Alloimmunization From Transfusions Clinical Presentation

  • Author: Eyal Oren, MD; Chief Editor: Michael A Kaliner, MD   more...
 
Updated: Jan 3, 2012
 

Physical

  • Delayed hemolytic transfusion reactions
    • Hemolysis is usually extravascular, but, in some cases, a component of intravascular hemolysis is present.
    • Most cases manifest during the second week after transfusion, but the reaction can occur from 24 hours to 3 months after the transfusion.
    • Many patients are asymptomatic, and the condition is detected only by laboratory methods.[5]
    • In some patients, fever and/or chills (50%), jaundice (10%), pain (3%), and dyspnea (1%) can occur.
    • Rarely, cases may be complicated with renal failure (6%) or disseminated intravascular coagulation (1%).
    • In patients with sickle cell disease, a DHTR can precipitate sickle crisis.
  • Refractoriness to platelet transfusions
    • Frequently, patients with refractoriness to platelet transfusion are asymptomatic and diagnosed by laboratory methods; however, failure to achieve hemostatic levels of platelets may preclude these patients from important procedures, including bone marrow transplantation. Alloimmunization should be avoided at all costs in candidates for bone marrow transplantation.
    • Preexisting bleeding resulting from thrombocytopenia may persist after transfusion of an appropriate therapeutic dose of platelets.[6] Rarely, spontaneous bleeding may occur after prophylactic transfusion of platelets.
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Causes

  • Alloimmunization to blood antigens occurs after the following:
    • Transfusion
    • Pregnancy
    • Transplantation
    • Sharing intravenous needles (rare)
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Contributor Information and Disclosures
Author

Eyal Oren, MD  Consulting Staff, Institute for Asthma and Allergy

Eyal Oren, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology and American College of Allergy, Asthma and Immunology

Disclosure: Nothing to disclose.

Coauthor(s)

Jorge L Sepulveda, MD, PhD  Associate Professor of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine; Chief, Pathology and Laboratory Medicine Service, Philadelphia Veterans Affairs Medical Center

Jorge L Sepulveda, MD, PhD is a member of the following medical societies: Academy of Clinical Laboratory Physicians and Scientists, American Heart Association, and College of American Pathologists

Disclosure: Nothing to disclose.

Specialty Editor Board

Charles H Kirkpatrick  MD

Charles H Kirkpatrick is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Association of Immunologists, American College of Physicians, American Federation for Clinical Research, American Society for Clinical Investigation, and Clinical Immunology Society

Disclosure: Dyax Consulting fee Consulting

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

Disclosure: Medscape Salary Employment

Samuel R Marney, Jr, MD  Director, Associate Professor, Department of Internal Medicine, Division of Allergy and Immunology, Vanderbilt University School of Medicine

Samuel R Marney, Jr, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American College of Allergy, Asthma and Immunology, American College of Physicians, and Tennessee Medical Association

Disclosure: Nothing to disclose.

Timothy D Rice, MD  Associate Professor, Departments of Internal Medicine and Pediatrics and Adolescent Medicine, St Louis University School of Medicine

Timothy D Rice, MD is a member of the following medical societies: American Academy of Pediatrics and American College of Physicians

Disclosure: Nothing to disclose.

Chief Editor

Michael A Kaliner, MD  Clinical Professor of Medicine, George Washington University School of Medicine; Chief, Section of Allergy and Immunology, Washington Hospital Center; Medical Director, Institute for Asthma and Allergy

Michael A Kaliner, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Association of Immunologists, American College of Allergy, Asthma and Immunology, American Society for Clinical Investigation, American Thoracic Society, and Association of American Physicians

Disclosure: Alcon Consulting fee Consulting; Teva Consulting fee Consulting; Meda Honoraria Speaking and teaching; Ista Consulting fee Consulting; sunovian Consulting fee Consulting; dey Honoraria Review panel membership

References

  1. Henrichs KF, Howk N, Masel DS, Thayer M, Refaai MA, Kirkley SA, et al. Providing ABO-identical platelets and cryoprecipitate to (almost) all patients: approach, logistics, and associated decreases in transfusion reaction and red blood cell alloimmunization incidence. Transfusion. Sep 2 2011;[Medline]. [Full Text].

  2. Gilson CR, Zimring JC. Alloimmunization to transfused platelets requires priming of CD4+ T cells in the splenic microenvironment in a murine model. Transfusion. Oct 7 2011;[Medline].

  3. Buetens O, Shirey RS, Goble-Lee M, Houp J, Zachary A, King KE. Prevalence of HLA antibodies in transfused patients with and without red cell antibodies. Transfusion. May 2006;46(5):754-6. [Medline].

  4. Friedman DF, Lukas MB, Jawad A, Larson PJ, Ohene-Frempong K, Manno CS. Alloimmunization to platelets in heavily transfused patients with sickle cell disease. Blood. Oct 15 1996;88(8):3216-22. [Medline].

  5. Heddle NM, Soutar RL, O'Hoski PL, Singer J, McBride JA, Ali MA. A prospective study to determine the frequency and clinical significance of alloimmunization post-transfusion. Br J Haematol. Dec 1995;91(4):1000-5. [Medline].

  6. Kerkhoffs JL, Eikenboom JC, van de Watering LM, van Wordragen-Vlaswinkel RJ, Wijermans PW, Brand A. The clinical impact of platelet refractoriness: correlation with bleeding and survival. Transfusion. Sep 2008;48(9):1959-65. [Medline].

  7. Allen DL, Samol J, Benjamin S, Verjee S, Tusold A, Murphy MF. Survey of the use and clinical effectiveness of HPA-1a/5b-negative platelet concentrates in proven or suspected platelet alloimmunization. Transfus Med. Dec 2004;14(6):409-17. [Medline].

  8. Novotny VM. Prevention and management of platelet transfusion refractoriness. Vox Sang. 1999;76(1):1-13. [Medline].

  9. Slichter SJ, Davis K, Enright H, Braine H, Gernsheimer T, Kao KJ, et al. Factors affecting posttransfusion platelet increments, platelet refractoriness, and platelet transfusion intervals in thrombocytopenic patients. Blood. May 15 2005;105(10):4106-14. [Medline].

  10. Slichter SJ. Evidence-based platelet transfusion guidelines. Hematology Am Soc Hematol Educ Program. 2007;2007:172-8. [Medline].

  11. Poon MC. The evidence for the use of recombinant human activated factor VII in the treatment of bleeding patients with quantitative and qualitative platelet disorders. Transfus Med Rev. Jul 2007;21(3):223-36. [Medline].

  12. Schonewille H, Haak HL, van Zijl AM. Alloimmunization after blood transfusion in patients with hematologic and oncologic diseases. Transfusion. Jul 1999;39(7):763-71. [Medline].

  13. Werch J. Use of Rh immune globulin when transfusing large volumes of Rh-positive cells. Am J Clin Pathol. May 1999;111(5):712. [Medline].

  14. Werch J, Todd C. Resolution by erythrocytapheresis of the exposure of an Rh-negative person to Rh-positive cells: an alternative treatment. Transfusion. Jun 1993;33(6):530-2. [Medline].

  15. Wahl S, Quirolo KC. Current issues in blood transfusion for sickle cell disease. Curr Opin Pediatr. Feb 2009;21(1):15-21. [Medline].

  16. The Trial to Reduce Alloimmunization to Platelets Study Group. Leukocyte reduction and ultraviolet B irradiation of platelets to prevent alloimmunization and refractoriness to platelet transfusions. N Engl J Med. Dec 25 1997;337(26):1861-9. [Medline].

  17. Friedberg RC. Clinical and laboratory factors underlying refractoriness to platelet transfusions. J Clin Apher. 1996;11(3):143-8. [Medline].

  18. Blumberg N, Heal JM, Gettings KF. WBC reduction of RBC transfusions is associated with a decreased incidence of RBC alloimmunization. Transfusion. Jul 2003;43(7):945-52. [Medline].

  19. Delaflor-Weiss E, Mintz PD. The evaluation and management of platelet refractoriness and alloimmunization. Transfus Med Rev. Apr 2000;14(2):180-96. [Medline].

  20. Kekomaki R. Use of HLA- and HPA--matched platelets in alloimmunized patients. Vox Sang. 1998;74 Suppl 2:359-63. [Medline].

  21. Kickler T, Herman JH, eds. Current issues in platelet transfusion therapy and platelet alloimmunity. Bethesda, Md: AABB Press; 1999.

  22. Legler TJ, Fischer I, Dittmann J, Simson G, Lynen R, Humpe A. Frequency and causes of refractoriness in multiply transfused patients. Ann Hematol. Apr 1997;74(4):185-9. [Medline].

  23. Pineda AA, Vamvakas EC, Gorden LD, Winters JL, Moore SB. Trends in the incidence of delayed hemolytic and delayed serologic transfusion reactions. Transfusion. Oct 1999;39(10):1097-103. [Medline].

  24. Sayeh E, Sterling K, Speck E, Freedman J, Semple JW. IgG antiplatelet immunity is dependent on an early innate natural killer cell-derived interferon-gamma response that is regulated by CD8+ T cells. Blood. Apr 1 2004;103(7):2705-9. [Medline].

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  26. Schonewille H, van de Watering LM, Brand A. Additional red blood cell alloantibodies after blood transfusions in a nonhematologic alloimmunized patient cohort: is it time to take precautionary measures?. Transfusion. Apr 2006;46(4):630-5. [Medline].

  27. Warkentin TE, Smith JW. The alloimmune thrombocytopenic syndromes. Transfus Med Rev. Oct 1997;11(4):296-307. [Medline].

 
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Table 1. Human Platelet-Specific Antigen Systems
Platelet Antigen SystemProtein AntigenSynonymsAllelesAntigen Frequency
HPA-1GPIIIaPlA,ZwHPA-1a = PlA1



HPA-1b = PlA2



97%



26%



HPA-2GPIbKo, SibHPA-2A



HPA-2b



99%



14%



HPA-3GPIIbBak, LekHPA-3a



HPA-3b



85%



66%



HPA-4GPIIaPen, YukHPA-4a



HPA-4b



>99%



< 1%



HPA-5GPIaBr, Hc, ZavHPA-5a



HPA-5b



99%



20%



Table 2. Frequent Clinically Significant Anti-RBC Antibodies
AntigenSystemFrequency Among All Detected AlloantibodiesFrequency of Antigen



(Whites)



Frequency of Antigen



(Blacks)



Potency*
ERh16-40%30%2%4%
Kell (Kl)Kell5-40%9%3%9%
DRh8-33%85%92%70%
cRh4-15%80%99%4%
Jk(a)Kidd2-13%77%91%0.14%
Fy(a)Duffy4-12%63%10%0.46%
CRh2-10%70%32%0.22%
eRh2-3%98%98%1%
Jk(b)Kidd2%72%43%0.06%
SMNSs1-2%55%31%0.08%
sMNSs< 1%89%97%0.06%
*Percentage of antigen-negative recipients who become alloimmunized if transfused with antigen-positive units
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