Transfusion Reactions Workup

Updated: Mar 15, 2023
  • Author: S Gerald Sandler, MD, FCAP, FACP; Chief Editor: Emmanuel C Besa, MD  more...
  • Print

Laboratory Studies

In acute hemolytic reactions, [51] the workup includes the following:

  • Visual inspection of the recipient's plasma and urine
  • Retyping of donor and recipient red blood cells (RBCs)
  • Direct antiglobulin (Coombs) testing

Plasma in a sample of centrifuged anticoagulated venous blood is clear and pink-red if significant intravascular hemolysis (eg, hemoglobinemia) has occurred within the previous few hours. If serum from a nonanticoagulated sample (eg, clotted blood) is examined, a risk exists of traumatic hemolysis in the laboratory when the clot is separated, resulting in a false-positive interpretation. The red discoloration (eg, hemoglobinemia) may be present immediately after transfusion of only several milliliters of incompatible red cells and may persist for hours until the hemoglobin is metabolized to bilirubin. At that time, depending on the volume of incompatible RBCs that were transfused, the plasma may be deep red-brown or yellow.

Within minutes of an ABO blood group–incompatible transfusion, the recipient's urine may become red. To distinguish between hematuria (red cells from the lower urinary tract) and hemoglobinuria (hemoglobin monomers and dimers cleared from the plasma by the kidney), centrifuge the urine. As illustrated below, centrifuged urine from a patient with hematuria is clear yellow with red cells sedimented at the bottom of the tube. Urine from a patient with hemoglobinuria remains clear red and unchanged in color.

Rapid test to distinguish hematuria from hemoglobi Rapid test to distinguish hematuria from hemoglobinuria. The onset of red urine during or shortly after a blood transfusion may represent hemoglobinuria (indicating an acute hemolytic reaction) or hematuria (indicating bleeding in the lower urinary tract). If freshly collected urine from a patient with hematuria is centrifuged, red blood cells settle at the bottom of the tube, leaving a clear yellow urine supernatant. If the red color is due to hemoglobinuria, the urine sample remains clear red after centrifugation.

Repeat ABO typing of the donor's unit should be performed, using a sample from the blood container's segmented tubing. Repeat ABO typing of the recipient is done using a blood sample collected after the transfusion reaction. A discrepancy between the original ABO type and the repeat ABO typings should raise the urgent question of whether a mix-up of blood samples could place another patient at risk of a similar mismatched transfusion.

On direct antiglobulin (Coombs) testing, ABO-related acute transfusion reactions usually cause a positive direct antiglobulin reaction, reflecting the presence of complement (C3d) on circulating red cells, as well as the recipient's anti-A, anti-B, or anti-A,B. In certain situations, donor-derived IgG anti-A, anti-B, or anti-A,B may be detected on circulating red cells.

In febrile nonhemolytic reactions, [60] the recipient's plasma has a normal appearance on visual inspection. Red discoloration indicating hemolysis excludes this diagnosis. The recipient's urine also has a normal appearance. Red discoloration indicating hemolysis excludes this diagnosis. On retyping of donor and recipient red cells for ABO/Rh(D), the results are concordant; no discrepancy should be detected. A direct antiglobulin (Coombs) test yields a negative result.

In allergic reactions, the presence of red plasma or urine, discordant pretransfusion and posttransfusion ABO blood types, or a positive antiglobulin (Coombs) test indicates other diagnoses in addition to an allergic reaction. Allergic transfusion reactions usually do not cause an increased number of eosinophils in subsequent white blood cell (WBC) differential counts.

Anaphylactic reactions are excluded by the presence of red plasma or urine, discordant pretransfusion and posttransfusion ABO blood types, or a positive direct antiglobulin (Coombs) test result. Demonstration of anti-IgA in a pretransfusion sample of the recipient's serum or plasma establishes the diagnosis. Testing for anti-IgA is difficult to perform and is available only in a few reference laboratories; therefore, screening for IgA deficiency should be the initial laboratory study. The presence of IgA in the recipient's pretransfusion sample excludes the diagnosis of a class-specific IgA/anti-IgA reaction.

In transfusion-related acute lung injury (TRALI), [15] plasma levels of brain natriuretic peptide (BNP) may be useful in distinguishing the cardiogenic pulmonary edema present in circulatory overload from the noncardiogenic pulmonary edema present in TRALI. [12] A hemolytic or septic reaction may present with similar symptoms as TRALI and should be excluded. In circulatory overload: Plasma levels of BNP may supplement clinical and radiologic findings.

In bacterial contamination, culture of the implicated unit and the patient's blood is necessary to establish the diagnosis. A hemolytic reaction may present similarly and should be excluded.

In delayed hemolytic transfusion reactions (DHTRs), accelerated hemolysis is indicated by increased serum bilirubin and lactate dehydrogenase concentrations and a decline in total hemoglobin compared with the early post-transfusion value. Mekontso Dessap et al reported that a sharp decline in the hemoglobin A concentration is characteristic of DHTRs, and proposed a diagnostic nomogram for DHTR based on hemoglobin A concentration as a biologic marker of the survival of transfused red blood cells. [61]