Achieving hemostasis after cardiac surgery with cardiopulmonary bypass

INTRODUCTION — Blood and coagulation management are key components of anesthetic management for cardiac surgical procedures requiring cardiopulmonary bypass (CPB).

This topic discusses management of bleeding after weaning from CPB during a cardiac surgical procedure. Administration of protamine to reverse systemic anticoagulation after CPB is discussed separately. (See "Protamine: Administration and management of adverse reactions during cardiovascular procedures", section on 'Protamine administration after cardiopulmonary bypass'.)

Strategies employed before and during CPB to avoid or minimize blood loss and transfusion of blood components are discussed separately. (See "Blood management and anticoagulation for cardiopulmonary bypass".)

General principles for perioperative blood management and indications for intraoperative transfusion are discussed in separate topics. (See "Perioperative blood management: Strategies to minimize transfusions" and "Intraoperative transfusion and administration of clotting factors".)

REVERSAL OF ANTICOAGULATION ACTIVITY

Reversal of heparin anticoagulation — Systemic anticoagulation with heparin is reversed with protamine after weaning from cardiopulmonary bypass (CPB). Techniques for protamine administration, dosing considerations, and recognition, treatment, and prevention of adverse reactions to protamine are discussed separately. (See "Protamine: Administration and management of adverse reactions during cardiovascular procedures", section on 'Protamine administration after cardiopulmonary bypass'.)

Management of bivalirudin anticoagulation — In rare cases, anticoagulation with bivalirudin is used as an alternative to anticoagulation with heparin (eg, in patients with known severe protamine allergy or heparin-induced thrombocytopenia [HIT] when HIT antibodies are present). (See "Management of heparin-induced thrombocytopenia (HIT) during cardiac or vascular surgery".)

Bivalirudin has a half-life of approximately 45 minutes in normothermic patients with normal kidney function; thus, its anticoagulant effects typically resolve within approximately two hours of administration of the last dose. If bleeding is excessive in the postbypass period, more rapid offset of action may be achieved with combinations of therapies that reduce circulating blood levels and eliminate the agent (eg, dilution with blood component replacement, plasmapheresis with plasma exchange, hemodialysis) [1]. Of note, there is no reversal agent for bivalirudin.

ACHIEVING HEMOSTASIS AND MANAGEMENT OF BLEEDING — After weaning from cardiopulmonary bypass (CPB) and reversing anticoagulation, excessive bleeding may occur due to both surgical and nonsurgical causes [2]. Hemostasis depends primarily on surgical control of bleeding sites, achieving and maintaining normothermia, and selective administration of blood components as necessary. Significant blood loss may occur during any surgical procedure involving the heart and great vessels. The need for full systemic anticoagulation during CPB and adequacy of reversal after weaning from CPB, hemodilution due to fluid priming of the extracorporeal circuit, residual hypothermia after CPB, as well as fibrinolysis, platelet dysfunction, and coagulation factor consumption during CPB may all influence ability to achieve hemostasis [3,4].

Bleeding necessitating transfusion occurs commonly after cardiac surgery with CPB, although transfusion rates vary widely among institutions (10 to 90 percent) [5-7]. In general, patients who are transfused have worse outcomes than those without transfusions, but this is a strong association rather than cause-and-effect [8,9].

Preoperative risk factors for perioperative bleeding and blood transfusion after CPB include advanced age, decreased preoperative red blood cell (RBC) mass (eg, small body size, preoperative anemia), existing coagulopathy, and complex or redo operations [7,10-13]. (See "Perioperative blood management: Strategies to minimize transfusions", section on 'Preoperative strategies'.)

Intraoperative causes of excessive bleeding after CPB include inadequate surgical hemostasis, loss of platelets and coagulation factors due to high volume cell saver use, presence of residual heparin, and effects of CPB such as hemodilution, hypothermic coagulopathy, coagulopathy due to platelet activation (and consumption), and hyperfibrinolysis induced by the extracorporeal circuit. (See "Blood management and anticoagulation for cardiopulmonary bypass", section on 'Effects of cardiopulmonary bypass on hemostasis' and 'Reversal of heparin anticoagulation' above.)

Fastidious surgical hemostasis — The primary means to achieve hemostasis after CPB is meticulous surgical technique including systematic intraoperative checking of potential surgical sites of bleeding, apparent or hidden. In a meta-analysis of patients requiring mediastinal re-exploration for bleeding or cardiac tamponade after cardiac surgery, a surgical site of bleeding was identified in two-thirds of cases [14].

Maintenance of normothermia — Mild-to-moderate hypothermia is induced in most patients to provide neurologic and cardiac protection for many patients undergoing CPB, while deep hypothermia to temperatures as low as 16 to 18°C is employed for selected patients undergoing elective circulatory arrest. (See "Management of cardiopulmonary bypass", section on 'Management during cooling and hypothermia' and "Anesthesia for aortic surgery with hypothermia and elective circulatory arrest in adult patients", section on 'Considerations for anesthetic management'.)

Rewarming during CPB and subsequent maintenance of normothermia in the postbypass period are necessary because hypothermia is associated with coagulopathy due to impairment of platelet aggregation and reduced activity of clotting enzymes [15-17]. This combination of platelet and enzyme impairment reduces clot formation and increases perioperative blood loss and the need for blood transfusion [18-20].

Active warming techniques must be employed to achieve normothermia during the rewarming phase of CPB, then to maintain normothermia during the postbypass and postoperative periods. Details regarding warming strategies are available in other topics:

●(See "Management of cardiopulmonary bypass", section on 'Management during rewarming and weaning'.)

●(See "Perioperative temperature management", section on 'Active warming devices'.)

Use of transfusion algorithms — We use goal-directed protocols or algorithms to guide transfusion decisions based on measurement of hemoglobin or hematocrit (HCT), as well as assessment of specific abnormalities of hemostasis using standard laboratory tests (algorithm 1), and/or point-of-care (POC) tests of hemostasis [2]. This practice is consistent with guidelines from several professional societies for both cardiac and noncardiac surgical cases [6,7,10,21-24]. Use of such transfusion protocols and algorithms to guide decision-making can avoid or reduce unnecessary transfusions of blood components including RBCs, Fresh Frozen Plasma (FFP), platelets, and Cryoprecipitate (table 1) [2,6,7,22,25-36]. (See "Intraoperative transfusion and administration of clotting factors", section on 'Use of a transfusion algorithm or protocol'.)

●Hemoglobin or HCT levels – We check hemoglobin or HCT levels following weaning from CPB, then approximately every 30 minutes, or more frequently in a profusely bleeding patient.

●Standard laboratory coagulation tests – Standard laboratory tests include prothrombin time (PT) and international normalized ratio (INR), activated partial thromboplastin time (aPTT), fibrinogen level, and platelet count. Clinically significant bleeding at any time during the postbypass period should trigger repeat evaluation of standard laboratory tests (algorithm 1), and/or POC tests as noted below, to aid decision-making regarding which therapies will likely reverse coagulation abnormalities.

Although platelet transfusions are typically guided by platelet count, tests of platelet function can be performed. Detecting a residual effect of P2Y₁₂ inhibitors may be helpful in patients with mild-to-moderate microvascular bleeding. However, most platelet function tests are inaccurate after CPB due to dilutional changes and platelet activation [37]. In addition, these tests may not be useful in an actively bleeding patient since accuracy depends on a relatively normal platelet count. (See "Clinical use of coagulation tests" and "Platelet function testing".)

●POC tests of hemostatic function – We employ POC viscoelastic coagulation tests in addition to standard laboratory coagulation tests to guide transfusion therapy, similar to the recommendations in professional society guidelines for centers with these POC tests. Commonly used viscoelastic coagulation tests are thromboelastography (TEG), rotational thromboelastometry (ROTEM), or sonorheometry (table 2) [6,7,38]. Viscoelastic testing can either supplement standard laboratory tests of hemostatic function or in experienced hands, can stand alone and may be superior to standard tests and/or clinical judgment because assessments of coagulopathy are more rapid and contain much more information on the coagulation defect. Therefore, responses to interventions such as transfusion of blood components, or administration of hemostatic agents can be more immediately assessed [39]. Details and evidence supporting regarding use of transfusion algorithms guided by viscoelastic testing are available in a separate topic. (See "Intraoperative transfusion and administration of clotting factors", section on 'Point-of-care tests'.)

Transfusion of red blood cells — We generally transfuse RBCs if hemoglobin is <7 to 8 g/dL (or HCT <21 to 24 percent) [10,11], similar to professional society practice guidelines for blood conservation during cardiac surgery (algorithm 1) [6,7,10,11,40-42]. However, we may target a higher hemoglobin in a patient with poorly controlled hemorrhage or signs of worsening myocardial or other organ ischemia. (See "Indications and hemoglobin thresholds for RBC transfusion in adults", section on 'Cardiac surgery' and "Intraoperative transfusion and administration of clotting factors", section on 'Red blood cells' and "Massive blood transfusion".)

When transfusion is necessary, available recovered blood is returned first, followed by reinfusion of blood units harvested via normovolemic hemodilution, then transfusion of allogeneic RBCs [6,7]. (See "Surgical blood conservation: Intraoperative blood salvage" and "Blood management and anticoagulation for cardiopulmonary bypass", section on 'Acute normovolemic hemodilution'.)

Transfusion of other blood components

Plasma — Generally, fresh frozen plasma (FFP) or any other form of plasma product is transfused only in the presence of active bleeding and PT/INR or aPTT >1.5 normal ( (algorithm 1) [10,43]. Transfusion of plasma is also included in massive transfusion protocols, usually in a 1:1:1 ratio with transfusion of RBC units and platelets [44]. (See "Intraoperative transfusion and administration of clotting factors", section on 'Plasma' and "Massive blood transfusion", section on 'Component ratio (1:1:1)'.)

Outside of massive transfusion protocols, FFP is not appropriate in the absence of significant bleeding and laboratory evidence of coagulopathy [6,40,43].

Platelets — Transfusion of platelets is reserved for patients with platelet count <100,000/microL (algorithm 1), or platelet dysfunction (eg, due to residual anti-platelet drug effect after administration of antiplatelet medication, particularly P2Y₁₂ receptor inhibitors such as clopidogrel, prasugrel, and ticagrelor), but only if there is clinically significant and ongoing microvascular bleeding [6,7].

Thrombocytopenia is common in the immediate postbypass period due to a combination of hemodilution, platelet loss (eg, due to persistent surgical bleeding, adherence to the CPB circuit surface, or consumption as coagulation occurs), and accelerated clearance caused by thrombin-mediated platelet activation. (See "Intraoperative transfusion and administration of clotting factors", section on 'Platelets' and "Early noncardiac complications of coronary artery bypass graft surgery", section on 'Antiplatelet agents'.)

Transfusion of platelets is also included in massive transfusion protocols. (See "Massive blood transfusion", section on 'Component ratio (1:1:1)'.)

Rarely, thrombocytopenia occurs as a manifestation of acute disseminated intravascular coagulation (DIC) after CPB (see "Evaluation and management of disseminated intravascular coagulation (DIC) in adults", section on 'Acute DIC'), or due to heparin-induced thrombocytopenia (HIT). (See "Management of heparin-induced thrombocytopenia (HIT) during cardiac or vascular surgery".)

Cryoprecipitate versus fibrinogen concentrate — While administration of Cryoprecipitate or fibrinogen concentrate will not always resolve coagulopathic bleeding after CPB, we aggressively correct acquired hypofibrinogenemia if fibrinogen concentration is <150 mg/dL as a component of a multifactorial transfusion algorithm in patients with clinically significant bleeding [25].

●Indications – Congenital or acquired hypofibrinogenemia are clear indications for administering a fibrinogen product. Other indications are discussed separately.

The European Association for Cardio-Thoracic Surgery and the European Association of Cardiothoracic Anaesthesiology recommend fibrinogen administration for patients with low fibrinogen levels and persistent microvascular bleeding [41]. However, these groups do not recommend prophylactic fibrinogen administration since available data do not support beneficial effects such as reduction of postoperative bleeding or transfusion risks.

●Choice of product – If available, we prefer fibrinogen concentrate rather than Cryoprecipitate or FFP to treat hypofibrinogenemia because fibrinogen concentrate has less risk of infection and transfusion reactions compared with Cryoprecipitate or plasma [6,7,45-52]. However, the choice of product is based on which product is stocked at the institution. (See "Intraoperative transfusion and administration of clotting factors", section on 'Cryoprecipitate or fibrinogen concentrate'.)

Fibrinogen concentrate is typically selected to treat hypofibrinogenemia in continental Europe and Canada due to its lower risk of infection and transfusion reactions since it is not an allogeneic blood product. Cryoprecipitate is not typically available in these regions [52-55]. Although fibrinogen concentrate may be more expensive than Cryoprecipitate in the United States and the United Kingdom, the overall cost may be lower, as demonstrated in a cost-effectiveness analysis from Canadian health care system in cardiac surgical patients with active bleeding and acquired hypofibrinogenemia [56]. The increasing use of fibrinogen concentrates as a source of fibrinogen in surgical patients and dosing considerations are discussed in more detail separately. (See "Intraoperative transfusion and administration of clotting factors", section on 'Fibrinogen concentrate'.)

Cryoprecipitate is often used to treat hypofibrinogenemia in the United States and the United Kingdom because of its wider availability and lower cost in these regions compared with fibrinogen concentrate [45]. Dosing considerations for Cryoprecipitate are discussed separately. (See "Intraoperative transfusion and administration of clotting factors", section on 'Cryoprecipitate'.)

●Supporting evidence – Randomized trials suggest outcomes are similar with Cryoprecipitate and fibrinogen concentrates.

•The 2019 FIBRES (FIBrinogen REplenishment in Surgery) trial was a well-conducted trial that randomly assigned 735 individuals experiencing clinically significant bleeding and hypofibrinogenemia after cardiac surgery to receive fibrinogen concentrate (4 grams) or Cryoprecipitate (10 units) [55]. There was no difference in transfusion of additional blood components (red blood cells, platelets, and plasma).

•A 2014 trial randomly assigned 63 children <7 years undergoing elective cardiac surgery who had diffuse bleeding after heparin neutralization and fibrinogen <100 mg/dL to receive fibrinogen concentrate (60 mg/kg) or Cryoprecipitate (10 mL/kg) [57]. There were no significant differences in length of hospital stay, length of time in the intensive care unit, bleeding or thrombotic complications, or major adverse events. The fibrinogen group had a lower rate of postoperative transfusions that barely met statistical significance (87 versus 100 percent; p = 0.046).

•A 2013 trial randomly assigned 61 individuals undergoing aortic valve replacement surgery with cardiopulmonary bypass to receive fibrinogen concentrate (median dose, 8 grams) or placebo, along with standard transfusions for bleeding [49]. Compared with controls, the patients assigned to fibrinogen concentrate received fewer allogeneic transfusions (median, 13 versus 2; total avoidance of transfusion, 45 versus 0 percent). Adverse events were similar in both arms. This trial demonstrated that fibrinogen concentrate reduced allogeneic transfusions, but it was small and did not show a reduction in adverse events; comparison between fibrinogen concentrate and Cryoprecipitate was not performed.

However, as opposed to cryoprecipitate, fibrinogen concentrate does not contain von Willebrand factor (VWF), or factor VIII. Thus, it may not be ideal for all cardiac surgical patients with hypofibrinogenemia and coagulopathy due to acquired von Willebrand syndrome, particularly after a prolonged duration of CPB [45,52]. (See "Blood management and anticoagulation for cardiopulmonary bypass", section on 'Effects of cardiopulmonary bypass on hemostasis' and "Acquired von Willebrand syndrome".)

Furthermore, in nonbleeding patients, efficacy of prophylactic fibrinogen concentrate has not been demonstrated and is not recommended [52,53,58,59].

Clotting factors and hemostatic agents — Clotting factors may be used to treat excessive bleeding in selected patients during the postbypass period. Fibrinogen concentrate administration for hypofibrinogenemia is discussed above. (See 'Cryoprecipitate versus fibrinogen concentrate' above.)

Prothrombin complex concentrate products

●Prothrombin complex concentrates (PCCs) – A 4-factor unactivated PCC is approved for use in emergency surgery in patients chronically taking warfarin or another vitamin K antagonist. (See "Management of warfarin-associated bleeding or supratherapeutic INR", section on 'Urgent surgery/procedure' and "Plasma derivatives and recombinant DNA-produced coagulation factors", section on 'PCCs'.)

Off-label intraoperative administration of unactivated 4-factor or 3-factor PCC products has been evaluated for patients with intractable coagulopathy and diffuse bleeding after CPB (table 3), although data regarding intraoperative safety of PCC products in cardiac surgical patients are limited [6,7,46,60-70]. A 2022 randomized trial compared administration of PCC 15 International Units/kg versus FFP 10 to 15 mL/kg in 100 patients with excessive microvascular bleeding after CPB accompanied by a POC PT >16.6 seconds and INR >1.6 [66]. Overall efficacy and safety were comparable for PCC and FFP, with improved correction of PT and INR in patients receiving PCC. The numbers of total intraoperative RBC transfusions and total postoperative RBC transfusions were not statistically different between the groups. Other randomized and observational studies in cardiac surgical patients have also noted reductions in blood transfusions in patients receiving PCC compared with those receiving FFP, as discussed in a separate topic [65,69-71]. (See "Intraoperative transfusion and administration of clotting factors", section on 'Unactivated PCC'.)

Before considering administration of a PCC product in a cardiac surgical patient with intractable microvascular bleeding, other common causes of bleeding after CPB should be sought and treated (eg, surgical sources, thrombocytopenia, low levels of fibrinogen, platelet dysfunction, DIC) [67,72]. Dosing is discussed separately. (See "Intraoperative transfusion and administration of clotting factors", section on 'Unactivated PCC'.).

PCC products are generally avoided in patients with DIC or heparin-induced thrombocytopenia (HIT). Risk for thromboembolic events may be more likely with repeat or excessive dosing of both 4-factor and 3-factor PCCs, and may extend well into the postoperative period [69,73]. (See "Management of warfarin-associated bleeding or supratherapeutic INR", section on 'PCC risks'.)

●Activated PCCs – In contrast with unactivated PCCs, activated PCC (factor eight inhibitor bypassing activity [FEIBA]) contains activated factor VII (table 3) [67]. FEIBA has a greater prothrombotic risk compared with unactivated PCC products and is only rarely used [72,74]. (See "Plasma derivatives and recombinant DNA-produced coagulation factors", section on 'PCCs' and "Intraoperative transfusion and administration of clotting factors", section on 'Activated PCC'.)

Recombinant activated factor VII — Recombinant activated factor VII (rFVIIa) is licensed for prevention of surgical bleeding in patients with hemophilia who have developed an inhibitor to factor VIII or factor IX. (See "Treatment of bleeding and perioperative management in hemophilia A and B", section on 'Inhibitors'.).

In rare instances of severe intractable life-threatening coagulopathic bleeding after CPB, off-label administration of rFVIIa has been used in attempts to achieve bleeding cessation and reduce transfusion requirements [6,7,75-77]. However, high thromboembolism rates >20 percent (including myocardial infarction) with mortality >30 percent have been described in retrospective evaluations of registries for refractory bleeding cases [78,79]. (See "Recombinant factor VIIa: Administration and adverse effects", section on 'Off-label uses' and "Intraoperative transfusion and administration of clotting factors", section on 'Recombinant activated factor VII (rFVIIa)'.)

Similar to off-label use of PCCs (see 'Prothrombin complex concentrate products' above), other primary causes of coagulopathy should always be sought and treated before considering administration of rFVIIa. Failure to treat the primary coagulation defect increases the likelihood of an inadequate response to the initial dose of rFVIIa [78-80], and may encourage use of higher doses that are more likely to cause thrombosis [81,82]. (See "Recombinant factor VIIa: Administration and adverse effects", section on 'General approach to administration'.)

Although optimal dosing and timing of rFVIIa doses for this off-label use for intractable bleeding after CPB is unknown, we employ a cautious dosing strategy in the rare instances that rFVIIa is administered (eg, small incremental doses of 10 mcg/kg given approximately every 15 minutes). Note that this US Food and Drug Administration (FDA)-approved dose is far less than the 90 to 120 mcg/kg used in hemophilia. Thromboembolic complications are more likely with dose escalation, or in the presence of stagnant flow or presence of devices such as extracorporeal membrane oxygenation (ECMO) [6]. One study in cardiac surgical patients reported cessation of bleeding after administration of incremental aliquots of rFVIIa, at a median dose of 13.3 mcg/kg [75]. Regarding timing of administration, a randomized study reported smaller total doses were necessary if rFVIIa was administered earlier in the postbypass period when no more than one RBC unit had been transfused (12.2 [9.7-16.4] mcg/kg), while higher doses were necessary if five or more units had been transfused (18.0 [11.8-29.0] mcg/kg) [76].

Antifibrinolytic agents — Timing for discontinuing administration of a prophylactic antifibrinolytic agent (eg, epsilon-aminocaproic acid [EACA] or tranexamic acid [TXA]) that is usually initiated in the prebypass period varies among institutions. If active bleeding necessitating transfusion persists, we typically continue administration of the antifibrinolytic agent throughout the post bypass period and for several postoperative hours. (See "Intraoperative use of antifibrinolytic agents", section on 'Use of antifibrinolytic agents in cardiac surgery'.)

Desmopressin — Routine use of desmopressin (DDAVP) in cardiac surgical patients is not warranted [6,24,46]. In selected 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), we administer intravenous (IV) DDAVP 0.3 mcg/kg in the postbypass period, but only if persistent microvascular bleeding is evident [6,7,46,83-86]. DDAVP should be infused slowly over 15 to 30 minutes to avoid vasodilation. Tachyphylaxis occurs after the initial dose and during the initial three to five days of administration. (See "Uremic platelet dysfunction", section on 'Details of DDAVP administration' and "Acquired von Willebrand syndrome", section on 'Treatment of acute bleeding'.)

Some clinicians administer IV DDAVP to reduce blood loss in cardiac surgical patients with intractable microvascular bleeding due to platelet dysfunction suspected to be caused by hypothermia, acidosis, aspirin use, and/or the effects of CPB. Although very limited data suggest its benefit in such cases [6,87-90], studies are inconsistent [91,92]. Two 2017 meta-analyses of the efficacy of DDAVP in patients undergoing cardiac or noncardiac surgery noted only small reductions in perioperative blood loss and volume of RBC transfusions compared with placebo, with quality of evidence rated as low [89,90].

Possible adverse side effects of DDAVP include 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 4).

EARLY POSTOPERATIVE MANAGEMENT

Management of bleeding and coagulopathy — Close monitoring for bleeding continues in the postoperative period. Return to the operating room for mediastinal re-exploration and intervention may be necessary based on the rate and presumed location of bleeding, as well as the surgeon's assessment of potential for a surgical cause [93,94]. Excessive bleeding requiring mediastinal re-exploration has been associated with adverse outcomes that include mortality, need for mechanical circulatory support, stroke, acute kidney injury, sternal wound infection, prolonged mechanical ventilation, and increased costs [95,96].

Fastidious surgical hemostasis is the most important measure to prevent postoperative blood transfusions and surgical re-exploration. Timely preoperative cessation of anticoagulants and antiplatelet drugs is also helpful [97]. (See 'Fastidious surgical hemostasis' above and "Perioperative blood management: Strategies to minimize transfusions", section on 'Management of medications affecting hemostasis'.)

Similar to the intraoperative period, we use a hemoglobin threshold of <7 to 8 g/dL to initiate decisions to transfuse red blood cells (RBCs), but may target a higher hemoglobin in a patient with poorly controlled hemorrhage or signs of worsening myocardial or other organ ischemia. As an alternative, one randomized trial reported use of central venous oxygen saturation (SvO₂) measurements ≤65 percent as the trigger for RBC administration [98]. Transfusion of fewer RBC units was reported with this target, compared with use of a fixed hemoglobin target of <9 g/dL (odds ratio [OR] 0.03, 95% CI 0-0.15). (See 'Transfusion of red blood cells' above.)

We obtain viscoelastic tests and laboratory data, including coagulation tests and hemoglobin measurements, to guide transfusion decisions [26,36,41,42,69,99]. (See "Intraoperative transfusion and administration of clotting factors", section on 'General principles for transfusion decisions'.)

Management of anemia — Postoperative anemia is common due to exacerbation of preexisting anemia, blood loss during surgery, and excessive postoperative phlebotomies [43,100]. Management strategies are noted in the algorithm and discussed separately (algorithm 2). (See "Perioperative blood management: Strategies to minimize transfusions", section on 'Management of postoperative 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" and "Society guideline links: Management of cardiopulmonary bypass".)

SUMMARY AND RECOMMENDATIONS

●Reversal of heparin anticoagulation with protamine – Systemic heparin anticoagulation is reversed with protamine, as discussed in a separate topic. (See "Protamine: Administration and management of adverse reactions during cardiovascular procedures", section on 'Protamine administration after cardiopulmonary bypass'.)

●Reversal of bivalirudin anticoagulation – Bivalirudin is a rarely used alternative anticoagulant agent. Its anticoagulant effects typically resolve within two hours. If necessary, more rapid offset of action may be achieved with therapies that reduce circulating blood levels and eliminate the agent (eg, blood product replacement, hemodialysis, plasmapheresis with plasma exchange). (See 'Management of bivalirudin anticoagulation' above.)

●Management of intraoperative bleeding

•Surgical hemostasis – The primary means to achieve hemostasis is meticulous surgical technique. (See 'Fastidious surgical hemostasis' above.)

•Maintain normothermia – Active warming techniques to achieve and maintain normothermia are employed as necessary. (See 'Maintenance of normothermia' above.)

•Use a transfusion algorithm – We use a goal-directed protocol or algorithm to guide transfusion decisions, based on measurement of hemoglobin or hematocrit (HCT), assessment of specific abnormalities of hemostasis using standard laboratory tests of hemostatic function (algorithm 1), as well as point-of care viscoelastic tests of coagulation if available (eg, thromboelastography [TEG], rotational thromboelastometry [ROTEM], or sonorheometry (table 2)). (See 'Use of transfusion algorithms' above.)

Transfusion decisions for individual blood components include (table 1):

-Red blood cells (RBCs) – We typically transfuse RBCs for hemoglobin <7 to 8 g/dL (or HCT <21 to 24 percent). Available recovered blood is returned first, followed by reinfusion of blood units harvested via normovolemic hemodilution, then transfusion of allogeneic RBCs. (See "Indications and hemoglobin thresholds for RBC transfusion in adults", section on 'Cardiac surgery' and "Intraoperative transfusion and administration of clotting factors", section on 'Red blood cells' and 'Transfusion of red blood cells' above.)

-Plasma – Plasma products are transfused when prothrombin time (PT)/international normalized ratio (INR) or aPTT >1.5 times normal, but only if the patient has active and ongoing bleeding. (See 'Plasma' above.)

-Platelets – Transfusion of platelets is reserved for patients with platelet count <100,000/microL or platelet dysfunction (eg, due to residual anti-platelet drug effects) if there is clinically significant and ongoing bleeding. (See 'Platelets' above.)

-Cryoprecipitate or fibrinogen concentrate – We aggressively correct hypofibrinogenemia (fibrinogen <150mg/dL) in patients with active bleeding. (See 'Cryoprecipitate versus fibrinogen concentrate' above.)

In the United States and the United Kingdom, Cryoprecipitate is often used to treat hypofibrinogenemia because of its wider availability and lower cost.

In continental Europe and Canada, fibrinogen concentrate is preferred for treatment of hypofibrinogenemia because it has a lower risk of infection and transfusion reactions.

•Coagulation factor concentrates and hemostatic agents

-Prothrombin complex concentrate (PCC) – For patients with intractable coagulopathy and diffuse bleeding after CPB, or for those intolerant of high FFP transfusion volume, off-label intraoperative use of unactivated 4-factor or 3-factor PCC products is reasonable (table 3). However, other causes of intractable microvascular bleeding should be treated before considering a PCC product, and PCCs are avoided in patients with prothrombotic risks. (See 'Prothrombin complex concentrate products' above.)

-Recombinant activated factor VII (rFVIIa) – In rare instances of severe intractable life-threatening coagulopathic bleeding after CPB, off-label administration of rFVIIa has been used in attempts to achieve bleeding cessation and reduce transfusion requirements. (See 'Recombinant activated factor VII' above.)

-Antifibrinolytic agents – If active bleeding necessitating transfusion persists, we typically continue the antifibrinolytic agent throughout the postbypass period and into the postoperative period. (See 'Antifibrinolytic agents' above.)

-Desmopressin (DDAVP) – Intravenous (IV) DDAVP 0.3 mcg/kg is administered in selected patients with acquired platelet defects due to uremia or those with acquired von Willebrand disease (table 4), but only if persistent microvascular bleeding is evident. (See 'Desmopressin' above.)

●Postoperative management

•Management of postoperative bleeding – Close monitoring for bleeding continues in the postoperative period. Return to the operating room for surgical re-exploration is occasionally necessary based on the rate and presumed location of bleeding, as well as the surgeon’s assessment of potential for a surgical cause. (See 'Management of bleeding and coagulopathy' above.)

•Management of postoperative anemia (algorithm 2) – (See 'Management of anemia' above.)