Transfusion of Red Cells
Indications For Allogeneic Transfusion
Acute Blood Loss
The decision whether to use red cells depends on the etiology and duration of the anemia, the rate of change of the anemia, and assessment of the patient’s ability to compensate for the diminished capacity to carry oxygen that results from the decrease in red cell mass. Management of acute anemia caused by bleeding or operative blood loss will differ from management of chronic anemia to which the patient has adapted. However, the question underlying any red cell transfusion is whether there is sufficient oxygen delivery to tissues for current needs.
Compensatory mechanisms for acute blood loss include adrenergic response, leading to constriction of venous beds, which improves venous return; increased stroke volume, tachycardia, or both; and increased peripheral resistance, which eventually redistributes blood flow to essential organs. Also contributing to the maintenance of intravascular volume is the shifting of fluid to the intravascular space; this shifting occurs relatively rapidly from the extravascular space and more slowly from the intracellular to the extravascular space.
A decrease in blood volume has distinct effects on oxygen delivery, depending on the volume of blood lost and the functioning of the compensatory cardiovascular responses. Restoration of intravascular volume, usually with crystalloid, ensures adequate perfusion of peripheral tissue and is the first treatment goal for a patient with acute blood loss. Whether red cell transfusion is required depends on the extent of blood loss and the presence of comorbid conditions that may limit host response to the blood loss. The American College of Surgeons has correlated blood loss with clinical findings. Loss of up to 15% of total blood volume (class I hemorrhage) usually has little effect; this amount is the maximum permitted in normal blood donation. A class II hemorrhage (15% to 30% loss) results in tachycardia, decreased pulse pressure, and, possibly, restlessness. A class III hemorrhage (30% to 40% loss) leads to obvious signs of hypovolemia; mental status often remains normal. Red cell transfusion is usually indicated when blood loss exceeds 30% in a patient without other significant comorbid conditions. However, the presence of serious cardiac, peripheral vascular, or pulmonary disease can lower this threshold. For example, anemic patients with significant coronary artery disease are more likely to have serious postoperative myocardial complications.
The threshold for red cell transfusion has been evaluated in two randomized, controlled trials. In one study of transfusion after coronary artery bypass, patients who received transfusions for hemoglobin levels below 8 g/dl did no worse than control patients who received transfusions for hemoglobin levels below 9 g/dl.38 The other trial compared outcomes in critical care patients who received transfusions when their hemoglobin level fell below either 7 g/dl or 10 g/dl.39 Enrollment in this study was limited to patients who were euvolemic at entry and whose hemoglobin levels were from 7 to 9 g/dl; patients who had undergone routine cardiac procedures or who were actively bleeding upon entry to the intensive care unit were excluded. There was no statistical difference in 30-day mortality for these two groups. However, in the subgroups of patients younger than 55 years and patients whose illness was less severe, as defined by standardized clinical criteria, Kaplan-Meier survival estimates were significantly better in the patients who were not transfused unless hemoglobin levels dropped below 7 g/dl. These results are provocative, but they must be interpreted cautiously. They do suggest that more restrictive transfusion policies may be safely adopted for selected patients. However, the enrollment criteria may have biased the findings, and this calls into question the applicability of these findings to other settings.
Table 4 Indications for Platelet Transfusion
|
Platelet Count (yl) |
Indication for Transfusion |
|
< 10,000 |
All patients, even if asymptomatic |
|
< 20,000 |
Coagulation disorder or minor bleeding |
|
< 50,000-100,000 |
Major bleeding or surgical procedure |
Chronic Anemia
In the chronically anemic patient, an increase in red cell 2,3-diphosphoglycerate leads to a shift in the oxygen dissociation curve and improved delivery of oxygen to tissues. This adaptation augments the mechanisms for improved oxygen delivery described above. Indications for transfusion depend on clinical assessment of the adequacy of oxygen delivery and are also guided by the etiology of the anemia. If the anemia can be reversed with iron, folic acid, or vitamin B12, transfusion therapy is indicated only in patients with clinical findings that cannot be tolerated while endogenous red cell mass is being regenerated. Patients with chronic renal disease are typically deficient in ery-thropoietin. Replacement therapy with exogenous erythropoi-etin [see 5:III Anemia: Production Defects] often obviates transfusion. Patients with anemia that is a result of chronic disease such as rheumatoid arthritis, malignancy, or AIDS may also respond to erythropoietin.40,41
Relatively little is known about transfusion thresholds in specific medical illnesses. An observational trial has addressed the effect of anemia on the 30-day mortality of elderly patients hospitalized with acute myocardial infarction. Mortality was reduced in those patients who were transfused to a hematocrit of 30% to 33%, but transfusion had little or no effect on patients who presented with a hematocrit already in the 30% to 33% range.42
Indications For Autologous Transfusion
Whether the criteria for autologous transfusion should be the same as that for allogeneic transfusion remains unresolved. Although the risk associated with autologous blood is less than that associated with allogeneic blood, it is not zero. Errors in labeling, storage, and processing can still occur. For these reasons, many argue that uniform standards based on oxygen delivery should apply, regardless of the blood source. Others, citing the reduced risk, advocate returning most or all of the predeposited units to the patient. There is no clinical evidence that either transfusion policy is associated with better or worse patient outcomes.43
Intraoperative and postoperative blood salvage can also help limit allogeneic blood use. Blood salvage is employed in procedures associated with the shedding of large volumes of blood; it involves returning concentrated red cells to the patient after those cells have been washed. Preoperative isovolemic hemodi-lution (PIH) is a process in which blood collected immediately before surgery is returned as needed postoperatively. This strategy has been shown to be a cost-effective alternative to preoper-ative autologous donation in patients undergoing radical prostatectomy.44 PIH would be particularly useful if an oxygen-carrying blood substitute were available to replace the autologous blood that is removed. Until it is clear that the cardiovascular risks associated with acute hemodilution do not outweigh the risks associated with allogeneic blood, this approach should be considered with caution.
Transfusion of Platelets
In general, the decision to transfuse platelets rests on the answers to two questions: (1) Is the thrombocytopenia the result of underproduction or increased consumption of platelets? and (2) Do the existing platelets function normally?
Indications For Transfusion
Low Platelet Count
Thrombocytopenia can result from decreased production caused by marrow hypoplasia or from increased consumption caused by conditions such as idiopathic thrombocytopenic pur-pura (ITP). In a patient with ITP, surviving platelets are larger and younger and function better than would be expected given the platelet count; platelet transfusion is largely avoided or minimized for such a patient. In contrast, with hypoplasia, platelet function is more severely impaired, and the risk of bleeding is relatively higher. Thus, the decision to transfuse patients who have hypoproliferative thrombocytopenia is generally based on their platelet count and is initiated prophylactically when the count drops below a certain threshold. Published consensus guidelines provide an excellent summary of all aspects of platelet therapy.45
Studies have shown that the prevalence of bleeding increases significantly below a threshold of about 10,000 platelets/^l in otherwise asymptomatic patients.46 The desire to avoid allogene-ic donor exposure, cost concerns, and increasing platelet demand have encouraged the use of transfusion policies similar to the policy proposed by Wandt and colleagues [see Table 4].45,46
Nonfunctioning Platelets
Platelet function is the second criterion for the transfusion of platelets. Transfusion is appropriate in a bleeding patient whose platelet count is adequate but whose platelets are nonfunctional as a result of medications such as aspirin or nonsteroidal anti-inflammatory drugs or as a result of bypass surgery. In a bleeding patient, if platelet dysfunction is from inherited or acquired defects, transfusion is indicated to provide a minimum number of normal platelets. Platelet function is abnormal in uremic patients, and definitive treatment requires correction of the uremia. Some studies suggest that interventions that increase von Wille-brand factor levels, such as desmopressin (1-desamino-8-D-argi-nine vasopressin [DDAVP]) conjugated estrogen, or cryoprecip-itate, may favorably influence platelet function in uremia.47 In vitro evidence suggests that DDAVP may improve platelet dysfunction caused by glycoprotein IIb/IIIa (GPIIb/IIIa) inhibitors (e.g., eptifibatide, abciximab, tirofiban) or aspirin.
Contraindications to Platelet Transfusion
Proper investigation of the causes of thrombocytopenia will identify clinical situations in which platelets should be withheld because they contribute to evolution of the illness. These disorders include thrombotic microangiopathies such as TTP, he-molytic-uremic syndrome, and HELLP syndrome (hemolysis, elevated liver enzymes, and a low platelet count). Posttransfusion purpura is usually unresponsive to platelet transfusion but may respond to plasma exchange or intravenous immunoglobu-lin (IVIg). Platelet transfusions will not help patients with autoimmune thrombocytopenia (e.g., ITP), but they also will not harm them.
Response to Platelet Transfusions
Both platelet and host factors influence the response to platelet transfusions. Length of in vitro storage, storage temperature, adequacy of oxygenation, and extent of pretransfusion manipulation all influence in vivo survival. Important host factors that influence survival are temperature, splenomegaly, ABO compatibility, and immune status.
A transfusion of appropriately stored fresh platelets— whether pooled concentrates or SDPs—should contain about 6,000/^l to 10,000/m-1 platelets per unit (5.5 x 310 platelets). Thus, in an unsensitized 75 kg (165 lb) recipient, each unit should yield an increment of about 60,000 platelets/^1. When needed, a post-transfusion count is usually obtained after 1 hour but can be obtained as early as 10 minutes after transfusion. A patient is considered refractory to platelet transfusions when the 1-hour posttransfusion increment is less than 10,000 platelets/after the patient is given 3.3 x 1011 platelets.
Platelet Transfusions in Refractory Cases
Platelets have platelet-specific antigens, human leukocyte antigens (HLA), and blood group antigens. Immune response to any of these can contribute to platelet unresponsiveness. Platelet surfaces have only class I HLA antigens, of which only HLA-A and HLA-B are clinically important. Polymorphic antigens are found in association with each of the major platelet proteins: HPA1a/2a (formerly called P1A1/A2) and Pen on glycoprotein IIIa, Bak system on glycoprotein IIb, and Br and Ko on glycoproteins Ia and Ib. Each of these antigen groups is associated with isoim-mune neonatal thrombocytopenia. The prevalence of antibodies to platelet-specific antigens is increased for patients sensitized to HLA antibodies; therefore, antibodies to both sets of epitopes may contribute to refractoriness in patients who fail to respond to HLA-matched platelets.
Treating a patient refractory to platelet transfusions involves addressing nonimmune causes (e.g., fever, sepsis, bleeding, and disseminated intravascular coagulation [DIC]) and providing recently collected ABO-compatible products. If these strategies fail, minimization of the effects of HLA antibodies or platelet antigens through HLA typing, platelet crossmatching, or both is in-dicated.50 Selecting platelets matched at the HLA-A and HLA-B loci may improve responsiveness in about half of patients with positive HLA antibody screens. Unless contraindicated because of transplant considerations, an empirical trial of donations from family members may also be helpful.
In one study undertaken to determine the best method of treating refractory cases, platelet selection by crossmatching was compared with selection by HLA criteria. Selection by cross-matching was equivalent to HLA selection and yielded better re-suits.51 Another study found that crossmatched platelets provided equivalent platelet increments that were independent of the grade of HLA match.52 Although these results are promising, the effectiveness of selection either by HLA and crossmatching or by crossmatching alone is often limited by nonimmune host factors. Additionally, these techniques are not yet routinely available.
Modifying the effects of alloimmunization is difficult. IVIg can improve platelet increments but not platelet survival. An analysis of IVIg therapy found that about 50% of alloimmunized patients appeared to benefit from such therapy.50 Plasma exchange is of limited value because it is difficult to remove IgG antibodies. In some patients, the HLA antibodies responsible for refractoriness may regress over time, so it is important to periodically retest for them. If the HLA antibody screen becomes negative, a trial of non-HLA-matched platelets is warranted.
All in all, the best strategy is prevention, which can be achieved by avoiding unnecessary transfusions and using only leukocyte-depleted products. A randomized, prospective trial of how best to prevent alloimmunization of newly diagnosed patients with acute myeloid leukemia showed equivalent rates of alloimmunization and platelet refractoriness for filtered platelet concentrates, filtered SDPs, and ultraviolet B-irradiated plate-lets.53 However, leukocyte reduction did not prevent secondary immune responses in patients already sensitized through either pregnancy or transfusion.
Transfusion of Fresh Frozen Plasma, Plasma Derivatives, and Recombinant Products
Fresh Frozen Plasma
Despite a paucity of indications for FFP use, roughly two million units are transfused annually55 [see Table 3]. FFP is most appropriate for replacing the multiple coagulation deficiencies that result from massive transfusion, liver disease, warfarin toxicity, or acute or chronic DIC. In addition, it can be used to treat throm-botic microangiopathies and specific factor deficiencies when factor concentrates are not available. After one blood volume exchange using only red cells, plasma components are diluted to about 40% of their original concentration; after two blood volume exchanges, plasma components are diluted to 15%. Prothrombin time (PT) and partial thromboplastin time (PTT) become prolonged when coagulation components are lower than 30%, but abnormal bleeding from dilution usually does not occur until these values are less than 17% of normal. Microvascular bleeding associated with a PT and PTT greater than 1.5 times normal is an indication for FFP.56 Whether FFP replacement is needed when PT and PTT are over 1.5 times normal but not associated with bleeding is less clear-cut; paracentesis and thoracentesis did not cause increased bleeding in patients with PT and PTT that were up to twice normal values.
The FFP dose depends on whether or not a consumptive process is being treated in addition to hemodilution. For hemo-dilution, 15 ml/kg will usually be sufficient. However, if consumption is occurring, the dose is best guided by the effect of treatment on PT and PTT. If fibrinogen is lower than 80 mg/dl, cryoprecipitate may be required to rapidly increase fibrinogen. However, four units of FFP can be used in most cases to provide the same amount of fibrinogen as one pool of cryoprecipitate. Urgent reversal of the effects of warfarin can usually be accomplished with about 5 to 10 ml/kg of FFP.
Factor XI concentrates, which still have some thrombogenic potential, are available but not yet licensed in the United States.58 Therefore, FFP is the treatment for factor XI deficiency. FFP is not used to replace antithrombin III, because a purified concentrate is available.
Thrombotic microangiopathies [see 5:XIII Hemorrhagic Disorders] are treated with either FFP transfusions or, more often, plasma exchange with either FFP or cryopoor plasma.60Studies suggest that cryopoor plasma may be an alternative to FFP in the treatment of TTP.61 The dose of either product is usually equal to a plasma volume exchange of 1.0 to 1.5, which is carried out daily until clinical improvement occurs.
Factor VII A
Recombinant activated factor VII was approved in 1999 for the treatment of bleeding episodes in patients with hemophilia A or B who have antibodies (inhibitors) to factor VIII or IX, respectively. Factor VIIa is also the treatment of choice for the rare patient with factor VII deficiency, whether acquired—as, for example, a consequence of liver disease—or inherited. It is not approved for this purpose, however. In addition, factor VIIa is useful in activation of the coagulation tissue factor pathway. For patients with inhibitors, factor VIIa is given at a dosage of 90 Mg/kg as a slow I.V. push over 2 to 5 minutes; the dosage is repeated every 2 hours, as needed. For factor VII deficiency, the dosage is 20 to 30 Mg/kg given as a slow I.V. push over 10 minutes; given in this manner, factor VIIa treatment will reduce the PT to normal within 20 minutes after administration. Depending on the clinical setting, the PT will become prolonged again 3 to 4 hours after treatment.
Off-label use of this product to treat uncontrolled hemorrhage in patients who do not have a preexisting bleeding disorder and who are unresponsive to FFP is becoming more common.62 However, it is important not to use factor VIIa in patients with DIC, because VIIa may exacerbate the DIC. The high cost of this product and its potential for contributing to DIC should limit its use to carefully selected patients for whom other alternatives are not available.
Factor VIII Concentrates
The introduction of plasma-derived factor VIII concentrates in the 1960s brought a significant improvement in the treatment of hemophilia A. Unfortunately, these concentrates were derived from large donor pools, and contamination of the factor with HBV, HVC, and, especially, HIV resulted in the widespread transmission of these infections in the hemophilia community. Since 1980, new methods of heat sterilization, solvent/detergent treatment, and immunoaffinity purification have yielded an array of factor concentrates that are highly purified and unable to transmit these infections. The efficacy of these viral-inactivation methods has been validated by using reverse transcription and PCR studies to measure HCV RNA in factor VIII concentrates; HCV RNA was present in 100% of products before treatment but was undetectable after treatment. Besides reducing the risk of infection, use of high-purity factor VIII concentrates may be associated with better preservation of patients’ cell-mediated immunity. The 1980s also saw the advent of recombinant factor VIII concentrates.
The factor VIII preparation Humate-P is also rich in von Willebrand factor and is approved for the treatment of von Willebrand disease. This product has the major advantage of being free of the risks of infection associated with cryoprecipitate. If Humate-P is not available, the factor VIII preparations Al-phanate or Koate-DVI may be used, but they are not approved for this purpose and their efficacy is uncertain.
The advances in safety and purity of factor VIII concentrates, especially in the case of the recombinant products, have increased the cost per unit fivefold to 10-fold. Recombinant products are used primarily for newly diagnosed patients with hemophilia who have not been exposed to plasma products. Work is just beginning on modifying these recombinant products to make them more effective by reducing immunogenicity and prolonging circulation time.63
The possibility that a nonhuman source of factor VIII would be useful in the treatment of patients with acquired factor VIII inhibitors led to the development of a highly purified porcine factor VIII concentrate. This was shown to be effective for patients whose anti-factor VIII antibody does not cross-react with the porcine product.64 About one third of patients develop antibodies to the porcine product, which limits its usefulness for repeat treatments.
Factor IX Concentrates
Factor IX complex concentrates contain about equal amounts of the vitamin K-dependent factors II, VII, IX, and X. These preparations are available in several degrees of purity, but all have the disadvantage of being thrombogenic when used for extended periods or in patients with liver disease. Highly purified factor IX, prepared by immunoaffinity chro-matography, is free of this complication and is the product of choice in treating factor IX deficiency.65 Activated prothrom-bin complex concentrates (Autoplex-T and FEIBA) have been used to bypass the need for factor VIII in selected patients with hemophilia A and acquired inhibitors. This provides an alternative for patients who do not respond to porcine factor VIII [see 5:XIII Hemorrhagic Disorders].
Transfusion of Granulocytes
Studies have shown granulocyte transfusion to be effective in the treatment of neutropenic patients. Transfusion of granulo-cytes in doses in the range of 8.3 x 1010 can be obtained by apheresis of donors who have been pretreated with granulocyte colony-stimulating factor (G-CSF) and a single dose of dexa-methasone. Granulocyte transfusions at these dose levels have been shown to produce measurable, sustained increments in neutrophils, even into the normal range. The indications and clinical benefits of granulocyte transfusion at these higher doses are still being determined. Randomized trials are required to fully define the clinical efficacy of granulocyte transfusions. After collection, granulocytes must be stored at room temperature and irradiated to prevent transfusion-associated graft versus host disease. Crossmatching should be done to ensure compatibility.66
Transfusion of Immune Globulin
Many human immune globulin preparations are available. Immune serum globulin, administered intramuscularly, is used to treat chronic immunodeficiency disease and for prevention or alleviation of measles. Hepatitis A can now be prevented by vaccination [see 4:VII Acute Viral Hepatitis]. Alternatively, a traveler who will spend less than 3 months in an endemic area can receive 0.02 ml/kg of immune serum globulin. Hepatitis B immune globulin is used for postexposure prophylaxis against HBV infection [see CE:V Adult Preventive Health Care]. It is prepared from plasma with high titers of antibody to hepatitis B surface antigen. Rho(D) immune globulin is used to prevent the development of anti-Rho (anti-D) antibodies in Rh-negative women who have just given birth, undergone amniocentesis, or aborted, if the biologic father is thought to be Rh positive.
Intravenous administration of human immune globulin promptly elevates circulating IgG levels and is preferable to intramuscular administration. Several preparations of IVIg are available to treat chronic immunodeficiency disease67 [see 6:VIII Deficiencies in Immunoglobulins and Cell-Mediated Immunity]. The intravenous dosage for such deficiency syndromes is 0.2 g/kg/mo but can be raised to 0.3 g/kg/mo or the agent can be given more often if needed.
The most common side effects of IVIg therapy—headache, nausea, and fever—usually respond to symptomatic treatment and reduction of the infusion rate. Rarer and potentially more severe side effects are anaphylactic reactions, hemolysis from anti-A and anti-B antibodies, and acute renal failure. Renal failure has been attributed to osmotic nephrosis caused by the high sucrose concentration in many IgG preparations.68,69 In one study, aseptic meningitis was the most common of the serious side effects, with a frequency of 11% (95% confidence interval, 4% to 23%); patients with a history of migraine had a significantly higher incidence of aseptic meningitis.70Aseptic meningitis usually occurs within 24 hours after administration and does not respond to a reduction of the infusion rate. Patients may be required to stay in the hospital for symptomatic treatment; if further treatment is needed, changing the lot or preparation of IVIg may alleviate this side effect. Current manufacturing practices eliminate HCV from IVIg preparations.
Transfusion of Stem Cells
Stem cell transplantation, initially pioneered for use in leukemia, is used to treat a number of life-threatening, malignant, hereditary, and immunologic disorders [see 12:XV Chronic Lymphoid Leukemias and Plasma Cell Disorders].
Complications of Transfusions
Hemolytic Transfusion Reactions
Hemolytic transfusion reactions are classified as immediate or delayed, depending on their pathophysiology. Immediate he-molytic reactions are the result of a preexisting antibody in the recipient that was not detected during pretransfusion testing. Delayed hemolytic reactions are the result of an anamnestic response to an antigen to which the recipient is already sensitized. The renewed antigenic stimulation in a person already primed by previous antigenic exposure results in recrudescence of antibody to levels that can cause hemolysis. This is in contrast to an immune response during primary sensitization, which seldom causes hemolysis, because antibody levels develop at a much slower rate.
Patients with sickle cell disease are more likely than others to become alloimmunized and to have delayed hemolytic transfusion reactions, which often occur in association with recrudescence of an occlusive pain crisis. These reactions are occasionally associated with severe hemolysis involving autologous, as well as allo-geneic, red cells. The cause of these episodes is unknown but has been attributed to so-called bystander hemolysis associated with abnormal function of CD59 (MIRL, membrane inhibitor of reactive lysis), transfusion-associated marrow suppression, or both.71
Diagnosis of Hemolytic Reactions
The pathophysiologic differences between immediate and delayed hemolytic transfusion reactions account for some of their differences in clinical findings. Fever is a common sign associated with both immediate and delayed hemolytic transfusion reactions.
Clinical evidence of hemolysis is likely to be more severe in immediate hemolytic reactions and may include back pain, pain along the vein into which the blood is being transfused, changes in vital signs, evidence of acute renal failure, and signs of developing DIC. These findings are probably caused by immune complexes activating the complement and kinin systems, by the direct effects of red cell stroma on kidney function, and possibly by the release of inflammatory cytokines such as interleukin-1| (IL-1|), IL-6, and tumor necrosis factor (TNF).72
In delayed hemolytic reactions, hemolysis with hemoglobine-mia and hematuria (sometimes associated with renal failure) also occurs, but it is less common and generally less severe. In many delayed hemolytic transfusion reactions, the only clinical findings may be a newly positive Coombs test result, the appearance of a new antibody against red cell antigens that are not present on the recipient’s red cells, or both. When hemolysis is absent, these reactions are sometimes called delayed serologic transfusion reactions. At the Mayo Clinic, two surveys sought to identify the relative incidence of both kinds of delayed transfusion reactions. The most recent survey, covering the period from 1993 to 1998, revealed a relative increase in delayed serologic transfusion reactions and an associated decrease in delayed he-molytic reactions, with overall increases in the incidence of these reactions. The earlier survey, which covered the period from 1980 to 1992, revealed an association between delayed transfusion reactions and the presence of antibodies to Jka and Fya or antibodies with multiple specificity; this association was not found in the later survey. These changes probably result from improved systems for identifying clinically significant non-hemolytic antibodies.73
In some cases, antiglobulin testing may yield positive results after all the transfused cells have been cleared, often with only complement being detected on the red cells. This finding has been attributed to autoimmune hemolysis after the delayed transfusion reaction.
Treatment of Hemolytic Reactions
As soon as a hemolytic transfusion reaction is suspected, the transfusion should be immediately discontinued. The diagnosis can be confirmed or excluded by sending the remaining blood product, together with a freshly drawn posttransfusion specimen, to the blood bank. The blood bank rechecks all records, confirms the patient’s type and antibody screen, checks for evidence of hemoglobin in the plasma, and rechecks the crossmatch and antiglobulin test results. These tests will confirm or disprove the diagnosis and identify the antibody causing the immediate hemolytic reaction, when present. Until these studies have been completed, any further blood products can be given only with the approval of the blood bank’s medical director.
The side effects of an acute hemolytic transfusion reaction can be managed by supporting renal blood flow with furosemide and supporting tubular urine flow with mannitol; treating shock, if required, with pressors; and giving platelets and FFP as needed to control coagulopathy if DIC develops. Intravenous steroids may be useful. Until the antibody causing the immune hemolysis is identified, only type O red cells and AB plasma should be used.
Managing delayed transfusion reactions is simpler because of the slower tempo at which these reactions develop. The diagnosis requires identifying a new antibody against red cell antigens and searching for clinical evidence of hemolysis. Treatment requires replacement with the appropriate antigen-negative blood products. Acute renal failure and DIC are unlikely but would be managed as described for immediate hemolytic reactions. The severe, atypical delayed transfusion reactions sometimes found in patients with sickle cell disease may require steroids and transfusion support.
Prevention of Hemolytic Reactions
Prevention of immediate and delayed hemolytic transfusion reactions depends on recognizing their respective proximate causes. Immediate hemolytic reactions are usually caused by technical errors made during the procurement or processing of blood specimens, during pretransfusion testing, or during product infusion. In a review of transfusion-related deaths reported to the Food and Drug Administration between 1990 and 1998, approximately 50% were caused by clerical errors that led to transfusion of ABO-incompatible blood, a rate virtually unchanged since reporting began in 1976.74 Prevention of immediate transfusion reactions is best accomplished by following protocols for obtaining specimens from patients in adequate time before transfusion and checking to see that blood products are appropriate for the intended recipient.
Delayed transfusion reactions are the result of an anamnestic response of antibodies from a previous transfusion (or pregnancy) that are not present in detectable levels at the time the specimen is crossmatched. A careful transfusion history can best prevent delayed hemolytic reactions. Many patients will know whether there were difficulties involving blood obtained for transfusion. If a patient has a history of difficulty with cross-matches, the blood bank can obtain the details from the institution responsible for the previous transfusion. A proper transfusion history can uncover patients likely to have antibodies that the blood bank would not detect. For example, antibodies to Jka and Fya are characteristically hard to identify because they are quick to rise on stimulation and fall equally rapidly, making later detection difficult.
