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. This chapter is not intended to be an exhaustive reference but will highlight practical concerns and issues for the clinician. We will also discuss some 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), transfusion associated cardiac overload (TACO), acute hemolytic transfusion reactions (AHTR), transfusion-associated sepsis (TAS), and anaphylaxis.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 HIV-1 and HIV-2, human T-lymphotropic virus (HTLV)-I and HTLV-II, hepatitis C virus (HCV), hepatitis B virus (HBV), West Nile virus (WNV), Treponema pallidum (syphilis), Trypanosoma cruzi (Chagas disease), and Zika virus. Cytomegalovirus (CMV) testing is not done on all units, only on enough units to ensure adequate supply of CMV negative blood when needed.

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 CMV, babesiosis, malaria, and Creutzfeldt-Jakob disease. 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 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.

Transfusion-transmitted bacterial infection (TTBI) is more common than HIV and HCV transmission. The risk is highest from pooled platelet transfusion (10.6 per million) versus 0.2 per million red cell units.⁴

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.^5-7

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 76,000 units transfused.⁸ 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.⁹ 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

TRALI is defined as new 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).¹⁰ TRALI complicates at least 1 in 5000 transfusions (0.04%-0.1% of transfused patients) with a 6% risk of mortality and is believed to be the most common cause of mortality related to transfusion.¹¹ 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.¹² 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 three major blood component risk factors for TRALI.¹³ 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.^14,15 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.¹⁰ Patients who develop TRALI can receive additional blood products, but not from the same donor.^16,17

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.¹⁸ 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. Anaphylaxis is relatively rare (1 in 20,000-50,000). 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.¹⁸

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.^2,4,19,20 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.^21-23 A recent Cochrane review of 19 trials involving 6264 patients showed that restrictive transfusion strategies reduced the risk of receiving an 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 (relative risk [RR] 0.77, 95% confidence interval [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.²⁴ 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.²⁵

The American Association of Blood Banks (AABB) proposes the following recommendations for transfusion in the hemodynamically stable patient without active bleeding:

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  Hemoglobin <6 g/dL—Transfusion recommended except in exceptional circumstances.

  
  
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  Hemoglobin 6 to 7 g/dL—Transfusion generally likely to be indicated.

  
  
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  Hemoglobin 7 to 8 g/dL—Transfusion may be appropriate in patients undergoing orthopedic surgery or cardiac surgery, and in those with stable cardiovascular disease, after evaluating the patient’s clinical status.

  
  
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  Hemoglobin 8 to 10 g/dL—Transfusion generally not indicated, but should be considered for some populations (eg, those with symptomatic anemia, ongoing bleeding, acute coronary syndrome with ischemia, and hematology/oncology patients with severe thrombocytopenia who are at risk of bleeding).

  
  
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  Hemoglobin more than 10 g/dL—Transfusion generally not indicated except in exceptional circumstances.²⁶

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).