Alloimmunization From Transfusions Treatment & Management

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

Medical Care

  • Delayed hemolytic transfusion reactions
    • Most patients tolerate DHTR well and only require observation and supportive care.
    • Good communication with a blood bank is essential to attempt to provide transfusion support with antigen-negative RBCs. If these RBCs are not available, weigh the risk of further hemolysis against the indications for transfusion.
    • If the load of antigen-positive packed RBCs is large (>5 U), consider exchange transfusion. Administer intravenous human immunoglobulin (IVIG) to block further hemolysis in cases in which antigen-positive blood is transfused. The IVIG dose is 400 mg/kg, infused slowly within 24 hours posttransfusion.
  • Refractoriness to platelet transfusions
    • Avoiding the use of platelet transfusions as much as possible is important in alloimmunized patients. Preventive transfusions are not recommended. Measures to minimize the likelihood and extent of bleeding (eg, rapid treatment of infection; avoidance of invasive procedures; correction of coagulation deficiencies, anemia, and renal insufficiency; use of antifibrinolytic agents) should be used extensively.
    • After diagnosing alloimmune platelet refractoriness, use the sequence of measures that follows, initiating each subsequent intervention if the previous one fails.
      • Rule out nonimmune, autoimmune, and drug-related causes of platelet refractoriness, or treat accordingly. Providing immune-compatible platelets is unlikely to be effective in the presence of nonimmune causes of refractoriness.
      • Consider alternatives to platelet transfusion to control bleeding, including the use of antifibrinolytic agents such as alpha-aminocaproic acid, or activated recombinant factor VIIa.[11]
      • Transfuse ABO-compatible fresh (aged < 48 h) platelet concentrates. ABO-matched and fresher platelets result in more recoveries than mismatched and older (aged >3 d) platelets.
      • Transfuse with platelets from blood relatives. Obtaining platelets from blood relatives is worthwhile because the chance of matching 2 or more HLA and platelet antigens is high (resulting in good recovery) and relatives are often willing to donate frequently. Irradiation of blood products from relatives is mandatory to prevent graft versus host disease.
      • Select HLA-matched platelets. Perform HLA typing of patients who receive multiple transfusions before they become pancytopenic. Matching for both private (ie, HLA-A, HLA-B) and public (ie, cross-reacting groups) antigens is best achieved by computerized selection of donors, based on the results of the PRA assay.
      • Select crossmatched platelets. Crossmatch-compatible platelets can significantly improve platelet recovery in approximately 50% of patients who are refractory to random-donor platelets. Selecting crossmatched platelets is indicated especially for patients with high PRA levels or those who do not respond to HLA-matched platelets.
      • The use of HPA1a/5b-negative platelets has been successful in cases of posttransfusion purpura and neonatal platelet alloimmunization. These antigens are involved in most (95%) cases of neonatal or posttransfusion purpura, but they represent no more than 10-20% of immune refractoriness to platelet transfusions.
      • Pretreat with IVIG before transfusion. IVIG pretreatment can result in successful recovery after platelet transfusion in patients who are alloimmunized. Success rates vary (as much as 70%) and depend on the degree of alloimmunization. IVIG does not reduce the number of alloantibodies but does decrease platelet-associated immunoglobulins and possibly interferes with platelet destruction mechanisms. IVIG is more effective in improving short-term (1-6 h) recovery of platelets than platelet survival (>24 h).
      • Use high-dose platelet transfusion. Empirical use of high doses of random platelet units (eg, 1 unit/10 kg tid or 2-3 units/10 kg before invasive procedure) may result in titration of the antibody, overwhelming of the mononuclear-phagocyte system, and increased survival of transfused platelets.
      • Attempt large-volume plasmapheresis. Plasmapheresis (eg, 2 plasma volumes for 1-3 d) before bone marrow transplantation results in beneficial responses in most patients who are alloimmunized to platelets. Perfusion of the plasma through a staphylococcal protein A column is an experimental treatment undergoing evaluation.
      • Consider administering immunosuppressive drugs. While steroids are not effective, isolated reports suggest that immunosuppressive therapy is effective for reverting platelet refractoriness. The use of vincristine and cyclosporin A has been successful but requires 2-3 weeks to take effect.
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Consultations

Transfusion medicine specialist or hematologist

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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

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  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].

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

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  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].

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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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