eMedicine Specialties > Hematology > Transfusion Medicine

Transfusion Reactions: Differential Diagnoses & Workup

Author: S Gerald Sandler, MD, FACP, FCAP, Professor of Medicine and Pathology; Director, Transfusion Medicine, Department of Laboratory Medicine, Georgetown University Hospital
Coauthor(s): Viviana V Johnson, MD, FCAP, Medical Director, Transfusion Services and Armed Services Blood Bank Center, National Naval Medical Center
Contributor Information and Disclosures

Updated: Oct 4, 2009

Differential Diagnoses

Anaphylaxis
Septic Shock
Angioedema
Shock, Hemorrhagic
Disseminated Intravascular Coagulation
Sudden Cardiac Death
Food Allergies
Urticaria
Hemolytic Anemia
Hypersensitivity Reactions, Immediate
Pulmonary Edema, Cardiogenic

Other Problems to Be Considered

Cold agglutinin immune hemolysis

Workup

Laboratory Studies

  • Acute hemolytic reactions36
    • Visual inspection of the recipient's plasma: 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.
    • Visual inspection of the recipient's urine: 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 and in Image 1, 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 hemoglob...

      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.

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      Rapid test to distinguish hematuria from hemoglob...

      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.

    • Retyped donor and recipient RBCs: Repeat ABO typing of the donor's unit using a sample from the blood container's segmented tubing. Repeat ABO typing of the recipient 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.
    • Direct antiglobulin (Coombs) test: 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.
  • Febrile nonhemolytic reactions46
    • Visual inspection of the recipient's plasma: The appearance is normal. Red discoloration indicating hemolysis excludes this diagnosis.
    • Visual inspection of the recipient's urine: The appearance is normal. Red discoloration indicating hemolysis excludes this diagnosis.
    • Retype 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.
  • 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
    • The presence of red plasma or urine, discordant pretransfusion and posttransfusion ABO blood types, or a positive direct antiglobulin (Coombs) test excludes this diagnosis.
    • 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.
  • TRALI8
    • Plasma levels or 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.5
    • A hemolytic or septic reaction may present with similar symptoms and should be excluded.
  • Circulatory overload: Plasma levels of BNP may supplement clinical and radiologic findings.
  • 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.

More on Transfusion Reactions

Overview: Transfusion Reactions
Differential Diagnoses & Workup: Transfusion Reactions
Treatment & Medication: Transfusion Reactions
Follow-up: Transfusion Reactions
Multimedia: Transfusion Reactions
References
Further Reading
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References

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Further Reading

Additional Resources

  • Brecher ME, ed. Technical Manual. 15th ed. Bethesda, Md: American Association of Blood Banks Press; 2005.
  • Hillyer CD, Silberstein LE, Ness PM, Anderson KC, Roback JD, eds. Blood Banking and Transfusion Medicine. 2nd ed. Philadelphia, Pa: Churchill Livingstone; 2007.
  • Hillyer C, Strauss RG, Luban NLC, eds.   Handbook of Pediatric Transfusion Medicine. San Diego, Calif: Elsevier Academic Press; 2004.
  • Petz LD, Garratty G, eds. Immune Hemolytic Anemias. 2nd ed. Philadelphia, Pa: Churchill Livingstone, 2004.

Related eMedicine Topics

Clinical Trials

Clinical Guidelines

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Keywords

transfusion reactions, blood transfusions, blood products, hemolytic transfusion, acute hemolytic transfusion reactions, transfusion complications, transfusion syndrome, blood product reactions, allergic transfusion reaction, blood type, blood group incompatibility, circulatory volume overload, anaphylactic transfusion reaction, blood anaphylaxis, hemolytic reactions, allergic reactions, anaphylactic reaction, anaphylaxis, transfusion-related acute lung injury, TRALI, transfusion-related lung injury, ABO antibody reaction, blood contamination, contaminated blood

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Contributor Information and Disclosures

Author

S Gerald Sandler, MD, FACP, FCAP, Professor of Medicine and Pathology; Director, Transfusion Medicine, Department of Laboratory Medicine, Georgetown University Hospital
S Gerald Sandler, MD, FACP, FCAP is a member of the following medical societies: American Association of Blood Banks, College of American Pathologists, International Society of Blood Transfusions, and Medical Society of the District of Columbia
Disclosure: Nothing to disclose.

Coauthor(s)

Viviana V Johnson, MD, FCAP, Medical Director, Transfusion Services and Armed Services Blood Bank Center, National Naval Medical Center
Viviana V Johnson, MD, FCAP is a member of the following medical societies: American Association of Blood Banks and College of American Pathologists
Disclosure: Nothing to disclose.

Medical Editor

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: Novartis Honoraria Speaking and teaching

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Ronald A Sacher, MB, BCh, MD, FRCPC, Professor, Internal Medicine and Pathology, Director, Hoxworth Blood Center, University of Cincinnati Academic Health Center
Ronald A Sacher, MB, BCh, MD, FRCPC is a member of the following medical societies: American Society of Hematology
Disclosure: Glaxo Smith Kline Honoraria Speaking and teaching; Talecris Honoraria Board membership

CME Editor

Rajalaxmi McKenna, MD, FACP, Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems
Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis
Disclosure: Nothing to disclose.

Chief Editor

Emmanuel C Besa, MD, Professor, Department of Medicine, Division of Hematologic Malignancies, Kimmel Cancer Center, Thomas Jefferson University
Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, and New York Academy of Sciences
Disclosure: Nothing to disclose.

 
 
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