. Discontinuation of antithrombotic medications is often appropriate, with the details of timing typically determined using institutional or other guidelines as well as consultation with the surgeon and the prescribing clinician. These management decisions are discussed in separate topics:

●Antiplatelet agents (aspirin, other antiplatelet agents, nonsteroidal antiinflammatory agents) – (See "Perioperative medication management", section on 'Medications affecting hemostasis'.)

●Anticoagulants – (See "Perioperative management of patients receiving anticoagulants".)

●Herbal medications that affect hemostasis (eg, ginkgo biloba, garlic) – (See "Perioperative medication management", section on 'Herbal medications'.)

Management of specific hemostatic disorders — Perioperative management of patients with inherited or acquired disorders that affect hemostasis is discussed in UpToDate topics for the specific disease. The most common examples include:

●Liver disease – Patients with liver disease may have abnormalities in routine laboratory tests of coagulation, especially when liver synthetic function is significantly impaired and portal pressures are increased. These include prolongation of the PT, INR, and aPTT, as well as mild thrombocytopenia and elevated D-dimer. Both quantitative and qualitative platelet disorders are a consequence of chronic and acute liver damage. Individuals with hepatic insufficiency also have abnormalities that may increase the risk of thrombosis. Consequently, laboratory abnormalities are poor predictors of bleeding risk. (See "Hemostatic abnormalities in patients with liver disease", section on 'Laboratory abnormalities'.)

Perioperative management of hemostatic abnormalities in patients with liver disease is discussed separately. (See "Hemostatic abnormalities in patients with liver disease", section on 'Invasive procedures'.)

●Other acquired disorders of hemostasis

•Vitamin K deficiency – Vitamin K deficiency may develop in individuals with reduced oral intake or decreased absorption due to conditions such as cystic fibrosis, biliary atresia, sclerosing cholangitis, cholestasis, or intestinal diseases with malabsorption. Significant vitamin K deficiency will prolong the PT. Vitamin K deficiency can be treated with vitamin K, which may take one or more days to be effective, or with an unactivated prothrombin complex concentrate (PCC) if needed for emergency surgery with a significant bleeding risk. (See "Overview of vitamin K", section on 'Vitamin K deficiency'.)

•Disseminated intravascular coagulation – (See "Evaluation and management of disseminated intravascular coagulation (DIC) in adults", section on 'Treatment'.)

•Acquired coagulation factor inhibitors (autoantibodies against factors II, V, VII, VIII [acquired hemophilia A], IX, XI, or XIII) – (See "Acquired hemophilia A (and other acquired coagulation factor inhibitors)".)

●Inherited conditions affecting hemostasis

•Hemophilia – (See "Treatment of bleeding and perioperative management in hemophilia A and B", section on 'Elective surgery' and "Treatment of bleeding and perioperative management in hemophilia A and B", section on 'Urgent/emergency surgery'.)

•Other heritable coagulation factor deficiencies (eg, factor XIII, XI, X, VII, V, II [prothrombin], fibrinogen) – (See "Rare inherited coagulation disorders", section on 'Invasive procedure/surgery' and "Disorders of fibrinogen", section on 'Management'.)

•Von Willebrand disease (VWD) – (See "von Willebrand disease (VWD): Treatment of minor bleeding, use of DDAVP, and routine preventive care", section on 'Minor bleeding and minor surgery' and "von Willebrand disease (VWD): Treatment of major bleeding and major surgery", section on 'Overview of approach'.)

•Other disorders that cause platelet dysfunction or thrombocytopenia – (See "Inherited platelet function disorders (IPFDs)", section on 'Treatment' and "Diagnostic approach to thrombocytopenia in adults", section on 'Categories of causes'.)

Consents and advanced directives — Patient preferences and acceptance or declining various blood components and/or blood conservation modalities should be discussed in the preoperative period. Related consents and advanced directives should be obtained and documented in the preoperative period to ensure that acceptable options for optimal care are provided [1,60-62].

Certain patients may decline transfusions, or appropriate blood products may be limited or unavailable for other reasons (eg, previously transfused patients with multiple alloantibodies or incompatible cross-matching for other reasons, wounded soldiers on the battlefield, surgical procedure performed in areas of limited blood supply). These situations pose additional challenges for treatment of severe anemia, and for cases in which significant blood loss is likely [61-63]. Specific arrangements regarding acceptable alternatives should be made in advance to allow provision of the most effective care while respecting the patient's preferences, values, and their right of self-determination [61-64]. (See "Approach to the patient who declines blood transfusion", section on 'Be clear about the patient's wishes regarding consent'.)

There may be substantial variability in acceptance of various components and factors, necessitating discussion of specific transfusion decisions on an individual basis before invasive interventions [61,62,65,66]. As an example, acute normovolemic hemodilution (ANH) may be a good option for Jehovah Witnesses who consent to ANH if the blood is maintained in a contiguous circuit with the circulation. (See 'Acute normovolemic hemodilution' below.)

Investigational hemoglobin-based oxygen carriers or other oxygen delivery vehicles (eg, perfluorocarbon) have been employed in rare cases when blood components were not an option [67]. Strategies to optimize preoperative red cell mass and minimize blood loss in patients who decline blood transfusions are presented separately. (See "Approach to the patient who declines blood transfusion" and "Oxygen carriers as alternatives to red blood cell transfusion".)

Urgent and emergency surgical procedures — For urgent or emergency surgery, it may be impossible to address all factors adversely affecting baseline hemoglobin, coagulation, bleeding, and the potential need for transfusion of blood products [1]. For example, it is not possible to correct iron deficiency anemia before emergency surgery [68], because iron must be incorporated into developing blood cells. Specific issues may include the following:

●Hemorrhage – When blood loss is rapid or extensive, or when the hemoglobin level drops below a defined threshold, RBC transfusion may be necessary in the preoperative period. Perioperative indications for transfusion of RBCs are discussed in detail separately. (See "Intraoperative transfusion and administration of clotting factors", section on 'Red blood cells' and "Indications and hemoglobin thresholds for RBC transfusion in adults", section on 'Thresholds for specific patient populations'.)

In patients with major bleeding and coagulopathy (eg, due to trauma), goal-directed replacement of blood components and coagulation factors is recommended [69,70]. For those requiring massive transfusion of blood components (RBCs, plasma products, platelets), administration of crystalloid solutions should be monitored and minimized as much as possible throughout the perioperative period to avoid dilutional coagulopathy [71,72]. (See "Anesthesia for adult trauma patients", section on 'Blood and fluid administration' and "Etiology and diagnosis of coagulopathy in trauma patients" and "Ongoing assessment, monitoring, and resuscitation of the severely injured patient", section on 'VHA-based dosing'.)

●Anticoagulants – Anticoagulant reversal may be necessary before an emergency procedure [73,74]. However, not all individuals and surgical settings require reversal, especially if thrombotic risk from an underlying condition is high and bleeding risk of the surgery is low. (See "Perioperative management of patients receiving anticoagulants".)

Strategies for anticoagulant reversal for an urgent or emergency procedure are discussed in detail in separate topic reviews:

•Warfarin or other vitamin K antagonist (table 3 and table 4) – (See "Perioperative management of patients receiving anticoagulants" and "Management of warfarin-associated bleeding or supratherapeutic INR".)

A 4-component PCC product is the preferred therapy for a patient receiving a vitamin K antagonist who requires immediate reversal of anticoagulation for urgent surgery, including in the setting of intracranial hemorrhage [75]. Compared with plasma in this setting, PCC has been associated with a more rapid correction of the INR and reversal of anticoagulation [75]. Concomitant vitamin K also needs to be administered because the half-life of PCCs is short.

Details and supporting data are available in separate topics:

-Intracerebral hemorrhage – (See "Reversal of anticoagulation in intracranial hemorrhage".)

-Prosthetic heart valve – (See "Anticoagulation for prosthetic heart valves: Management of bleeding and invasive procedures".)

-All other patients – (See "Management of warfarin-associated bleeding or supratherapeutic INR", section on 'Treatment of bleeding'.)

•Direct oral anticoagulants (DOACs; direct oral thrombin inhibitor dabigatran and direct factor Xa inhibitors) (table 5 and table 6) – (See "Perioperative management of patients receiving anticoagulants" and "Management of bleeding in patients receiving direct oral anticoagulants".)

•Heparin – (See "Heparin and LMW heparin: Dosing and adverse effects", section on 'Reversal'.)

•Fondaparinux – (See "Fondaparinux: Dosing and adverse effects", section on 'Management and prevention of bleeding'.)

●Thrombocytopenia – Platelet transfusions may be required for severe thrombocytopenia in patients who require emergency major surgery when there is insufficient time to raise the platelet count by treating the underlying condition responsible for thrombocytopenia (eg, use of IVIG in an individual with ITP).

In such cases, indication for platelet transfusion includes a count that is <50,000/microL, although a higher transfusion threshold may be used in selected cases (eg, <100,000/microL for neurosurgical or ocular procedures). Platelet transfusion is usually not necessary for minor invasive procedures such as placement of a central venous catheter unless the platelet count is <20,000/microL [76-78]. (See "Platelet transfusion: Indications, ordering, and associated risks", section on 'Preparation for an invasive procedure'.)

Perioperative management of patients receiving antiplatelet therapy is discussed separately [79]. (See "Perioperative medication management", section on 'Medications affecting hemostasis'.)

INTRAOPERATIVE STRATEGIES

Transfusion thresholds — For most patients who do not have significant intraoperative blood loss (blood loss <500 mL), we use a restrictive transfusion threshold (typically defined as transfusion restricted to those with hemoglobin <7 g/dL, or in some cases, <8 g/dL) [1]. Details are discussed separately. (See "Intraoperative transfusion and administration of clotting factors", section on 'Red blood cells' and "Indications and hemoglobin thresholds for RBC transfusion in adults".)

To replace lost blood volume, transfusions should only be used if the hemoglobin threshold is reached and/or the patient exhibits clinical signs of acute anemia. However, significant bleeding (>500 mL) or bleeding at a rate such that the hemoglobin level does not accurately reflect the patient's clinical status and cannot be immediately stopped may require transfusions of red blood cells (RBCs) in addition to fluid therapy. (See "Intraoperative fluid management", section on 'Choosing fluid: Crystalloid, colloid, or blood'.)

Fluid management — Until the hemoglobin drops below the transfusion threshold (see 'Transfusion thresholds' above), we typically administer fluid as necessary to maintain normovolemia, using either a balanced electrolyte crystalloid solution administered on a 1.5:1 basis, or a colloid solution administered on a 1:1 basis with an equal volume of colloid to volume of lost blood.

Administration of standardized large volumes of crystalloid solution (eg, a fixed volume or traditional liberal approach to fluid therapy) should be avoided since this is associated with dilutional anemia and coagulopathy, which may lead to transfusions and tissue edema-related adverse outcomes. (See "Intraoperative fluid management", section on 'Avoid traditional liberal or fixed-volume approaches'.)

Acute normovolemic hemodilution — ANH is a blood conservation technique appropriate for selected patients with normal initial hemoglobin levels who are expected to lose two or more units of blood (typically ≥1000 mL) during surgery. The technique involves removal of blood from a patient shortly after induction of anesthesia, with maintenance of normovolemia using crystalloid and/or colloid replacement fluid. Details regarding technical considerations are addressed separately. (See "Surgical blood conservation: Acute normovolemic hemodilution".)

The ANH technique is safe and generally used in healthy, young adults but can be used in other populations, especially those needing extracorporeal circulation. ANH with the blood maintained in a contiguous circuit with the circulation may also be a good option if blood transfusions are not an option; however, the patient's wishes must be determined prior to the procedure [80]. (See 'Consents and advanced directives' above and "Surgical blood conservation: Acute normovolemic hemodilution", section on 'Patient selection'.)

Maintenance of normothermia — Hypothermia is avoided throughout the perioperative period in noncardiac surgical patients. Hypothermia causes coagulopathy due to impairment of platelet aggregation and reduced activity of enzymes in the coagulation cascade [81-83]. This combination of platelet and enzyme impairment typically reduces clot formation and increases perioperative blood loss and the need for transfusion [83-85]. In one meta-analysis, even mild (eg, 1°C) hypothermia increased blood loss by approximately 20 percent (figure 1) [83].

A blood warmer should be used for transfusion of all thawed or refrigerator-temperature blood products (eg, red blood cell [RBC] units, plasma products, cryoprecipitate) to avoid hypothermia <36°C, which can lead to coagulopathy, bleeding, and additional transfusions [81,86-88]. If necessary, other fluid and patient warming devices are routinely employed to maintain perioperative normothermia [89-92]. These may include warming all intravenous fluids with a commercially available blood warming device and application of upper- and lower-body forced-air warming devices and blankets. Prevention of perioperative hypothermia is discussed further in other topics:

●(See "Perioperative temperature management", section on 'Intraoperative hypothermia'.)

●(See "Achieving hemostasis after cardiac surgery with cardiopulmonary bypass", section on 'Maintenance of normothermia'.)

●(See "Massive blood transfusion", section on 'Hypothermia'.)

●(See "Etiology and diagnosis of coagulopathy in trauma patients", section on 'Hypothermia'.)

Surgical blood conservation techniques

Minimally invasive surgical techniques — Minimally invasive surgical techniques have been developed; these may decrease blood loss and need for transfusion compared with conventional open surgical procedures [4].

Electrosurgery devices — Adequate hemostasis during surgical dissection can be achieved by employing electrocautery to control bleeding from small vessels in most cases, as well as standard suturing techniques for larger vessels. These techniques are discussed separately. (See "Overview of electrosurgery", section on 'Cutting and coagulation currents'.)

Intraoperative blood salvage — Unlike preoperative autologous donation (PAD) and acute normovolemic hemodilution (ANH), in which patient's blood is collected prior to occurrence of surgical blood loss, intraoperative blood salvage (also known as blood recovery) focuses on retrieving and salvaging blood that has already been shed and is otherwise lost. The collected blood is washed or filtered and returned back to the patient as transfusion is needed. (See "Surgical blood conservation: Intraoperative blood salvage".)

Blood salvage is generally safe and associated with a very low incidence of adverse events [93]. The technique can be used during surgery to retrieve intraoperative blood loss. Benefits are most significant in procedures with high blood losses (≥1000 mL) [94,95].

In cardiac surgery, reinfusion of mediastinal blood after washing may be considered as part of a multimodal blood conservation strategy, particularly for patients who will not accept allogeneic blood products [96,97].

Details regarding patient selection, specific indications, technical considerations, advantages, and potential complications of intraoperative blood salvage are discussed separately. (See "Surgical blood conservation: Intraoperative blood salvage" and "Techniques to reduce blood loss during abdominal or laparoscopic myomectomy", section on 'Intraoperative blood salvage'.)

Topical hemostatic agents and tissue adhesives — In selected cases, topical hemostatic agents, tissue adhesives, fibrin sealants, and autologous platelet gels are used as adjuncts to standard techniques and electrocautery to control bleeding. Topical application of agents that enhance coagulation allows dosing at the application site without systemic exposure. The mechanism of action, indications, and clinical applications of these adjuncts are reviewed separately. (See "Overview of topical hemostatic agents and tissue adhesives".)

Systemic hemostatic agents — Hemostatic agents may be used to reduce the risk of bleeding or to treat excessive bleeding due to an anticoagulant or other cause of impaired hemostasis.

Antifibrinolytic agents — The most commonly used intraoperative hemostatic agents are antifibrinolytic agents (eg, tranexamic acid [TXA] and epsilon-aminocaproic acid [EACA]). Efficacy in inhibiting fibrinolysis, potential adverse effects, and perioperative use of these agents for cardiac surgery with cardiopulmonary bypass (CPB) are discussed in a separate topic. (See "Intraoperative use of antifibrinolytic agents".)

Prophylactic use of antifibrinolytics (primarily TXA) is also common during other major elective surgical procedures:

●Major orthopedic surgery (eg, total knee, hip, or shoulder arthroplasty, spine surgery) – (See "Anesthesia for total knee arthroplasty", section on 'Antifibrinolytics' and "Total hip arthroplasty", section on 'Minimizing blood loss' and "Anesthesia for elective spine surgery in adults", section on 'Antifibrinolytics'.)

●Liver transplantation or resection – (See "Liver transplantation: Anesthetic management", section on 'Administration of antifibrinolytic agents'.)

●Major gynecologic surgery – (See "Overview of preoperative evaluation and preparation for gynecologic surgery", section on 'Prophylactic tranexamic acid'.)

Administration of TXA during nonelective surgery for trauma is discussed separately:

●Acute traumatic brain injury – (See "Anesthesia for patients with acute traumatic brain injury", section on 'Tranexamic acid'.)

●Other trauma surgery

•(See "Etiology and diagnosis of coagulopathy in trauma patients" and "Ongoing assessment, monitoring, and resuscitation of the severely injured patient", section on 'Management of acute traumatic coagulopathy'.)

•(See "Initial management of moderate to severe hemorrhage in the adult trauma patient", section on 'Antifibrinolytic agents'.)

Use of TXA to treat peripartum hemorrhage is also discussed separately. (See "Postpartum hemorrhage: Medical and minimally invasive management", section on 'Administer tranexamic acid'.)

Desmopressin — Desmopressin (DDAVP) increases plasma levels of von Willebrand factor, factor VIII, and tissue-type plasminogen activator (tPA) by causing these factors to be released from platelets and endothelial cells.

●Indications and uses – In consultation with a hematologist, DDAVP is administered prophylactically for minor surgery or treatment of mild bleeding in selected patients with von Willebrand disease (VWD) or mild hemophilia A for whom a positive response to the drug has been demonstrated previously [98] (table 7). (See "Treatment of bleeding and perioperative management in hemophilia A and B", section on 'DDAVP for mild hemophilia A' and "von Willebrand disease (VWD): Treatment of minor bleeding, use of DDAVP, and routine preventive care", section on 'DDAVP'.)

DDAVP has also been administered to treat clinically significant intraoperative microvascular bleeding in patients with acquired platelet defects due to uremia or acquired von Willebrand syndrome (eg, due to chronic aortic stenosis or presence of a left ventricular assist device) [51,99]. (See "Acquired von Willebrand syndrome", section on 'Treatment of acute bleeding' and "Uremic platelet dysfunction", section on 'Acute life-threatening bleeding'.)

DDAVP may be beneficial in certain other perioperative settings (eg, intractable microvascular bleeding due to hypothermia, acidosis, aspirin use, CPB), but only small reductions in transfused RBC volume have been demonstrated [38,100,101]. Generalized perioperative use is not warranted [19,38,51]. (See "Etiology and diagnosis of coagulopathy in trauma patients" and "Achieving hemostasis after cardiac surgery with cardiopulmonary bypass", section on 'Desmopressin' and "Ongoing assessment, monitoring, and resuscitation of the severely injured patient", section on 'Other agents'.)

●Dosing – The DDAVP dose is 0.3 mcg/kg, administered intravenously by slow infusion over 30 minutes to minimize hypertension, hypotension, and flushing (table 7). Tachyphylaxis typically develops after the second dose.

●Risks – DDAVP can cause hypertension, hypotension, flushing, fluid overload, hyponatremia (which may cause seizures if close attention to free water restriction is not used), and rare thrombotic events (table 7). Monitoring of serum sodium is prudent in patients receiving more than one or two doses.

Clotting factors — Perioperative use of clotting factors including fibrinogen concentrate, prothrombin complex concentrates (PCCs), or recombinant activated factor VII (rFVIIa) is discussed in a separate topic. (See "Intraoperative transfusion and administration of clotting factors".)

POSTOPERATIVE STRATEGIES — Restrictive transfusion thresholds and individualized goal-directed treatment of coagulopathy with bleeding remain important in the postoperative period [4,102].

Close monitoring for bleeding — Postoperative bleeding is associated with mortality risk and increased health care costs [103]. During the first few hours following major surgical procedures, patients should be closely monitored to detect signs of persistent bleeding of unacceptable quantity and tempo [4].

Medical causes of bleeding should be investigated and treated.

Return to the operating room for surgical re-exploration and intervention may be necessary based on the amount, tempo, presumed location of bleeding, and potential for a surgical/anatomic cause [104].

Minimize phlebotomy — Excessive diagnostic blood draws should be avoided since this can contribute significantly to blood loss and development of hospital-acquired anemia [4,37,105-108]. Perioperative blood sampling for laboratory tests should be minimized (eg, by using smaller collection tubes when feasible). Standing orders for laboratory tests are generally avoided; rather, tests are ordered if indicated. (See "Approach to the patient who declines blood transfusion", section on 'Minimize blood loss'.)

Management of postoperative anemia — Postoperative anemia is common due to exacerbation of preoperative anemia, blood loss during surgery, and excessive postoperative phlebotomies [31,104,106-108].

Anemia may be further aggravated by reduced erythropoietin (EPO) production due to inflammatory mediators, blunted bone marrow response to EPO, and decreased iron availability, similar to patients with critical illness [104,109,110]. Anemia may significantly impact postoperative recovery and is associated with increased risk of mortality and morbidity, delayed hospital discharge, and increased costs [107].

●Diagnosis and treatment – When anemia is noted in the postoperative period, a diagnostic workup is performed to determine its cause, as illustrated in the algorithm (algorithm 2), incorporating information from the workup done in the preoperative period (eg, iron studies) [104,111]. As with preoperative anemia, postoperative anemia should not be overlooked or neglected [4,39,104]. Treatment strategies include:

•Treat iron deficiency – Since postoperative anemia is usually due to surgical blood loss, iron studies are usually appropriate, especially if anemia and/or microcytosis persist for more than one to two weeks. Treatment of postoperative iron deficiency may involve administration of intravenous iron in patients who cannot take oral medications [39,112-116]. (See "Causes and diagnosis of iron deficiency and iron deficiency anemia in adults" and "Treatment of iron deficiency anemia in adults".)

•Red blood cell transfusion – Transfusion may be necessary if postoperative hemoglobin is below a threshold (<7 to 8 g/dL in most populations) and/or if there is severe ongoing bleeding with expected severe anemia, or if there are signs of hemodynamic instability or tissue hypoxia thought to be due to severe anemia. (See "Indications and hemoglobin thresholds for RBC transfusion in adults", section on 'Thresholds for specific patient populations'.)

●Monitor resolution – All patients with postoperative anemia should have planned follow-up to determine if anemia has resolved or persists (algorithm 2).

ANEMIA CLINICAL VIGNETTES — The following hypothetical clinical case examples illustrate the principles discussed in this topic:

●Emergency surgery requiring transfusion – A 40-year-old woman presents to the emergency department following a motor vehicle crash and requires emergency splenectomy. As she arrives in the operating room, report comes from the emergency department that her complete blood count (CBC) is abnormal with mild pancytopenia (white blood count 3000/microL; hemoglobin 8 g/dL; platelet count 70,000/microL). Surgery is performed, with point of care testing revealing a decrease in hemoglobin to 6 g/dL; hemostasis is maintained. She receives a total of two units of red blood cells intraoperatively, administered in one unit increments with hemoglobin determination after the first unit showing a hemoglobin of 6.2 g/dL. Postoperatively she is evaluated by the consulting hematologist to evaluate the cause of pancytopenia.

This case illustrates a setting in which the need for emergency surgery does not allow sufficient time to perform a full evaluation of the cause of anemia; clinical judgment determines that transfusion of one unit at a time may be required in the short term; and specialist evaluation is required prior to discharge from the hospital.

●Correction of iron deficiency prior to elective surgery – A 52-year-old man with no underlying medical conditions except for chronic knee pain due to a prior sports injury is seen two weeks preoperatively for knee replacement surgery. His report of recent fatigue and mild dyspnea on exertion prompts testing of his hemoglobin level, which is found to be low at 10 g/dL. Review of his CBC reveals microcytosis (mean corpuscular volume [MCV], 79 fL), and iron studies reveal iron deficiency with a ferritin level of 10 ng/mL, consistent with iron deficiency anemia. He is treated with iron and undergoes colonoscopy, which identifies a large bleeding polyp that is removed. Iron replacement is continued. Four weeks later, his hemoglobin has risen to 14 g/dL with resolution of his fatigue and dyspnea.

After treatment of iron deficiency anemia, he undergoes knee replacement, with antifibrinolytic therapy administered during the procedure. Blood loss is approximately 500 mL, and his postoperative hemoglobin level is 12 g/dL. Transfusion is unnecessary and thus avoided. With the help of a new primary care doctor, he continues iron to completely replete iron stores, and he undergoes regular screening colonoscopy. (See "Causes and diagnosis of iron deficiency and iron deficiency anemia in adults" and "Treatment of iron deficiency anemia in adults".)

This case illustrates the importance of treating correctable causes of anemia in the preoperative period to minimize the likelihood of transfusion, the use of intraoperative antifibrinolytic therapy, and the need for postoperative follow-up. Surgical blood loss may have been further reduced by implementing blood cell salvage techniques.

●Chronic inflammatory conditions causing anemia – A 65-year-old woman with type 2 diabetes mellitus has been highly adherent with therapy and eats a well-balanced diet but continues to have mild anemia due to her underlying diabetes and high body mass index (ie, anemia of chronic disease/anemia of inflammation). Her primary clinician has performed iron studies and testing for vitamin B12 deficiency and found her levels to be adequate. She has decided to pursue laparoscopic bariatric surgery and is seen two weeks preoperatively. The preoperative evaluation includes review of her CBC obtained one week earlier by her primary clinician, who documents a mild anemia with a hemoglobin of 11.5 g/dL with normal red blood cell indices. Discussion regarding possible postponement of surgery among the patient, primary care clinician, surgeon, and anesthesiologist, resulted in a decision to proceed as scheduled in order to help treat the underlying conditions that may be contributing to her anemia. Appropriate intraoperative strategies are used to avoid exacerbation of anemia (eg, fluid and temperature management, fastidious hemostasis during surgical dissection). No transfusions are administered.

This case illustrates the need for individual evaluation of patients with chronic conditions that result in anemia, in order to exercise good clinical judgment regarding decisions to proceed with a specific surgical procedure.

The underlying cause of the anemia was addressed in each of these cases. What differs was the decision regarding whether to proceed with surgery as planned or to delay surgery to allow treatment of anemia.

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: Transfusion and patient blood management".)

SUMMARY AND RECOMMENDATIONS

●Patient blood management – Patient blood management (PBM) is a patient-centered, systematic, evidence-based approach to improve patient outcomes by managing and preserving a patient’s own blood, while promoting patient safety (table 1). (See 'Goals of patient blood management' above.)

●Preoperative strategies – The preanesthetic consultation addresses risks for bleeding and possible interventions to minimize transfusions. The history focuses on comorbidities and bleeding history. A baseline hemoglobin is obtained for patients undergoing major surgery with expected significant blood loss (>10 percent chance of requiring transfusion or >500 mL blood loss), those >65 years old (except for minor procedures), or if preoperative anemia is suspected (algorithm 1). Additional laboratory testing for patients with a possible bleeding disorder includes prothrombin time (PT) with international normalized ratio (INR), activated partial thromboplastin time (aPTT), and platelet count. (See 'Preoperative strategies' above.)

•Anemia – Depending on the cause, severity, urgency of the procedure, and anticipated blood loss, surgery is postponed when feasible to provide appropriate treatment (algorithm 1). (See 'Treatment of anemia' above.)

-Iron – Iron deficiency (with or without anemia) should be treated with iron, typically two to four weeks before surgery. Intravenous (IV) iron is an option if more urgent correction is needed or if oral iron is not well tolerated or ineffective. (See 'Iron deficiency anemia' above.)

-Erythropoietin – Decisions to administer erythropoietin (EPO) are individualized. For anemia of chronic disease/anemia of inflammation, we typically administer preoperative EPO (with supplemental iron to avoid functional iron deficiency) if hemoglobin is <12 g/dL before scheduled noncardiac surgery with expected blood loss >500 mL, or if hemoglobin <13 g/dL before cardiac surgery. (See 'Use of erythropoietin' above.)

-Transfusions – For urgent or emergency surgery, it may not be possible to treat all conditions contributing to anemia; transfusions may be needed in some cases. (See 'Urgent and emergency surgical procedures' above.)

•Thrombocytopenia or platelet dysfunction – Safe platelet counts for most surgeries are >50,000/microL (>100,000/microL for neurosurgery or ocular surgery). For immune thrombocytopenia (ITP), the platelet count may be raised using glucocorticoids or intravenous immune globulin (IVIG) if below a safe threshold. For other causes of thrombocytopenia or if there is insufficient time to treat the underlying cause, platelet transfusions may be needed. (See 'Management of thrombocytopenia or platelet dysfunction' above and "Platelet transfusion: Indications, ordering, and associated risks".)

•Antithrombotic medications – Preoperative discussions with the surgeon and primary clinician determine management based on bleeding risk for the procedure versus thrombosis risk if anticoagulants are discontinued or reversed. (See 'Management of specific hemostatic disorders' above and 'Management of medications affecting hemostasis' above and "Perioperative management of patients receiving anticoagulants".)

•Advance directives – Patient preferences and acceptance of transfusions and/or blood conservation modalities should be discussed and documented. (See 'Consents and advanced directives' above.)

●Intraoperative strategies – Restrictive transfusion thresholds should be used in stable patients. Intraoperative strategies include avoiding large volumes of crystalloid solution, avoiding hypothermia, and using electrosurgery or topical hemostatic agents when appropriate. Blood conservation techniques such as intraoperative blood salvage or acute normovolemic hemodilution (ANH) may be appropriate in selected cases. (See 'Fluid management' above and 'Maintenance of normothermia' above and 'Surgical blood conservation techniques' above.)

Antifibrinolytic agents are routinely used in cardiac surgery with cardiopulmonary bypass (CPB) and selected noncardiac surgical procedures associated with significant blood loss. (See 'Antifibrinolytic agents' above.)

Intraoperative transfusion and administration of clotting factor products are discussed separately. (See "Intraoperative transfusion and administration of clotting factors".)

●Postoperative strategies – Patients should be monitored for persistent bleeding. Blood sampling should be minimized. For postoperative anemia, a diagnostic workup is performed and treatment initiated as appropriate (algorithm 2). (See 'Postoperative strategies' above.)