Intraoperative transfusion and administration of clotting factors

INTRODUCTION — This topic will review general principles guiding intraoperative decisions to transfuse blood components, and the indications, risks, benefits, and alternatives for administration of specific components.

Strategies employed to avoid or minimize perioperative transfusion are discussed separately. (See "Perioperative blood management: Strategies to minimize transfusions".)

The following intraoperative circumstances are discussed separately:

●Cardiac surgery after cardiopulmonary bypass – (See "Achieving hemostasis after cardiac surgery with cardiopulmonary bypass", section on 'Transfusion of red blood cells' and "Achieving hemostasis after cardiac surgery with cardiopulmonary bypass", section on 'Transfusion of other blood components'.)

●Perioperative massive transfusion – (See "Massive blood transfusion".)

Indications for and general risks associated with transfusion of specific blood components in any setting are addressed in separate topics:

●Red blood cells (adults) (see "Indications and hemoglobin thresholds for RBC transfusion in adults")

●Red blood cells (children) (see "Red blood cell transfusion in infants and children: Indications")

●Plasma (see "Clinical use of plasma components")

●Platelets (see "Platelet transfusion: Indications, ordering, and associated risks")

●Cryoprecipitate (see "Cryoprecipitate and fibrinogen concentrate")

PREPARATIONS FOR LARGE EXPECTED BLOOD LOSSES

Elective surgery with risk for significant blood loss

●Estimate expected blood loss – For elective procedures associated with clinically significant bleeding, the patient's total blood volume and the overall amount and rate of expected blood loss are estimated in the preoperative period in consultation with the surgeon. (See 'Estimating blood loss' below.)

●Type and crossmatch – Pretransfusion testing (typing and crossmatching) for red blood cells (RBCs) is routinely performed in the preoperative period for selected procedures with known risk for significant blood loss (eg, open repair of abdominal aortic aneurysm, hepatic resection). For such cases, RBC units should be cross matched and readily available for the operating team before surgical incision. If large volume blood loss is possible, preoperative communication between the anesthesiologist and the transfusion service is necessary to ensure that additional RBC units and other blood components will be readily available during the surgical procedure, and that there are no risk factors affecting access to additional cross-matched units (eg, rare blood type or known RBC alloantibodies). (See "Pretransfusion testing for red blood cell transfusion".)

In addition to procedure-specific factors, the likelihood of transfusion is also influenced by preoperative laboratory evidence of coagulopathy and/or presence of anemia [1,2]. In a large retrospective study of 672,075 patients who had a coagulation profile obtained before common elective noncardiac and cardiac surgical procedures, abnormal findings in the preoperative international normalized ratio (INR) or platelet count were associated with risk of bleeding resulting in transfusion during both the intraoperative and postoperative periods [3]. Preoperative anemia should be addressed before any elective surgical procedure if possible (ie, the underlying cause determined and optimal treatment provided) [4]. Details are discussed separately. (See "Perioperative blood management: Strategies to minimize transfusions", section on 'Treatment of anemia'.)

●Prepare for blood conservation techniques when appropriate – In many cases, management includes planning for use of intraoperative techniques such as acute normovolemic hemodilution (ANH) or blood salvage to avoid or minimize the need for allogeneic transfusions. Indications, candidate selection, and technical aspects of these surgical blood conservation techniques are discussed separately. (See "Surgical blood conservation: Acute normovolemic hemodilution" and "Surgical blood conservation: Intraoperative blood salvage".)

Emergency surgery with possibility of massive blood transfusion — For patients with hemorrhage who require emergency surgery and possibly massive transfusion, early communication with the institutional blood bank or transfusion medicine service is necessary for activation of a massive transfusion protocol to order appropriate amounts and types of blood components. Details are discussed in a separate topic. (See "Massive blood transfusion".)

Typically, RBCs, plasma, and platelets are ordered and transfused in approximately equal (1:1:1) ratios as soon as these blood components are available (either before and/or during surgery). If RBC units have not been made available and blood is urgently needed, the transfusion service can provide "immediate release" blood without pretransfusion testing. The universal donor for immediate release RBCs is type O, RhD-negative. The universal donor for immediate release plasma is type AB, RhD-positive. (See "Pretransfusion testing for red blood cell transfusion", section on 'Emergency release blood for life-threatening anemia or bleeding'.)

Examples of surgical cases that may encounter early activation of a massive transfusion protocol include:

●Trauma surgery – (See "Massive blood transfusion", section on 'Trauma' and "Initial management of moderate to severe hemorrhage in the adult trauma patient".)

●Aortic rupture – (See "Surgical and endovascular repair of ruptured abdominal aortic aneurysm", section on 'Preparation'.)

●Obstetric hemorrhage – (See "Postpartum hemorrhage: Management approaches requiring laparotomy" and "Postpartum hemorrhage: Medical and minimally invasive management".)

TECHNICAL ASPECTS OF BLOOD TRANSFUSION

Establishing intravenous access — If significant blood loss is anticipated, adequate intravenous (IV) access is necessary for possible blood product transfusion(s). If rapid fluid and blood product administration is anticipated, large-bore catheters with short lumens should be employed for optimal flow, in addition to the use of rapid infusion systems that will allow administration of large volumes more quickly [5,6]. If patient positioning for the planned surgical procedure will create challenges for obtaining additional access, all IV catheters should be inserted prior to final positioning, with confirmation of patency and flow after final patient positioning.

Either peripheral or central routes of access may be selected:

●Peripheral venous access – Large-bore (eg, 14 or 16 gauge) peripheral IV catheters (or a short 7 French rapid infusion catheter inserted using a modified Seldinger technique) may be selected [7,8]. Peripheral catheters are typically placed in the upper extremities. Compared with a central venous catheter (CVC), peripheral catheters are generally associated with fewer complications. However, large-bore peripheral venous access is not feasible in some patients due to body habitus, vein fragility, or prior use of multiple peripheral veins. (See "Peripheral venous access in adults".)

●Central venous access – A single-lumen, large-bore central venous introducer sheath or other CVC with large lumen(s) provides reliable access for blood and fluid administration, as well as central venous access for infusion of vasoactive agents. Either a multilumen CVC or a large, single-lumen introducer sheath (typically, 8.5 French) may be used. Multilumen catheters have limited flow properties due to long length and smaller lumens, while an introducer sheath allows rapid flow through its single lumen (and may be used for later placement of a pulmonary artery catheter [PAC] if necessary) [9,10]. (See "Central venous access in adults: General principles".)

Avoiding transfusion errors — Practices to ensure that the intended blood components are given to the intended recipient are critical for preventing serious transfusion reactions. Extra caution is required to ensure that individuals caring for the patient do not bypass manual system checks that are in place to avoid errors during urgent surgical cases. Safety improvements such as barcode scanners installed in operating rooms increase adherence to protocols and may decrease likelihood of transfusion errors [11,12]. (See "Practical aspects of red blood cell transfusion in adults: Storage, processing, modifications, and infusion", section on 'Pre-transfusion considerations'.)

Use of filters — All red blood cell (RBC) units, plasma, and platelets should be transfused through a standard 170 to 260 micron filter (contained as an integral part of a standard infusion set), which is designed to remove clots and aggregates.

In the United States, most blood product units released for transfusion are leukoreduced at the time of collection. If pre-storage leukoreduction was not performed, an add-on filter for leukoreduction may be used, although these filters will likely restrict rapid flow of blood during emergency transfusion. (See "Practical aspects of red blood cell transfusion in adults: Storage, processing, modifications, and infusion", section on 'Pre-storage leukoreduction'.)

Thawing and warming components, use of blood warmers — Frozen blood components are thawed on demand. Refrigerated components such as RBCs should be kept cold until a decision has been made to transfuse each one.

●RBCs and plasma – When possible, cold and previously thawed blood components (RBC units and plasma) should be administered via a blood warmer to avoid causing systemic hypothermia with resultant coagulopathy and other adverse effects [13-20].

●Cryoprecipitate and platelets – Cryoprecipitate units are thawed to room temperature and should be administered within six hours of thawing; use of a blood warmer is unnecessary. Platelets are stored at room temperature and are typically infused via separate IV tubing that is not connected to a blood warmer. However, if the patient is hypothermic, use of a blood warmer to administer cryoprecipitate or platelets is not prohibited [21,22]. (See "Practical aspects of red blood cell transfusion in adults: Storage, processing, modifications, and infusion", section on 'Administering the transfusion'.)

Administration with compatible fluids — Only compatible fluids are coadministered with RBCs through the IV tubing (see "Practical aspects of red blood cell transfusion in adults: Storage, processing, modifications, and infusion", section on 'Compatible fluids'):

●If dilution of packed RBCs is necessary (such as during rapid intraoperative transfusion), the blood banking community recommends 0.9 percent saline (normal saline).

●Normal saline, albumin, or plasma can be administered through the same tubing as RBCs. Modern rapid infusion devices have reservoirs into which practitioners can add RBCs together with plasma in their desired combination (typically one plasma unit for each RBC unit).

●In practice, anesthesiologists often coadminister other isotonic crystalloid solutions that have sodium and other electrolyte composition similar to plasma (eg, lactated Ringer's solution, Plasmalyte, Normosol) without adverse events.

●Dextrose (5 percent in water) or hypotonic solutions (eg, 0.45 percent saline) should never be coadministered with RBCs, because RBCs will take up glucose and/or free water and lyse. Hypertonic solutions (eg, 3 percent saline) should also be avoided.

Other blood components (eg, platelets, cryoprecipitate) should be administered alone via separate tubing, or in tubing containing 0.9 percent sodium chloride. Importantly, cryoprecipitate may clot in IV tubing if that tubing still contains active thrombin from previously transfused blood components such as platelets [23,24].

Returning unused components — Unused blood components must be returned to the blood bank for possible use in another patient or appropriate disposal.

To avoid wastage, RBCs should be removed from refrigerated storage immediately before use and should never be left to warm up at room temperature for long periods. RBC units that were not transfused should be returned to the blood bank with notation regarding the duration they were out of refrigerated storage. This helps with record-keeping. The blood bank will not transfuse RBCs to another person if they were unrefrigerated for longer than 30 to 60 minutes [25]. (See "Practical aspects of red blood cell transfusion in adults: Storage, processing, modifications, and infusion", section on 'Storage/transport temperature'.)

Blood components that are not needed are never transfused to avoid wastage, because this exposes the patient to unnecessary risks.

GENERAL PRINCIPLES FOR TRANSFUSION DECISIONS

When to transfuse — Transfusions are a potentially lifesaving temporizing measure in patients who are bleeding. However, controlling the source of bleeding is more important. (See 'Use of a transfusion algorithm or protocol' below.)

Major factors influencing intraoperative decisions to transfuse red blood cells (RBCs) and other blood components include estimates of the amount of current and expected ongoing blood loss, evidence of intractable microvascular bleeding indicating coagulopathy, and clinical signs of anemia (eg, tachycardia, hypotension, dilute-appearing blood in the surgical field, pallor). The need to transfuse should be confirmed with diagnostic tests for anemia and coagulation function whenever possible.

For individuals without rapid bleeding, further administration of RBCs is avoided if the hemoglobin concentration is >7 to 8 g/dL in healthy patients (or >9 g/dL in older patients with high risk or evidence of ischemia). Supporting evidence for using this restrictive transfusion threshold and possible exceptions are discussed separately and below. (See 'Red blood cells' below and "Indications and hemoglobin thresholds for RBC transfusion in adults".)

Further administration of other blood components is avoided if active microvascular and surgical bleeding have ceased. However, individuals with active ongoing bleeding may require additional coagulation testing to guide appropriate selection of additional blood components. When bleeding is too rapid to be monitored with measurements of hemoglobin concentration, the number of transfused units is individualized based on estimated ongoing blood loss.

Estimating blood loss — There is no clear consensus regarding optimal methods for assessing blood loss. The following methods are used, but are subject to inaccuracies [26-33]:

●Subjective estimates of blood loss, typically based on periodic visual assessment of the surgical field and communication with the surgeon regarding excessive microvascular bleeding at surgical dissection or wound sites and perceived volume and persistence of blood loss.

●Estimates based on standard quantitative methods including monitoring blood suction canister volumes, the number and degree of saturation of surgical sponges and drapes, as well as serial laboratory measurements.

●Trends in hemoglobin concentration could be misleading if time for equilibration is not permitted. Estimates are based on a combination of factors including blood components transfused, clinical estimates of circulating volume, and changes in hemoglobin.

Intraoperative diagnostic testing — Estimates of blood loss may prompt testing for anemia and hemostatic function to determine if administration of RBCs or other blood components is indicated (plasma, platelets, cryoprecipitate). These decisions are based in part on results of these tests, but the specific intraoperative context is always considered. (See 'Indications and risks for specific blood components' below.)

Standard tests — Standard laboratory tests include hemoglobin concentration. In intraoperative settings, results of these tests may be available within a few minutes depending on local laboratory resources.

Standard coagulation tests (prothrombin time [PT], international normalized ratio [INR], and activated partial thromboplastin time [aPTT]), fibrinogen level, and platelet count are obtained if coagulopathy is suspected. The time required for processing and reporting standard coagulation tests, platelet count, and fibrinogen concentration is typically 45 to 90 minutes and may be longer. Thus, the utility of these standard tests for assessing cause(s) of bleeding and coagulopathy is limited in rapidly changing intraoperative situations.

Point-of-care tests — When available, rapid point-of-care (POC) tests can provide more timely information compared with standard tests, allowing more rapid decision-making regarding the need for targeted transfusion of blood components.

Hemoglobin measurements — In many institutions, rapid estimates of hemoglobin is obtained using arterial blood gas machines located in or near the operating room. We also use an automated analyzer for POC complete blood counts.

Although POC instruments to measure hemoglobin are available, these are not as accurate as standard laboratory measurements [34-39]. Accuracy can be altered by sample source (hemoglobin measurements are highest in capillary > venous > arterial blood samples), use of a tourniquet which falsely lowers hemoglobin levels, and administration of intravenous fluids which may acutely hemodilute the blood sample and decrease the hemoglobin level [38,39].

Tests of coagulation function — POC tests of coagulation function allow rapid assessment of coagulopathy and responses to blood product transfusion. We agree with professional society recommendations regarding use of viscoelastic testing (VET), if available (eg, thromboelastography [TEG] or an adaptation of TEG known as rotational thromboelastometry [ROTEM]), to test overall coagulation function during selected surgical procedures such as cardiac surgery or liver transplant [40-50]. The role of viscoelastic POC methods continues to develop in other patient populations with significant bleeding, including obstetrics and orthopedic surgery [51]. However, VETs are not available in every institution [52]. Even in institutions that do use VETs, standard laboratory coagulation tests are also recommended to provide additional information [44].

With VET, a tracing result provides information regarding clot initiation, kinetics of clot formation, clot strength, and fibrinolysis (figure 1 and figure 2 and table 1):

●Primary fibrinolysis (figure 3A-B)

●Secondary hyperfibrinolysis (figure 3A, 3C)

●Thrombocytopenia (figure 3A, 3D)

●Clotting factor consumption (figure 3A, 3E)

●Hypercoagulability (figure 3A, 3F)

In general, randomized trials and observational studies in surgical patients have noted that use of VET (with or without a transfusion algorithm) reduces RBC and possibly FFP and platelet transfusions, compared with standard care based on standard laboratory coagulation tests and/or clinical judgment, although results are inconsistent, particularly in noncardiac surgical procedures [45,50,53-89]. Evidence presented in meta-analyses has been limited by heterogeneity among studies since the TEG or ROTEM parameters used for a transfusion algorithm or protocol were institution-specific for each study, as well as high risk of bias, imprecision, and/or indirectness [53-58,77,79,80].

VET-based transfusion of blood components is also commonly used to manage the acute coagulopathy associated with trauma. Although VETs can be performed rapidly, patients requiring resuscitation using a rapid transfuser device are less likely to benefit from such testing compared with those undergoing transfusion of fewer units at a slower rate. Details are discussed in other topics:

●(See 'Use of a transfusion algorithm or protocol' below.)

●(See "Clinical use of coagulation tests", section on 'Point-of-care testing'.)

●(See "Etiology and diagnosis of coagulopathy in trauma patients", section on 'Viscoelastic hemostatic assays' and "Ongoing assessment, monitoring, and resuscitation of the severely injured patient", section on 'VHA-based dosing'.)

Also, if available, POC aggregometry may be performed to test platelet function when platelet dysfunction is suspected. Detecting a residual effect of P2Y12 inhibitors may be helpful in the setting of mild to moderate bleeding. However, testing for platelet dysfunction may not be useful in an actively bleeding patient if results are not immediately available, and the accuracy of most tests depends on a relatively normal platelet count. Also, these tests are not accurate after cardiopulmonary bypass due to dilutional changes and platelet activation [90]. (See "Etiology and diagnosis of coagulopathy in trauma patients", section on 'Platelet dysfunction' and "Clinical use of coagulation tests" and "Platelet function testing".)

Use of a transfusion algorithm or protocol — Similar to recommendations in the practice guidelines of several professional societies, we use a goal-directed protocol or algorithm to guide transfusion decisions based on measurement of hemoglobin and assessment of specific abnormalities of coagulation, either obtained from standard laboratory tests or POC viscoelastic tests VET, such as TEG (table 1 and table 2) or ROTEM [40-49,89].

Overall, use of an algorithm reduces unnecessary transfusions of RBCs, plasma, platelets, and cryoprecipitate while allowing optimal treatment of coagulopathy during major surgical procedures. However, no trials have prospectively compared different algorithms. (See 'Standard tests' above and 'Point-of-care tests' above.)

For patients with severe and ongoing or massive hemorrhage, transfusion decisions are not based exclusively on the most recent hemoglobin value and tests of hemostasis. In such patients, more aggressive transfusion may be necessary to compensate for ongoing blood loss, as discussed separately. (See "Massive blood transfusion", section on 'Approach to volume and blood replacement'.)

It is imperative to continue efforts to control the source of bleeding even as a patient is being massively transfused, as it is source control, not transfusion, that is the definitive treatment. Transfusion is only a temporizing measure until bleeding can be stopped. The ultimate manifestation of this concept is the "Stop the Bleed" campaign, in which bystanders are taught to apply a tourniquet to a limb that has sustained a life-threatening arterial injury [91].

INDICATIONS AND RISKS FOR SPECIFIC BLOOD COMPONENTS

Red blood cells

●Use of a restrictive transfusion strategy – We transfuse autologous, salvaged, or allogeneic red blood cell (RBC) units when the hemoglobin is below a specific threshold for the clinical situation. Typically, this involves hemoglobin <7 to 8 g/dL in most cardiac and noncardiac surgical patients without significant ongoing bleeding. These threshold values are similar to the guidelines of several professional societies for use of a restrictive transfusion strategy [40-42,44,46-49,92,93]. (See "Indications and hemoglobin thresholds for RBC transfusion in adults", section on 'Overview of our approach'.)

Trials in surgical patients (including older adults with comorbidities) have compared restrictive transfusion strategies (typically defined as Hgb <7 or <8 g/dL, depending on the study) versus more liberal transfusion strategies (typically defined as Hgb <9 or <10 g/dL). Most have noted decreases in the number of RBC units transfused in patients managed with a restrictive strategy, without higher incidences of mortality, myocardial infarction, stroke, kidney failure, or infection with either strategy [41,44,46-49,94-110]. Although the majority of studies show no benefit from liberal transfusions, restrictive strategy has been associated with increased risk of mortality in selected studies [111,112]. Important limitations of trials comparing restrictive versus liberal transfusion strategies include variability in post-transfusion hemoglobin targets, difficulties in precisely maintaining a selected target, differences in endpoints (eg, percentage of patients transfused versus number of units transfused per patient), and differences in the time periods studied (eg, intraoperative, postoperative, or both periods) [113]. These trials are summarized in a separate topic. (See "Indications and hemoglobin thresholds for RBC transfusion in adults", section on 'Thresholds for specific patient populations'.)

The decisions to transfuse RBC units are carefully considered and individualized. For example, if a patient is known to tolerate a hemoglobin concentration <7 g/dL, then there may not be a need for transfusion. Conversely, we typically use a hemoglobin threshold of <9 g/dL in patients with known acute coronary syndrome or signs of myocardial or other organ ischemia [94,95,111,114-120]. Myocardial ischemia may be diagnosed by changes noted on the electrocardiogram (ECG), pulmonary artery catheter (PAC), or with transesophageal echocardiography (TEE), while poor perfusion and ischemia of other organs may manifest as increased lactate levels or decreased mixed venous oxygen saturation, or urine output. Also, in cases with rapid blood loss or significant ongoing bleeding, immediate transfusion may be necessary before quantitative laboratory assessment of hemoglobin can be obtained, based on the rate of bleeding, expected volume of ongoing bleeding, and the preoperative red cell mass. However, there is general consensus that transfusion of packed RBC units is recommended if Hgb <6 g/dL, and that transfusion is rarely indicated if Hgb >10 g/dL. (See "Indications and hemoglobin thresholds for RBC transfusion in adults", section on 'Thresholds for specific patient populations'.)

We reassess hemoglobin levels after transfusion to inform decisions regarding whether additional RBC units are needed. Accurate assessment of a post-transfusion hemoglobin level can be performed as early as 15 minutes following completion of RBC administration (in the absence of ongoing active bleeding) [121,122]. However, when blood loss is rapid and significant, immediate life-saving transfusion may be necessary before quantitative laboratory assessment of hemoglobin can be obtained, based on the rate of bleeding and expected total volume of blood [41,42]. Although noninvasive hemoglobin measurements are still obtained in such situations, these will not accurately reflect the degree of reduced red cell mass [39].

●Risks of transfusion – There are inherent risks associated with either perioperative anemia and with transfusion as a therapy [123].

Adverse events can occur in individuals receiving transfusions. Some adverse events are likely related to severity of comorbidities rather than direct complications of transfusion:

•Infection and immunomodulation [124-127]

•Cardiovascular complications [123,128]

•Mortality [111,112,122-124,127,129]

•Acute kidney injury [106,107,123,130]

General risks associated with transfusion of RBCs are noted below. (See 'Risks of blood transfusion' below.)

Massive transfusion can be associated with additional risks including metabolic complications [131,132]. (See "Massive blood transfusion", section on 'Complications' and "Early noncardiac complications of coronary artery bypass graft surgery", section on 'Blood transfusion'.)

●Risks of anemia – Anemia has been associated with higher mortality in surgical patients [133-135]. In one study of patients who declined perioperative transfusion, mortality was 21 percent in those with a hemoglobin nadir of 6.1 to 7 g/dL, but increased to 41 percent in those with a lower hemoglobin nadir of 5.1 to 6 g/dL [133]. (See "Indications and hemoglobin thresholds for RBC transfusion in adults", section on 'Rationale for transfusion'.)

Platelets

●Indications – Similar to recommendations in the practice guidelines of several professional societies, we transfuse platelets to maintain adequate platelet count in surgical patients, typically >50,000/microL or >100,000/microL when central nervous system bleeding is present or likely [40-49,89,136]. Platelet transfusions are also a component of massive transfusion protocols. Most recommendations are based on expert consensus; evidence is discussed separately. (See "Platelet transfusion: Indications, ordering, and associated risks", section on 'Indications for platelet transfusion'.)

Abnormalities of platelet function affect clotting even if platelet count is adequate. Thus, if ongoing bleeding is suspected to be due to qualitative platelet defects, platelet transfusion may be used [136]. Examples include emergency surgery in patients with qualitative platelet defects caused by chronic use of antiplatelet agents that inhibit cyclooxygenase, glycoprotein IIb/IIIa, and/or adenosine diphosphate (ADP), or uremic platelet dysfunction when there is insufficient time for dialysis. (See "Uremic platelet dysfunction", section on 'Invasive procedures'.)

Platelet dysfunction due to aspirin, dipyridamole, P2Y₁₂ receptor antagonists, or reversible GP IIbIIIa antagonists (eg, eptifibatide) may not be detected by point-of-care (POC) viscoelastic testing (VET) such as thromboelastography (TEG) or rotational thromboelastometry (ROTEM) [50,137]. (See 'Tests of coagulation function' above.)

Further information regarding the utility of POC tests of coagulation for diagnosis of platelet-dependent bleeding is available in separate topics:

•(See "Platelet transfusion: Indications, ordering, and associated risks", section on 'Specific clinical scenarios'.)

•(See "Clinical use of coagulation tests", section on 'Point-of-care testing'.)

•(See "Etiology and diagnosis of coagulopathy in trauma patients", section on 'Viscoelastic hemostatic assays' and "Ongoing assessment, monitoring, and resuscitation of the severely injured patient", section on 'VHA-based dosing'.)

We typically avoid prophylactic intraoperative platelet transfusions in patients who are not bleeding, especially if the platelet count is >50,000/microL [138]. Exceptions may be made if consequences of even minor bleeding would be severe (eg, ophthalmic procedures or neurosurgery), or if a surgical procedure is likely to cause significant bleeding. (See "Platelet transfusion: Indications, ordering, and associated risks", section on 'Actively bleeding patient'.)

●Preparations – Platelets can be obtained by apheresis from a single donor or as pooled units of whole blood derived platelets (typically derived from whole blood donations from four to six different donors) (table 3). One apheresis unit is equivalent to four to six pooled platelet units. Although exact platelet quantities vary, each platelet dose (one apheresis unit or a pool of whole blood derived platelets) contains approximately 3 to 4 x 10¹¹ platelets suspended in 200 to 300 mL of plasma and will increase the platelet count by approximately 30,000/microL to 50,000/microL in a non-bleeding adult (table 3). (See "Platelet transfusion: Indications, ordering, and associated risks", section on 'Whole blood derived (WBD) versus apheresis platelets'.)

●Risks – General risks of platelet transfusion, including alloimmunization, are the same as other blood components, as noted below [139]. (See 'Risks of blood transfusion' below.)

Historically, the risk of bacterial infection is higher with platelets compared with other blood components due to storage at room temperature; this increased risk has been substantially mitigated by the addition of risk reduction methods (eg, bacterial culture and pathogen inactivation). Rarely, post-transfusion purpura may occur. (See "Transfusion-transmitted bacterial infection".)

Plasma

●Indications – The main indication for plasma, including Fresh Frozen Plasma (FFP) or plasma frozen within 24 hours of collection (PF24), is reversal of warfarin in preparation for urgent surgery when a prothrombin complex concentrate (PCC) is not available (table 4). The initial dose depends on body weight and internation normalized ratio (INR) and is adjusted using laboratory testing. (See "Perioperative management of patients receiving anticoagulants", section on 'Urgent/emergency invasive procedure' and "Management of warfarin-associated bleeding or supratherapeutic INR", section on 'Urgent surgery/procedure'.)

Similar to recommendations in the practice guidelines of several professional societies, other intraoperative uses of plasma include (table 3) [40-49]:

•As a component of massive transfusion protocols. (See "Massive blood transfusion", section on 'Approach to volume and blood replacement'.)

•In patients with ongoing clinically significant bleeding, particularly if intracranial hemorrhage is present, if there are suspected or documented severe abnormalities of clotting (eg, INR >2.0 or abnormalities of viscoelastic testing due to vitamin K deficiency) (figure 3A, 3E) [50]. (See 'Tests of coagulation function' above and 'Standard tests' above.)

However, plasma is not administered to stable nonbleeding patients solely to "correct" an elevated INR (INR up to 2) [140]. The rationale is discussed separately. (See "Clinical use of plasma components", section on 'Settings in which plasma is not appropriate'.)

•Other rare indications that may be relevant in the perioperative period are discussed separately. (See "Clinical use of plasma components", section on 'Overview of indications'.)

●Risks – Risks of FFP transfusion are noted below. (See 'Risks of blood transfusion' below.)

Cryoprecipitate or fibrinogen concentrate — As stated in the practice guidelines of several professional societies [40-49], cryoprecipitate or fibrinogen concentrate is administered to patients with clinically significant bleeding when the fibrinogen concentration is <150 mg/dL or when hypofibrinogenemia is suspected and fibrinogen cannot be measured in a timely fashion (table 3) [88,141-144]. Abnormally low concentrations of fibrinogen can result in impaired clot formation and increased bleeding.

Clinical use of cryoprecipitate has become obsolete in some parts of Europe due to the availability of fibrinogen concentrates [145-147]. In the United States and the United Kingdom, cryoprecipitate is still commonly used because of its wider availability and lower cost compared with fibrinogen concentrate. (See "Disorders of fibrinogen", section on 'Fibrinogen concentrate: Dosing and monitoring'.)

●Indications and uses – Fibrinogen concentrate or cryoprecipitate has been used to treat life-threatening intraoperative bleeding due to:

•Hypofibrinogenemia, with fibrinogen concentration <150 mg/dL [44,148]. (See "Achieving hemostasis after cardiac surgery with cardiopulmonary bypass", section on 'Cryoprecipitate versus fibrinogen concentrate' and "Disorders of fibrinogen", section on 'Treatment/prevention of bleeding'.)

•Disseminated intravascular coagulation (DIC) with active bleeding and low fibrinogen. (See "Evaluation and management of disseminated intravascular coagulation (DIC) in adults", section on 'Prevention/treatment of bleeding'.)

•Uremic bleeding. (See "Cryoprecipitate and fibrinogen concentrate", section on 'Uremic bleeding'.)

•Hepatic insufficiency with active bleeding and low fibrinogen. (See "Hemostatic abnormalities in patients with liver disease", section on 'Bleeding'.)

•Postpartum hemorrhage. (See "Overview of postpartum hemorrhage", section on 'Recognize alarm findings and intervene early' and "Disseminated intravascular coagulation (DIC) during pregnancy: Management and prognosis", section on 'Blood products'.)

•Treatment of excessive bleeding and coagulopathy during massive blood loss if hypofibrinogenemia is strongly suspected and testing is not available or lags behind [44,143,145-147,149-160]:

-(See "Cryoprecipitate and fibrinogen concentrate", section on 'Use in specific settings'.)

-(See "Disorders of fibrinogen", section on 'Acute bleeding'.)

Cryoprecipitate — Cryoprecipitate is preferred over plasma to treat documented hypofibrinogenemia when there are no other clotting factor deficiencies and fibrinogen concentrate is not available. (See "Cryoprecipitate and fibrinogen concentrate".)

Differences between cryoprecipitate and fibrinogen concentrate are summarized in the table (table 5).

●Dosing – The typical cryoprecipitate dose, as received from the blood bank, is a pooled product that has been prepared by combining individual cryoprecipitate units derived from 5 to 10 blood donors in a volume of 50 to 200 mL (table 3). This typical dose contains all of the fibrinogen present in one unit of whole blood (approximately 200 to 400 mg), as well as most of the factor VIII, factor XIII, von Willebrand factor (VWF), and fibronectin derived from one unit of FFP in a small volume of 10 to 20 mL (rather than 250 to 300) (table 3 and table 5).

Dosing with a 5-unit bag of cryoprecipitate will increase fibrinogen levels by approximately 35 to 50 mg/dL in a 70 kg adult (each unit of cryoprecipitate raises the fibrinogen concentration by approximately 7 to 10 mg/dL), although this increase may be less if the patient is actively hemorrhaging [161]. Similar to fibrinogen concentrate, the plasma fibrinogen level is monitored after administration to determine if repeat doses are necessary to maintain fibrinogen >150 mg/dL. Higher levels are used in postpartum hemorrhage. (See "Postpartum hemorrhage: Medical and minimally invasive management", section on 'Correct clotting factor deficiencies'.)

●Risks – Risks of cryoprecipitate transfusion are similar to those for FFP (see 'Risks of blood transfusion' below). However, hemolytic transfusion reactions and transfusion-associated circulatory overload (TACO) are less likely than with plasma since the total transfused volume will be substantially less. Also, due to the low volume of plasma in each unit, cryoprecipitate does not need to be ABO matched in adults. However, risk of infection per dose may be higher since the product is pooled from multiple donors. Safety considerations are discussed is a separate topic. (See "Cryoprecipitate and fibrinogen concentrate", section on 'Cryoprecipitate adverse effects'.)

Fibrinogen concentrate — If available, we prefer a fibrinogen concentrate, rather than cryoprecipitate or plasma, to treat hypofibrinogenemia. In continental Europe and Canada, fibrinogen concentrate rather than cryoprecipitate is typically selected to treat hypofibrinogenemia (congenital or acquired), in part because cryoprecipitate is not typically available in these regions [145-147]. Also, fibrinogen concentrate has less risk of infection transmission and immunological complications compared with cryoprecipitate or other blood components [144,145,162]. However, fibrinogen concentrate has higher up-front costs than cryoprecipitate [144,145].

Proponents of fibrinogen concentrate argue that the natural baseline concentration of fibrinogen is relatively low, and there are no fibrinogen stores to be mobilized. Therefore, fibrinogen is the first coagulation protein to become critically low during intraoperative bleeding [149]. A 2020 meta-analysis included 13 trials with 900 patients who had author-defined low fibrinogen level or clinically significant blood loss during any type of surgery [163]. In this meta-analysis, blood loss was reduced in the first 12 postoperative hours in patients who received fibrinogen concentrate compared with those who received placebo, but the mean difference was only -135 mL (95% CI -183 to -87 mL), and results were inconsistent for other clinically important outcomes such as survival.

However, guidelines do not suggest aiming for supranormal fibrinogen levels, and they do not recommend prophylactic administration of fibrinogen concentrate in individuals with normal fibrinogen levels [145,146,164,165].

●Dosing – The dose of fibrinogen concentrate is calculated according to the target fibrinogen concentration. (See "Disorders of fibrinogen", section on 'Fibrinogen concentrate: Dosing and monitoring'.)

Dosing is typically monitored with viscoelastic testing (VET) and monitoring of plasma fibrinogen level [155,156]. However, use of VET to determine when and how to supplement fibrinogen in patients with intraoperative bleeding has been particularly challenging [166]. (See 'Point-of-care tests' above.)

●Risks – Thromboembolic complications can occur, particularly in pregnant patients. Overcorrection of fibrinogen deficiency should be avoided to minimize this risk. While caution is warranted, most studies have not reported increased risk of thrombotic events [153,157].

Risks of blood transfusion — Potential complications of blood component transfusion (including RBCs, plasma, platelets and cryoprecipitate) consist of hemolytic transfusion reactions, transfusion-related acute lung injury (TRALI) [167], transfusion-related circulatory overload (TACO), transfusion-transmissible infections (bacterial, viral, or parasitic (table 6)), transfusion-associated graft-versus-host disease (TA-GVHD), and transfusion-related immunomodulation that may lead to postoperative infection and other potential morbidities [124]. Alloimmunization leading to reduced availability of compatible blood components can also occur. Notably, the incidence of TRALI and TACO may be higher in perioperative patients compared with nonsurgical patients [167].

These complications are discussed elsewhere:

●(See "Indications and hemoglobin thresholds for RBC transfusion in adults", section on 'Risks and complications of transfusion'.)

●(See "Platelet transfusion: Indications, ordering, and associated risks", section on 'Complications'.)

●(See "Clinical use of plasma components", section on 'Risks'.)

●(See "Cryoprecipitate and fibrinogen concentrate", section on 'Cryoprecipitate adverse effects'.)

Massive transfusion may result in additional complications (eg, citrate toxicity with hypocalcemia, hyperkalemia, acidosis, hypothermia), which are discussed separately. (See "Massive blood transfusion".)

The approach to a patient with an acute transfusion reaction is discussed separately [168,169]. (See "Approach to the patient with a suspected acute transfusion reaction".)

Evaluation of specific complications is discussed in separate topics:

●(See "Immunologic transfusion reactions".)

●(See "Transfusion-related acute lung injury (TRALI)".)

●(See "Transfusion-associated circulatory overload (TACO)".)

●(See "Transfusion-transmitted bacterial infection".)

●(See "Blood donor screening: Laboratory testing", section on 'Viruses'.)

●(See "Transfusion-associated graft-versus-host disease".)

USE OF CLOTTING FACTORS — Clotting factors have been administered to selected patients with persistent or severe intraoperative (or preoperative or postoperative) bleeding due to various causes of impaired coagulation. Ideally, any clotting factor administered should treat the specific deficiency. For example, fibrinogen concentrate may be administered to treat an isolated fibrinogen deficiency with fibrinogen concentration <150 mg/dL in a patient with clinically significant bleeding, as noted above. (See 'Fibrinogen concentrate' above.).

Intraoperative use of other clotting factors such as prothrombin complex concentrate (PCC; activated or unactivated) or factor VIII inhibitor bypassing agent (FIEBA), recombinant activated factor VII (rFVIIa) is discussed below. (See 'Prothrombin complex concentrates (PCCs)' below and 'Recombinant activated factor VII (rFVIIa)' below.)

Intraoperative uses of hemostatic agents such as antifibrinolytics or desmopressin (DDAVP) are discussed in a separate topic. (See "Perioperative blood management: Strategies to minimize transfusions", section on 'Systemic hemostatic agents'.)

Prothrombin complex concentrates (PCCs)

Unactivated PCC

●Indications and uses — The two indications approved by the US Food and Drug Administration (FDA) for PCC is reversal of warfarin for emergency invasive procedures or active bleeding on warfarin. While the prothrombin time and international normalized ratio (PT/INR) may "correct" the patient may still have ongoing abnormalities of coagulation.

Advantages of using a PCC rather than plasma include rapid administration and small volume. For initial and sustained effect and for both plasma and PCC, concomitant administration of vitamin K is required. Compared with plasma, PCC carry less risk of volume overload and avoid transfusion reactions [44,149,150,170-181]. (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'.)

•Treatment of vitamin K antagonist anticoagulation – A four-factor PCC should be used; this contains factors II, VII, IX and X, heparin, antithrombin, protein C and S, and albumin. (table 7). PCCs are typically used to treat intraoperative bleeding associated with warfarin or another vitamin K antagonist, in combination with vitamin K [170]. (See "Management of warfarin-associated bleeding or supratherapeutic INR", section on 'PCC products' and "Reversal of anticoagulation in intracranial hemorrhage", section on 'Warfarin'.)

•Reversal of factor Xa inhibitors – A four-factor PCC can be used to treat life-threatening bleeding in a patient actively anticoagulated with a factor Xa inhibitor (apixaban, rivaroxaban, edoxaban). Assessment of active anticoagulation and discussion of PCC versus andexanet alpha is presented separately. (See "Management of bleeding in patients receiving direct oral anticoagulants", section on 'Factor Xa inhibitors'.)

•Treatment of intractable bleeding in selected surgical procedures – A PCC product may be reasonable in selected surgical patients with intractable coagulopathy and diffuse bleeding (eg, cardiac surgery with cardiopulmonary bypass [CPB], liver transplantation, trauma surgery), particularly if intolerance of high FFP transfusion volume is a factor. These uses of PCC and fibrinogen concentrate are off label in the United States.

-Cardiac surgery – Off-label intraoperative use of PCCs has been reported for treatment of patients with intractable coagulopathic bleeding after cardiac surgery with CPB [44,46,85,149,150,171-187]. Randomized trials and observational studies in cardiac surgical patients have noted reductions in blood transfusions in patients with excessive bleeding and coagulopathy after CPB who received four-factor or three-factor PCC compared with those receiving plasma [85,177,178,180,181,187]. However, prospective data regarding the safety, efficacy, and dosing of PCCs in this setting are limited. Other sources of coagulopathy (eg, surgical sources, thrombocytopenia, hypofibrinogenemia, platelet dysfunction, disseminated intravascular coagulation [DIC]) should be sought and treated. (See "Achieving hemostasis after cardiac surgery with cardiopulmonary bypass", section on 'Prothrombin complex concentrate products'.)

-Liver transplantation – In a propensity score-matched retrospective study of 60 pairs of patients undergoing liver transplantation, PCC use was associated with significantly decreased red blood cell (RBC) and plasma transfusion requirements compared with no PCC use, and no thromboembolic events were noted [188].

-Trauma surgery – In trauma patients with findings of trauma-induced coagulopathy, limited data (mostly observational) suggest that administration of four-factor PCC, alone or in combination with fibrinogen concentrate or plasma, can reduce transfusion of RBCs and other blood components [189-193]. (See "Ongoing assessment, monitoring, and resuscitation of the severely injured patient", section on 'Other agents' and "Ongoing assessment, monitoring, and resuscitation of the severely injured patient", section on 'Management'.)

●Dosing – The dose of a PCC product is tailored to the individual patient's needs based on clinical indications and laboratory testing, but typically 1000 to 2000 units is administered. (See "Management of warfarin-associated bleeding or supratherapeutic INR", section on 'PCC products'.)

Ideally, point-of-care (POC) viscoelastic testing (VET) such as thromboelastography (TEG) or rotational thromboelastometry (ROTEM) is obtained to monitor overall hemostatic function and supplement information provided by standard laboratory tests (eg, prothrombin time [PT], international normalized ratio [INR], activated partial thromboplastin time [aPTT], fibrinogen level). (See "Etiology and diagnosis of coagulopathy in trauma patients", section on 'Diagnosis' and 'Point-of-care tests' above.)

●Risks – Data for intraoperative safety of PCC are limited [59,146,171,177,182,187,194]. Risk for thromboembolic events may be more likely with repeat or excessive dosing of either four-factor and three-factor PCC, a risk that may extend well into the postoperative period [195]. Also, four factor PCC products contain small amounts of heparin and should not be used in an individual with a known history of heparin-induced thrombocytopenia. (See "Plasma derivatives and recombinant DNA-produced coagulation factors", section on 'PCCs' and "Management of warfarin-associated bleeding or supratherapeutic INR", section on 'PCC risks'.)

Activated PCC — In contrast with standard three- or four-component PCCs, an activated PCC (aPCC; FEIBA) contains activated factor VII (table 7). Due to the greater prothrombotic risk compared with PCC and lack of clinician familiarity, aPCC is not commonly used in the intraoperative setting [171,194]. However, FEIBA may be administered in selected individuals such as those with bleeding due to a factor VIII inhibitor, or bleeding associated with fondaparinux or dabigatran when a specific reversal agent is not available. (See "Plasma derivatives and recombinant DNA-produced coagulation factors", section on 'Recombinant factor VIIa' and "Management of bleeding in patients receiving direct oral anticoagulants", section on 'Dabigatran reversal' and "Fondaparinux: Dosing and adverse effects", section on 'Bleeding/emergency surgery'.)

Recombinant activated factor VII (rFVIIa)

●Indications and uses

•Factor inhibitors – 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, as discussed separately. (See "Treatment of bleeding and perioperative management in hemophilia A and B", section on 'Inhibitors'.)

•Treatment of life-threatening bleeding in selected surgical procedures – In rare instances when intractable bleeding that is potentially life-threatening persists after cardiac or other major surgery, off-label administration of rFVIIa has been reported in attempts to promote clotting and reduce transfusion requirements, after all other efforts have failed [44,196-199]. Similar to off-label use of PCCs, primary causes of coagulopathy should always be sought and treated before considering administration of rFVIIa. Failure to treat the primary coagulation disorder increases the likelihood of inadequate response to the initial dose of rFVIIa [200-202], and may encourage use of higher doses and greater risk of thrombosis [203,204]. (See "Recombinant factor VIIa: Administration and adverse effects", section on 'General approach to administration'.)

Information regarding efficacy of rFVIIa in this setting is largely anecdotal. Systematic reviews have not found a great impact on morbidity and mortality, although transfusion requirements may be reduced [203,205-207]. In cardiac surgical patients, one study reported that a median dose of 13.3 mcg/kg resulted in low overall blood transfusions in cardiac surgical patients [198]. Administration of rFVIIa earlier in the postbypass period when intractable bleeding was identified after transfusion of one or fewer units of RBCs resulted in a relatively lower total dose of rFVIIa (12.2 [9.7-16.4] mcg/kg), whereas higher doses were necessary (18.0 [11.8 to 29.0] mcg/kg) after five or more units of RBCs had been transfused [208]. However, a median of two additional blood components were necessary after administration of rFVIIa regardless of the total dose. (See "Recombinant factor VIIa: Administration and adverse effects", section on 'Off-label uses'.)

●Dosing – Dosing practices vary widely because data are lacking regarding optimal dosing and there are no laboratory tests to monitor drug effect or efficacy. We dose rFVIIa cautiously in small incremental doses of 10 mcg/kg up to a total dose of up to 90 mcg/kg. Stocking the smaller 1 mg vials of rFVIIa facilitates this incremental approach. (See "Recombinant factor VIIa: Administration and adverse effects", section on 'General approach to administration'.)

●Risks – High thromboembolism rates >20 percent have been reported in retrospective evaluations of registries for refractory bleeding cases [201-203]. Arterial thromboembolic events have been noted in some trials, particularly in patients with intracranial hemorrhage and those undergoing cardiac surgery [203,205-207]. Thromboembolic complications are more likely with dose escalation, or in the presence of stagnant flow or devices such as extracorporeal membrane oxygenation (ECMO) [44]. Conversely, risk of thrombotic complications may be reduced when lower doses (eg, 10 to 30 mcg/kg) are administered [203,209]. Off-label intraoperative use of rFVIIa is also associated with increased mortality and morbidity (eg, renal failure), especially with administration of higher doses or in older patients [149,196,203,210,211].

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

●Prepare for large surgical blood loss

•Elective surgery – We obtain preoperative typing and crossmatching and determine whether blood components should be available in the operating room before incision. (See 'Elective surgery with risk for significant blood loss' above.)

•Emergency surgery with possible massive transfusion – Early communication is necessary to activate a massive transfusion protocol. We transfuse red blood cells (RBCs), plasma, and platelets in approximately equal ratios (1:1:1). (See 'Emergency surgery with possibility of massive blood transfusion' above.)

●Technical considerations – Establish intravenous access. Adhere to protocols for patient identification. Use compatible fluids. Use a blood warmer for cold and previously thawed components. (See 'Technical aspects of blood transfusion' above.)

●Assess blood loss and bleeding risk – Blood loss is assessed visually and quantified from blood suction canisters, surgical sponges, and drapes. (See 'Estimating blood loss' above and 'Intraoperative diagnostic testing' above.)

•Standard tests – Includes hemoglobin, prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (aPTT), platelet count, and fibrinogen concentration. (See 'Standard tests' above.)

•Point-of-care (POC) tests – POC viscoelastic testing (VET) of coagulation (eg, thromboelastography [TEG], rotational thromboelastometry [ROTEM]) may be used for rapid assessment of causes of coagulopathy and responses to interventions (figure 1 and figure 2 and table 1 and table 2). POC platelet aggregometry is rarely used. (See 'Tests of coagulation function' above.)

●Transfusion decisions – We use protocols or algorithms to guide transfusion decisions (table 3). For patients with significant coagulopathic bleeding, we use VET (if available), rather than standard coagulation tests. Estimates of blood loss, signs of anemia, and intractable microvascular bleeding are also considered. (See 'General principles for transfusion decisions' above.)

•Restrictive strategy for RBCs – For most surgical patients without significant ongoing bleeding, we suggest a restrictive strategy, transfusing for hemoglobin <7 g/dL or <8 g/dL rather than higher levels (Grade 2C). The exact restrictive threshold depends on the clinical setting. This includes autologous, salvaged, or allogeneic RBCs. However, decisions are individualized; a hemoglobin threshold of <9 g/dL may be used in selected patients with signs of myocardial or other organ ischemia. (See 'Red blood cells' above.)

•Platelets – We typically maintain a platelet count >50,000/microL (>100,000/microL when ocular central nervous system bleeding is present or likely). Each dose (one apheresis unit or one pool of whole blood-derived platelets) increases the platelet count by 30,000/microL to 50,000/microL (less if platelets are being consumed) (table 3). (See 'Platelets' above.)

•Plasma – Plasma can be used for emergency surgery with severe bleeding and deficiency of multiple coagulation factors, particularly if intracranial hemorrhage is present (table 4). Dosing depends on the degree of deficiency. (See 'Plasma' above.)

•Cryoprecipitate or fibrinogen concentrate – We aggressively correct hypofibrinogenemia (<150 mg/dL) if there is active and ongoing bleeding. Cryoprecipitate is more commonly used in the United States and United Kingdom; fibrinogen concentrate is more often available in continental Europe and Canada. Risks are lower with fibrinogen concentrate (table 5). (See 'Cryoprecipitate or fibrinogen concentrate' above.)

●Transfusion risks – (See 'Risks of blood transfusion' above and "Approach to the patient with a suspected acute transfusion reaction".)

●Clotting factors

•Prothrombin complex concentrates (PCCs) – PCCs are used for emergency treatment of warfarin, along with concomitant administration of vitamin K (table 7). PCC or andexanet alfa can be used for emergency reversal of factor Xa inhibitors. Off-label uses such as intractable coagulopathy and diffuse bleeding after cardiopulmonary bypass (CPB) may be reasonable (table 7). Other causes of intractable microvascular bleeding should be treated before considering a PCC. (See 'Unactivated PCC' above.)

Activated PCC (aPCC; FEIBA) contains activated factor VII and is not commonly used intraoperatively due to greater prothrombotic risk than unactivated PCCs. (See 'Activated PCC' above.)

•Recombinant activated factor VII (rFVIIa) – rFVIIa may be used off-label for intractable life-threatening coagulopathic bleeding after CPB. (See "Achieving hemostasis after cardiac surgery with cardiopulmonary bypass", section on 'Recombinant activated factor VII'.)