Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (643 page)

Acute HTR can be life threatening and classically present with fever, flank pain, red/dark urine, pain at infusion site, nausea/vomiting, diarrhea, hypotension, and a feeling of impending doom. The severity of the reaction in these cases is often related to the dose of incompatible RBCs transfused. Thus, whenever a transfusion reaction is suspected, the transfusion should be terminated immediately and a posttransfusion specimen should be sent to the blood bank for workup. If the patient appears to be having a severe HTR, the patient will need supportive care, possibly in an ICU setting. In order to prevent acute tubular necrosis, it is critical to maintain renal blood flow and urinary flow by administering intravenous fluids and diuretics. Additionally, intravenous immunoglobulin (IVIG) may be of benefit in some patients.

In many instances, if the hemolysis is due to a non-ABO blood group antibody, the patient will present with a delayed HTR, which is characterized by a drop in hematocrit, a rise in bilirubin, and the presence of a previously undetected antibody. These patients may be completely asymptomatic or may present with jaundice, dark urine, and/or symptoms of anemia. It is important to note that in addition to any acute management, the serologic workup of the patient is critical as the patient will likely require subsequent transfusion. If the incompatibility is not discovered, the patient may have another HTR that may be more severe than the previous.

TRANSFUSION-RELATED ACUTE LUNG INJURY (TRALI)

TRALI is one of the leading causes of mortality related to blood product transfusion and is caused by activation of the recipient’s neutrophils in the pulmonary vasculature. This results in increased vascular permeability in the pulmonary capillaries and extravasation of serum into the alveolar spaces. The neutrophils of the recipient are activated by HLA antibodies, antineutrophil antibodies, or lipid activators in the blood product transfused.

   Who Should Be Suspected?

The classic presentation of TRALI is a patient who develops acute respiratory distress either during or within 6 hours of transfusion of a blood product that contains plasma. Patients may also have fever, chills, hypotension, and diffuse bilateral lung infiltrates on chest radiography. The treatment for TRALI is mainly providing supportive care that may include oxygenation and possibly ventilatory support. Although corticosteroids have been used in patients with TRALI, it is not clear if there is any benefit to their use. As TRALI is caused by the blood products donated by a particular donor, the patient can be transfused with additional blood products if necessary. However, the donor implicated in the reaction should be removed from the donor pool.

TRANSFUSION-ASSOCIATED CIRCULATORY OVERLOAD (TACO)

   Who Should Be Suspected?

In clinical practice, it is often difficult to differentiate TRALI from TACO. Some features that differ between TACO and TRALI include (1) hypertension in TACO (vs. hypotension in TRALI), (2) fever is not seen in TACO, (3) the B-type natriuretic peptide is significantly elevated in TACO, and (4) brisk response to diuresis may be seen in TACO. A history of cardiac dysfunction or excessive/rapid volume infusion also suggests TACO as the likely etiology of the reaction.

MANIPULATION OF BLOOD PRODUCTS

Blood component therapy is significantly safer and superior to the transfusion of whole blood as a patient is transfused with only the blood component that is necessary. Additional blood product manipulation (other than component separation) may also be necessary for a small minority of patients. Some of the possible manipulations include leukoreduction, irradiation, and washing of blood components.

Leukoreduction is usually performed during component preparation by filtration. Some of the benefits of leukoreduction include a reduced risk of febrile transfusion reactions, immunomodulation, CMV transmission, and HLA immunization. Previously, leukoreduction was performed only for a select group of patients (e.g., oncology patients, other chronically transfused patients). However, due to the multiple benefits of leukoreduction and increased availability of prestorage filtration, many institutions now provide leukoreduced blood products for all patients.

Irradiation of blood products is performed to reduce the risk of transfusionassociated graft versus host disease (TA-GVHD) in patients susceptible to this almost uniformly fatal condition. TA-GVHD occurs due to engraftment of viable lymphocytes that are transfused with a cellular blood product resulting in an immune response against the recipient’s tissues. This condition is similar to conventional GVHD with one important exception. Unlike patients with conventional GVHD, patients with TA-GVHD also have destruction of the hematopoietic cells in the patient’s bone marrow. This results in irreversible pancytopenia and patients usually succumb to infection or bleeding.

   Considerations

Gamma irradiation of cellular blood products prevents TA-GVHD. The indications for transfusion of irradiated blood products include (but is not limited to) (1) hematologic malignancies and some solid neoplasms, (2) hematopoietic progenitor cell transplantation, (3) intrauterine transfusions, (4) premature/low birth weight infants, (5) newborns with erythroblastosis, (6) congenital immunodeficiencies, (7) treatment with purine analogues and related drugs, (8) treatment with alemtuzumab and related drugs, (9) granulocyte transfusions, and (10) transfusion from a genetically similar donor (includes family members/relatives, HLA-selected donors, genetically homogeneous populations). Irradiation of blood products is not necessary for patients with HIV infection. Please see the suggested reading for a more comprehensive discussion of TA-GVHD and irradiation of blood products.

Washing of RBCs and platelets is occasionally necessary in patients who have severe or recurrent allergic transfusion reactions. The allergen causing the reaction is usually a protein that is present in the donor’s plasma. Plasma is present in packed RBC as well as whole blood–derived and apheresis platelets, and washing these products using saline in a device designed to do so will remove almost all of the plasma in the product. Since washing the blood component will result in loss of some of the red cells and platelets in the product, washing should only be performed for patients who require it.

PERINATAL TRANSFUSION PRACTICE

HEMOLYTIC DISEASE OF THE FETUS AND NEWBORN (HDFN)

HDFN is caused by maternal alloantibodies to fetal red cell antigens and is an important cause of fetal morbidity and mortality. If untreated, HDFN can result in fetal anemia, high-output cardiac failure, and hydrops fetalis. The TM service plays an important role in the diagnosis and treatment of HDFN.

   Who Should Be Suspected?

Currently in the United States, HDFN is seen most commonly in group O women who have a non–group O fetus. Although common, the HDFN seen in these patients is usually mild. However, if an Rh-negative mother has anti-D and the fetus is D positive, this fetus is at a very high risk of HDFN. Due to the use of Rh immune globulin (RhIg), a commercially available antibody to the D antigen, the prevalence of HDFN has substantially decreased in developed countries. Other commonly implicated antibodies in HDFN include K, c, C, and Fy
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In order to prevent or initiate early treatment of HDFN, all pregnant patients should have a type and screen performed at their first prenatal visit, and their medical history should be reviewed for any previous transfusion or alloimmunization due to pregnancy or transfusion. The alloantibodies implicated in HDFN are usually IgG antibodies that cross the placenta and result in hemolysis and anemia of the fetus.

If the patient has any clinically significant antibodies, titers of the antibody should be performed and repeated monthly. If the titer rises to 16 or higher (may vary by institution) with AHG, there is a significant risk of HDFN, and the risk to the fetus can be further assessed by determining whether the cognate antigen is present on the red cells of the fetus. The phenotype of the fetus can be determined by checking the father’s red cell phenotype and/or by amniocentesis/cordocentesis. If necessary, the patient should be referred to an experienced high-risk obstetrician who will closely follow the pregnancy and assess the fetus for anemia using color Doppler ultrasound of the middle cerebral artery blood flow. If the fetus is significantly anemic, intrauterine transfusion of the fetus can be considered. After delivery of a fetus at risk of HDFN, the cord blood should be evaluated. If the neonate has a positive DAT and significant hemolysis resulting in anemia and/ or hyperbilirubinemia, an exchange transfusion of the neonate must be considered. For transfusing the neonate (as well as intrauterine transfusion if necessary), group O, Rh-negative, irradiated red cells that are crossmatch compatible with the mother are generally preferred.