Chapter 2: Transfusion of Blood Components and Derivatives in the Obstetric Intensive Care Patient

Obstetric hemorrhage remains one of the leading causes of maternal death in the United States, often necessitating the transfusion of blood products as a lifesaving measure. More commonly, the practitioner encounters less acute situations and must decide which blood products, if any, are appropriate for the patient. In this chapter, we will address the blood products currently available for transfusion, the indications for their use, and potential risks. We will also discuss alternatives and techniques to avoid transfusion, including available colloid solutions, use of the “autologous transfusion device,” and acute normovolemic hemodilution (ANH).

In modern obstetric practice, transfusion of whole blood is uncommon. Typically, whole blood is separated into its components (red blood cells [RBCs], platelets, fibrinogen, and other clotting factors) and stored. Blood component therapy allows treatment of specific derangements in the patient’s blood. The potential benefits of administering blood products must be weighed against the potential risks, both short and long term.

Transfusion risks are typically categorized into infectious and noninfectious complications. Adverse events are reported to complicate approximately 10% of the 14.2 million red cell units administered annually in the United States. Fortunately, less than 0.5% of these are serious reactions. Nevertheless, death related to transfusion may be significantly underreported.¹ Patient concerns regarding transfusion risks have traditionally focused on the spread of viral infectious diseases. However, 40% to 50% of deaths related to transfusion result from noninfectious complications and bacterial contamination of platelets.² The leading causes of allogeneic blood transfusion-related mortality in the United States in the order of number of reported deaths are transfusion-related acute lung injury (TRALI), ABO and non-ABO hemolytic transfusion reactions (HTR), and transfusion-associated sepsis (TAS).³

Infectious Transfusion Risks

Improvements in screening strategies for prospective donors and testing of donated blood products have significantly reduced the likelihood of viral infection from contaminated blood. In the United States, each unit of donated blood is tested for hepatitis B surface antigen and core antibody, hepatitis C antibody, HIV and human T-cell leukemia virus (HTLV) types 1 and 2 antibodies, West Nile virus, and syphilis. Nucleic acid testing is also performed for HIV-1 and hepatitis C, as it detects viral genome before an antibody response develops. Table 2-1 outlines infectious risks from transfusion and their estimated frequency. Composite risk for HIV, hepatitis B and C, and HTLV infection from transfusion is estimated to be less than 1 in 30,000.

Other infectious diseases can be transmitted through blood products but are not universally screened by direct testing of the blood product. Rather, screening of the individual donor is performed by a detailed questionnaire designed to identify persons at risk for harboring specific diseases. Some examples of these diseases include cytomegalovirus, Chagas disease, babesiosis, malaria, Creutzfeldt-Jakob disease, hepatitis A, Lyme disease, Epstein-Barr virus, and human herpes viruses. Alarmingly, 1 to 2 per 100 donations test positive for hepatitis G virus, SEN virus, and transfusion-transmitted virus. The significance of these viruses remains to be determined.²

Clinically significant cytomegalovirus (CMV) infections usually occur in immunocompromised patients. However, a small but significant portion of persons in the population has never been exposed to CMV and has no natural immunity to it. Although CMV infection in the adult is usually a benign, subclinical process, primary maternal infection confers a 40% risk of in utero transmission and can have devastating effects. Therefore, CMV seronegative, leukoreduced blood products should be administered to the seronegative pregnant patient.

Bacterial contamination of blood products, particularly platelets, accounts for 17% to 22% of infectious deaths related to transfusion, making this one of the leading causes.⁶

Noninfectious Transfusion Risks

Noninfectious transfusion risks are more common than infectious risks and are often underrecognized and underreported. Noninfectious risks of transfusion can be further categorized as hemolytic and nonhemolytic in nature.

Hemolytic Transfusion Reactions

Acute Hemolytic Transfusion Reaction

Over 250 red cell antigens have been identified, any of which can lead to a hemolytic transfusion reaction when administered to incompatible recipients. Testing of blood type, antibody screen, and crossmatch is performed to avoid transfusion of incompatible blood. Approximately 0.2% to 0.6% of the general population is sensitized.¹ Acute hemolytic reactions occur with exposure to incompatible ABO types at a rate of 1 in 12,000 to 19,000 units transfused. Clinically, the patient develops sudden onset of fever, chills, flank and back pain, circulatory collapse, and microangiopathic thromboses. This type of reaction is most commonly the result of error.

Delayed Hemolytic Transfusion Reaction

Delayed hemolytic reactions occur as a result of exposure to incompatible human leukocyte antigen (HLA) and complicate 1 in 1000 to 9000 red cell transfusions.⁷ HLAs are present on all cells except mature red blood cells. HLA alloimmunization occurs in response to a prior exposure to incompatible blood or from prior pregnancy. Because these antigens are present on tissues apart from red cells, the hemolytic reaction occurs extravascularly and is less severe than reactions to incompatible red cell antigens.

Nonhemolytic Transfusion Reactions

The nonhemolytic transfusion reaction is much more common (1 in 100). Usually characterized by febrile or urticarial reactions, more serious reactions such as transfusion-related lung injury and graft-versus-host disease can also develop.

Transfusion-Related Acute Lung Injury

Transfusion-related acute lung injury (TRALI) is defined as acute lung injury which develops within 6 hours of transfusion, in the absence of left atrial hypertension or other risk factors for acute lung injury (ie, pneumonia, sepsis, aspiration, fractures, and pancreatitis).⁸ TRALI complicates at least 1 in 5000 transfusions with a 6% risk of mortality and is believed to be the most common cause of mortality related to transfusion.⁹ Clinically, patients develop sudden onset of respiratory distress, pulmonary edema, fever, and hypotension. The etiology is unclear; however, the “two-hit” hypothesis for the pathogenesis of TRALI proposes neutrophil sequestration and priming in the recipient followed by activation of recipient neutrophils by a factor in the blood product.¹⁰ Female gender and increased parity of the donor are associated with an increased risk of TRALI. A multicenter cohort study showed that plasma or whole blood from female donors was one of the 3 major blood component risk factors for TRALI.¹¹ If TRALI is suspected, the transfusion should be immediately discontinued and reported to the blood bank. Treatment is primarily supportive and may require ventilatory support. Unlike acute respiratory distress syndrome (ARDS), TRALI typically resolves rapidly and is less likely to be fatal. It is important to consider TRALI in the differential diagnosis of acute pulmonary edema and avoid use of diuretics, as it may worsen outcome.^12,13 Prevention of TRALI involves deferring donors implicated in a case of TRALI and restricting transfusion of plasma products from multiparous women which are most likely to contain antileukocyte antibodies.⁸

Febrile Reactions

Fever associated with the administration of leukoreduced blood products occurs in 0.1% to 1% people annually and is more common if the product is not leukoreduced.¹⁴ The febrile response is hypothesized to be the result of cytokine release from white blood cells in the blood product. Utilization of leukoreduced blood products and prophylactic antipyretic therapy dramatically decreases the likelihood of a febrile reaction.¹

Allergic Reactions

Allergic reactions manifest primarily as urticaria, itching, flushing, rash, or angioedema without fever. These types of responses are common and can be quite severe, including anaphylaxis. Antihistamines can be administered prophylactically. With minor reactions, intravenous antihistamines may allow completion of the transfusion. More severe reactions require cessation of the transfusion.

Alloimmunization can result in platelet antibodies which may prevent therapeutic response in the thrombocytopenic patient who receives platelet transfusion. Rarely, graft-versus-host disease can occur following transfusion of some blood components (platelets, white blood cells, etc) into an immunocompromised individual.

Transfusion-Associated Graft-Versus-Host Disease

This rare complication of transfusion primarily affects immunosuppressed individuals and carries a high mortality rate (>90%). Irradiation of blood products may eliminate this risk.¹⁴

Miscellaneous Complications

Massive transfusion, defined as replacement of an entire blood volume in 24 hours or administration of more than 10 units in a few hours, carries particular risks to the patient. The citrate component in stored blood products binds with calcium and this leads to hypocalcemia when administered in large amounts. Alkalosis is also common following massive transfusion, as is hypothermia, potassium disturbances, and decreased 2,3-DPG. Prewarming the infused blood and maintaining normothermia of the patient can minimize some of these effects. Monitoring acid-base balance as well as potassium and calcium levels is essential in the setting of massive transfusion. Coagulation defects are also common when patients receive large amounts of blood products; therefore, monitoring and correction of clotting status are warranted.

Transfusion-Related Immunomodulation

The transfusion of blood products does appear to suppress the host immune system with both beneficial and detrimental effects. Patients receiving transfusions have lower rates of renal transplant rejection and improvement in certain autoimmune disease activity, that is, rheumatoid arthritis.¹ However, more recent studies suggest that patients, particularly surgical and trauma patients, receiving blood transfusions have increased rates of mortality, postoperative infections, and multiorgan system failure.^2,4,15,16 This has prompted an ongoing reevaluation of the thresholds for transfusion in critically ill and surgical patients.

Red cell transfusions are performed primarily with the intent to improve oxygen delivery. Recent data suggest that the benefit of transfusion may not be self-evident in the critically ill or surgical patient without active hemorrhage. In a large study of critically ill patients, lowering the transfusion goal from 10 to 7 g/dL with a transfusion trigger of 7 g/dL failed to show benefit from more liberal transfusion. Younger (<55 years) and less critically ill patients, however, had a survival benefit in the restrictive transfusion group. This approach has also been supported in a pediatric critically ill population, but has not been studied in pregnant women.^{17,18, 19} A recent Cochrane review of 19 trials involving 6264 patients showed that restrictive transfusion strategies reduced the risk of receiving a RBC transfusion by 39%. There was no increase in adverse outcomes (ie, mortality, cardiac events, myocardial infarction, stroke, pneumonia, and thromboembolism) compared to more liberal strategies and were associated a statistically significant reduction in hospital mortality (RR 0.77, 95% CI 0.62-0.95) but not 30-day mortality (RR 0.85, 95% CI 0.70-1.03). The use of restrictive transfusion strategies did not reduce functional recovery, hospital or intensive care lengths of stay.²⁰ A less restrictive strategy in postoperative patients with hemoglobin less than 8 g/dL or symptoms of acute blood loss anemia does not improve postoperative recovery.²¹ The exact threshold for transfusion in a hemodynamically stable patient without evidence of active bleeding remains to be defined. Table 2-2 summarizes expected clinical findings with increasing blood loss.

Those blood products most commonly used in pregnancy are generally subdivided into cellular or plasma components (Table 2-3).

Red Blood Cells

• Most patients requiring replacement of red blood cells should receive packed red blood cells (PRBC).

• One unit of PRBCs contains roughly 250 mL of RBCs, 50 mL of plasma, and has a hematocrit of approximately 80%. The decreased plasma volume of packed cells minimizes the risk of fluid overload.

• Transfusion of 1 unit of PRBCs into a 70-kg person will usually increase the hemoglobin level by 1 g/dL.

• Like whole blood, PRBCs have a shelf life of approximately 6 weeks when stored at 1°C to 6°C.

• Frozen RBCs can be stored at –70°C for years, but the freezing process destroys white blood cells (WBCs) which may be present in the unit of blood.

• When WBCs have been removed from a unit of blood, the blood is considered to be “leukocyte-poor” and poses lower risk of febrile transfusion reactions.

• The precise threshold for transfusion is not known, particularly in gravidas. Patients who are actively hemorrhaging and displaying cardiovascular instability or evidence of fetal compromise should be considered candidates for RBC transfusion.

Autologous Blood

Autologous transfusion is the collection and reinfusion of the patient’s own RBCs. Therefore, donor and recipient are identical. Exclusive or supplemental use of autologous blood should reduce many transfusion-related complications and is particularly useful for the patient with multiple antibodies. In both pregnant and nonpregnant patients, perioperative autologous blood donation has been demonstrated to reduce the likelihood of receiving allogeneic blood products.^{22,23, 24} Autologous blood donation appears to be a safe procedure during pregnancy.^25,26 However, the use of autologous blood does not eliminate risk to the patient. Concerns remain regarding bacterial contamination of stored blood and human error. The indications for transfusing donated blood should be the same as for allogeneic blood. The American Association of Blood Bank standards do not permit rollover of unused autologous units into the general blood supply, as the donors are not considered “volunteers." Unused units will be discarded.

Patients with an active seizure disorder or significant cardiopulmonary disease are not candidates for autologous blood donation.

The guidelines for autologous blood donation during pregnancy are as follows:

• A minimum predonation hemoglobin of 11 g/dL.

• Because RBCs may be refrigerated in liquid form for only 6 weeks, initiation of autologous blood donation generally occurs not earlier than 6 weeks before their anticipated use. The last donation should be planned at least 2 weeks before the estimated date of delivery.

• One week should elapse between donations.

• Autologous blood should be used selectively. The unnecessary transfusion of autologous blood increases the risk of circulatory overload, exposure to bacterial contamination, and human error.

• Because of the special logistics of autologous blood, autologous donor candidates should be aware that this technique is more costly than allogeneic transfusions and may not be covered by their health insurer.

• Patients should be aware that autologous blood donation does not completely eliminate the possibility of allogeneic transfusion.

• Preoperative donation may also lead to anemia and an increased risk for postoperative transfusion. Consideration should therefore be given to maximizing the hemoglobin with supplemental iron, erythropoietin, folate, and vitamin B₁₂.

Platelet Concentrates

Platelets for infusion can be prepared either by separating them from whole blood of multiple donors and pooling them together into a single unit, or by apheresis of platelets from a single donor. The apheresis method results in a unit equivalent to 4 to 6 pooled units from whole blood.²⁷ Platelets can be stored for 5 days.

Platelet concentrates are indicated for the treatment of hemorrhage due to thrombocytopenia or platelet dysfunction (thrombocytopathia). The cause of thrombocytopenia or thrombocytopathia must be determined. For example, in the presence of immune thrombocytopenic purpura (ITP), where platelets are destroyed via an antibody-mediated process, corticosteroids rather than platelets probably represent the best initial therapy. Additionally, patients taking aspirin preparations can experience potentially serious bleeding despite normal platelet counts. When ordering a platelet transfusion, the following should be considered:

• In pregnant patients, thrombocytopenia is considered to be present when the platelet count falls below 100,000/mm³. Bleeding following major surgery or trauma rarely occurs when the platelet count is 50,000/mm³ or greater, assuming normal platelet function. When the platelet count ranges from 20,000 to 50,000/mm³, bleeding with major surgery or trauma can occasionally occur. Platelet transfusion may be performed prophylactically in nonbleeding patients with platelet counts of 10,000 to 20,000 platelets/mm³ or less.²⁷ When the platelet count falls to 10,000/mm³, bleeding with trauma or surgery is more likely. Spontaneous bleeding can occur once the platelet count drops below 10,000/mm³.

• Among patients receiving massive transfusions within a short period of time, dilutional thrombocytopenia can occur. Following replacement of one blood volume, 35% to 40% of a patient’s platelets usually remain. Ideally, platelet replacement therapy in the setting of massive hemorrhage should be guided by platelet counts.

• One unit of apheresis platelets contains, on average, 4.2 × 10¹¹ platelets, an amount roughly equivalent to 4 to 6 pooled units. Therefore, an average platelet concentrate (pooled or apheresis) will increase the platelet count in a 75-kg patient by approximately 7000 to 10,000 platelets/mm³ 1 hour posttransfusion.²⁷ Therefore, the platelet count can be assessed almost immediately following completion of the transfusion.

• Platelet concentrates contain sufficient numbers of serum-bound RBCs to cause alloimmunization to red cell antigens. Therefore, the possibility of Rh immunization by red cells from Rh-positive donors should be considered in Rh-negative female recipients.

• Platelet transfusion is contraindicated in thrombotic thrombocytopenic purpura (TTP) and will be ineffective in the setting of increased platelet destruction (heparin-induced thrombocytopenia, idiopathic thrombocytopenic purpura).

Fresh-Frozen Plasma

Fresh-frozen plasma (FFP) is plasma extracted from whole blood or plasma apheresis within 6 hours of collection and then frozen. A typical unit of FFP contains 250 mL of fluid and 700 mg of fibrinogen, as well as all plasma proteins and clotting factors. FFP is indicated to correct deficiencies of multiple clotting factors in bleeding patients. Clotting factor deficiencies can arise from liver disease, vitamin K deficiency, massive hemorrhage, or disseminated intravascular coagulation. FFP may also be used for specific factor deficiencies (factors II, V, VII, IX, X, and XI) when specific component therapy is not available, and can provide rapid reversal of warfarin. Warfarin causes a deficiency of the vitamin K–dependent factors (II, VII, IX, and X). While vitamin K will eventually reverse this deficiency, FFP can affect a more rapid recovery.

• One unit of FFP will typically increase the fibrinogen level by approximately 10 to 15 mg/dL. When FFP is indicated, 15 mL/kg is a reasonable guideline for initiation of FFP therapy (target serum fibrinogen level is ~100 mg/dL).

• It should be kept in mind that 20 to 30 minutes are required to thaw FFP in the blood bank.

• Anti-ABO antibodies are not removed from FFP, therefore ABO compatibility should be considered.

• When only factor VIII, von Willebrand factor, or fibrinogen is needed, cryoprecipitate is a more appropriate therapeutic choice. Inappropriate uses of FFP include use of this blood component for volume expansion or as a nutritional supplement.

Cryoprecipitate

Cryoprecipitate is extracted from thawed FFP. The product is a cold insoluble fraction of FFP which precipitates under these conditions. Cryoprecipitate is rich in factor VIII (80-120 units) and fibrinogen (200 mg) and also contains von Willebrand factor and factor XIII. One unit of cryoprecipitate will raise the fibrinogen level by the same amount as 1 unit of FFP (10-15 mg/dL). However, as 1 unit of cryoprecipitate consists of only 40 mL of fluid, it more efficiently raises the fibrinogen level than does a 250-mL unit of FFP. Indications for the use of cryoprecipitate include the treatment of von Willebrand disease, factor VIII deficiency, and fibrinogen deficiency as may occur in the setting of hemorrhage. ABO compatibility is not an issue with cryoprecipitate administration.²⁸

Recombinant Factor VIIA

Recombinant factor VIIA (rFVIIa, NovoSeven) is FDA approved for use in patients with hemophilia A or B or congenital factor VII deficiency. However, its off-label use has been widely reported in the setting of trauma, cardiac surgery, and in attempts at reduction of perioperative blood loss and management of obstetric hemorrhage. Its proposed mechanism of action involves binding to the surface of activated platelets to promote factor X activation and thrombin generation.²⁹ A systematic review of off-label indications for rFVIIa showed no difference in survival,³⁰ but no randomized, controlled trials have been performed in obstetric settings. The incidence of thromboembolic events associated with use of rFVIIa has ranged from 1% to 2% to as high as 9.8%,³¹ and a recent study showed an increased risk of arterial thrombosis.³² No definitive recommendations exist for its use or optimal dosage in obstetric hemorrhage management. It is currently not recommended as a first-line therapy but may be considered when conventional methods have failed to control bleeding. A typical bolus dose of rFVIIa is 60 to 90 mg/kg, which may be repeated within 30 minutes, if there is insufficient clinical improvement. It should be used with caution in the presence of sepsis and should not delay hysterectomy, if indicated.³³

Intravenous fluids containing particles that will not pass through a semipermeable membrane and are larger than 10,000 Da are known as colloids. Compared to crystalloid solutions, colloids are more expensive, less readily available, and may be associated with anaphylactoid reactions. Colloids tend to produce greater elevations in colloid oncotic pressure than crystalloids. They also produce greater increases in plasma volume and deplete extracellular fluid. Patients receiving colloid solutions must be adequately prehydrated with crystalloids. The properties of the available colloid solutions are outlined in Table 2-4.

Albumin

Albumin solutions may rapidly restore intravascular volume, especially if serum albumin levels are less than 2 g/dL. Use should be limited to patients with decreased plasma volume and adequate extracellular volume. Albumin is available in concentrations of 5% or 25%. Five percent solutions are generally limited to patients with burns or peritonitis and have limited use in acute situations. When 25 g of albumin are infused, intravascular volume will increase by roughly 450 mL over 60 minutes as a result of its oncotic activity. However, the benefits are only transient and may result in complications such as pulmonary edema, if administered excessively. Supplemental albumin is rapidly redistributed throughout the extracellular space, disappearing from the circulation at a rate of up to 8% per hour. In the setting of shock or sepsis, the rate can approach 30% per hour.

Dextran

Dextran is a glucose polymer solution available with polymers having mean molecular weights of 40,000 (dextran 40) or 70,000 (dextran 70). A 6% dextran 70 solution is used for indications similar to those of 5% albumin. Dextran 40 is rarely used for acute volume expansion. A 500-mL infusion of dextran produces intravascular volume expansion of 1050 mL over 2 hours and improves capillary blood flow by reducing viscosity and red cell aggregation. As with albumin, the effects of dextran are temporary and may be associated with pulmonary edema if used too aggressively. Both forms are degraded into glucose.

In doses exceeding 20 mL/kg/24 h, dextran may also interfere with platelet function by impeding clotting factor activation and by binding with fibrin to produce less stable clots. Anaphylactoid reactions complicate 1 in 3300 dextran infusions. Interference with laboratory crossmatching of blood has also been described. Therefore, blood typing and crossmatching should be performed prior to its administration.

Hetastarch

Hydroxymethyl starch is a synthetic molecule available as a 6% solution in normal saline (Hespan). Like albumin and dextran, it possesses considerable oncotic activity and can induce intravascular fluid expansion. However, hetastarch increases colloid oncotic pressure more effectively than albumin and lasts 24 to 36 hours. The recommended dose is 20 mL/kg/24 h. Hetastarch may also prolong prothrombin and partial thromboplastin times, decrease platelet counts, and reduce clot tensile strength. Therefore, it should be used cautiously in patients who may have a coagulopathy. Hetastarch may also artifactually increase serum amylase levels. Hextend is a newer hetastarch 6% solution in a physiologic electrolyte solution. It may offer an advantage over Hespan in that the lower molecular weight may be associated with less risk for coagulation abnormalities.

The immediate recycling of blood lost during surgery or following trauma has become an accepted treatment modality. Autologous blood, collected preoperatively or intraoperatively, offers a variety of advantages over allogeneic blood. As a perfectly compatible source, unstored autologous blood essentially eliminates the risk of viral disease transmission or isoimmunization. However, the use of intraoperative cell salvage in obstetrics has raised some potential concerns. The primary concern involves the theoretic risk of inducing amniotic fluid embolism by transfusing blood contaminated with amniotic fluid. This concern has limited the widespread implementation of cell salvage in obstetrics.

Cell salvage technology appears to effectively remove contaminants from the salvaged blood.^{34,35, 36} Hundreds of reports have been published documenting successful use of intraoperative cell salvage in obstetrics.^37,38 This safety record has prompted The American College of Obstetricians and Gynecologists and others to recommend consideration of this technology for patients at risk for intraoperative hemorrhage.³⁹

Once the operating field is cleared of amniotic fluid, the suction device is changed and blood is collected into the Cell Saver. Fetal blood cells and hemoglobin cannot be reliably removed during the wash process and require Kleihauer-Betke testing and possible Rhogam administration for Rh-negative patients.⁴⁰ In cases of major bleeding, use of cell salvage produces a dilutional coagulopathy by removing clotting factors and platelets from the reinfusion product. The Cell Saver can provide a unit of blood with a hematocrit of 50% in approximately 3 minutes. In patients where blood loss is anticipated to be excessive, more than one Cell Saver may be employed.

Patients at risk for significant intraoperative hemorrhage, as in the setting of invasive placentation, may be candidates for acute normovolemic hemodilution (ANH). Immediately preoperatively, a central line is placed and blood is collected from the patient into special storage bags containing an anticoagulant obtained from the blood bank. At the same time, the patient is given large volumes of crystalloid and/or colloid in a 3:1 ratio, resulting in a dilutional decrease in maternal hematocrit. Blood lost intraoperatively is therefore more dilute. After blood loss is under control (or at the discretion of the surgeon), the patient’s collected blood is reinfused. Collected blood may be stored at room temperature for up to 6 hours.⁴¹ Advantages include preservation of clotting factors and a decreased likelihood of allogeneic transfusion and its associated morbidities.

No adverse fetal effects have been described with this process.^37,42,43 However, patients who might not tolerate an acute decrease in hematocrit are not candidates for ANH, as are those who are already anemic or have coronary artery disease, pulmonary disease, renal or hepatic insufficiency, or evidence of fetal compromise. This technique may be used by some Jehovah’s Witnesses, provided the collection unit remains connected to the central venous line.⁴⁰ There is no role for ANH in the setting of acute hemorrhage. There is paucity of evidence to suggest a decrease in the need for allogenic transfusion after ANH.⁴⁴

Massive transfusion is most commonly defined as the need to administer 10 units of PRBCs in a 24-hour period. This correlates with massive hemorrhage defined as loss of greater than 50% of the patient’s blood volume.⁴⁵ In the nonobstetric literature, mortality rates of 30% to 70% are reported with massive transfusion.⁴⁶ Anticipation and correction of coagulopathy, acidosis, and hypothermia are essential in the management of the massively hemorrhaging patient. Effective resuscitation should include adequate intravenous access, including central and arterial line placement, maintenance of core body temperature above 35°C, utilization of blood warmers, and correction of hypocalcemia and hyperkalemia, in addition to timely administration of crystalloid and component therapy.

Accreditation of Level I Trauma centers by the American College of Surgeons requires the development of a massive transfusion protocol. Key components include a method for rapid communication between the relevant departments in addition to establishing the type and amount of blood products to be delivered and administered. Controversy continues regarding the most appropriate guidelines for massive transfusion, particularly the appropriate ratio of FFP to PRBCs. Emerging data from military combat resuscitations support higher ratios of 1:1. The civilian data are less clear; FFP:PRBCs of 1:1.5 to 1:2 are common. A recent publication demonstrated a mortality reduction in the nonobstetric trauma population following implementation of a massive transfusion protocol. This reduction was attributed to improved communication and more efficient administration of blood products. After protocol implementation, mortality decreased by 58%, and time to first documented transfusion of PRBCs decreased by 39%.⁴⁶ A summary of the protocol utilized in this publication is provided in Fig. 2-1. A higher ratio of PRBC:platelets is also associated with improved survival in several retrospective studies. In a recent study of trauma patients, an FFP:PRBC of 1:2 or higher was associated with an improvement in 30-day survival (59.6% vs 40.4%) compared to lower ratios.⁴⁷ However, these differences in survival using a predefined ratio may be affected by survivor bias.⁴⁸ Most massive transfusion protocols currently aim for a 1:1:1 ratio of plasma:platelets:RBCs.

Despite ongoing debate regarding the ideal ratio of blood replacement products, the implementation of a massive transfusion protocol improves communication and enables a multidisciplinary team approach. After acute bleeding has been controlled and the patient has stabilized hemodynamically, a restrictive approach should be adopted to minimize complications of massive transfusion including acid-base derangements, electrolyte abnormalities, citrate toxicity, and TRALI.⁴⁹ Prospective studies are needed to evaluate the utility of massive transfusion in the obstetric patient. The protocol utilized at our institution is summarized in Table 2-5.

Tranexamic Acid

A large, pragmatic, randomized double-blind, placebo controlled trial is currently underway to quantify the effects of the early administration of tranexamic acid, an antifibrinolytic agent, on death, hysterectomy and other morbidities in women with postpartum hemorrhage. In the World Maternal Antifibrinolytic (WOMAN) trial, 15,000 postpartum women diagnosed with PPH will be eligible for randomization to a single dose of tranexamic acid versus Placebo.⁵⁰ Previous studies evaluating the role of antifibrinolytic agents showed a reduction in delivery-related blood loss^{51,52, 53} but did not provide data on mortality and long-term outcomes. A recent Cochrane analysis of 252 trials showed that prophylactic perioperative use of antifibrinolytics reduces the likelihood of needing allogenic transfusion in surgical patients.⁵⁴

Hemostatic Resuscitation

Hemostatic or “damage control” resuscitation is a new concept utilized in military trauma which aims to (1) avoid crystalloid resuscitation, (2) allow permissive hypotension, and (3) prevent coagulopathy by early aggressive use of blood products.⁵⁵ Permissive hypotension limits blood loss prior to surgical intervention or embolization. Its use is limited in the obstetric setting due to the risk of uterine hypoperfusion in undelivered patients.⁵⁶