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 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]

Treatment & Management

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Media Gallery

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.

of 1

Author

S Gerald Sandler, MD, FCAP, FACP Professor Emeritus of Medicine and Pathology, Georgetown University School of Medicine

S Gerald Sandler, MD, FCAP, FACP is a member of the following medical societies: American Association of Blood Banks, College of American Pathologists, International Society of Blood Transfusion

Disclosure: Nothing to disclose.

Coauthor(s)

Viviana V Johnson, MD Medical Director, Blood Bank, Naval Medical Center, Portsmouth

Viviana V Johnson, MD is a member of the following medical societies: American Association of Blood Banks, College of American Pathologists

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Ronald A Sacher, MD, FRCPC, DTM&H Professor Emeritus of Internal Medicine and Hematology/Oncology, Emeritus Director, Hoxworth Blood Center, University of Cincinnati Academic Health Center

Ronald A Sacher, MD, FRCPC, DTM&H is a member of the following medical societies: American Association for the Advancement of Science, American Association of Blood Banks, American Clinical and Climatological Association, American Society for Clinical Pathology, American Society of Hematology, College of American Pathologists, International Society of Blood Transfusion, International Society on Thrombosis and Haemostasis, Royal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

Chief Editor

Emmanuel C Besa, MD Professor Emeritus, Department of Medicine, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American Society of Clinical Oncology, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, New York Academy of Sciences

Disclosure: Nothing to disclose.

Additional Contributors

Pradyumna D Phatak, MBBS, MD Chair, Division of Hematology and Medical Oncology, Rochester General Hospital; Clinical Professor of Oncology, Roswell Park Cancer Institute

Pradyumna D Phatak, MBBS, MD is a member of the following medical societies: American Society of Hematology

Disclosure: Received honoraria from Novartis for speaking and teaching.

Acknowledgements

The views expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, nor the U.S. Government.

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