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Platelet Refractoriness

Posted May 1, 2011

Kyle M. Annen, DO

Platelet refractoriness is the repeated failure to obtain satisfactory response to platelet transfusion.1 A variety of immune and nonimmune conditions can account for inadequate platelet response, and usually the reasons are multifactorial. Nonimmune causes are by the far the most common: They include splenomegaly, fever, sepsis, disseminated intravascular coagulation, infection, bleeding, graft-versus-host disease, and medications, particularly vancomycin, sulfonamides and heparin.3,4 Immune causes, specifically human leukocyte antigen (HLA) antibodies should be considered after nonimmune possibilities are ruled out.

The occurrence of two or more consecutive platelet transfusions with a lower response than expected should raise a concern for platelet refractoriness.3 After a platelet apheresis unit or a six-unit pool of whole blood derived platelets, an increment of 30,000-50,000 platelets/µL is expected. A post-transfusion platelet count at 10-60 minutes is critical to evaluate the response. Objectively, a corrected count increment (CCI) of less than 5-10 × 109/l after at least two to three platelet transfusion episodes suggests platelet refractoriness.

CCI = Post-Transfusion Platelet Increment (109/l) x Body Surface Area (m2)
1011 Transfused Platelets

The presence of HLA class I antibodies is the most common immune reason for platelet transfusion refractoriness and accounts for 30-40% of all cases. HLA antibodies result from exposure to leukocytes in transfused blood products, transplantation, or pregnancy. Screening for HLA class I antibodies is performed via a variety of methods, including lymphocytotoxity testing and enzyme-linked immunosorbent assay (ELISA).Platelet transfusion refractoriness can be caused by an antibody to a specific HLA antigen, but it usually occurs due to mutiple antibodies. The panel reactive antibody (PRA) represents the percentage of individuals with whom the patient’s HLA antibodies react; a PRA result of >20% suggests HLA alloimmunization. Once the blood bank confirms a diagnosis of HLA platelet refractoriness, HLA-matched platelets can be used. Depending on the patient’s phenotype and product availability, products may not be easily accessible.

When an immune cause is suspected, it is important to involve the blood bank medical director in order to proceed efficiently. The above tests to determine an immune cause for platelet refractoriness and to obtain the appropriate platelet product may take several days, a significant concern if the patient is actively bleeding. ABO-compatible and “fresh” platelets (ie, stored for less than 48 hours) are associated with a significant improvement in post-transfusion CCI5 and should be used while diagnosis and workup are in progress. Platelet products available for treatment include HLA-matched platelets (once HLA phenotype is known), crossmatched platelets (used for both diagnosis and treatment), or HLA antigen negative platelets (if antibody specificity is known). An important part of the support of the refractory patient is to transfuse platelets to control hemostasis rather than to obtain a desired platelet count.6

Crossmatched platelets (where donor platelets are mixed with patient plasma to determine if compatible) may be obtained more quickly than HLA matched platelets. In addition, crossmatched platelets can be used both for diagnosis and treatment, as antibody detection is inherent to its testing process; in some institutions this may provide faster turnaround time. Crossmatched products have been shown to have a longer survival post-transfusion than unmatched platelets.3 Crossmatched platelets are typically available within several hours, whereas HLA-matched platelets may take several days to obtain. Another benefit of crossmatching as compared to providing HLA-matched platelets is the potential larger pool of compatible donors.

A newer strategy for managing alloimmunization is antibody specificity prediction (ASP). The HLA specificities of the recipient’s alloantibodies are determined, and the patient is transfused with platelets from donors lacking those HLA antigens. The main advantage of the ASP method is associated with the increase in the availability of donors.3 As new techniques and therapies are developed, the available donor population will continue to expand and thus improve the options for patients with platelet refractoriness.

References and Suggested Reading

  1. Doughty HA, Murphy MF, Metcalfe P, et al. Relative importance of immune and non-immune causes of platelet refractoriness. Vox Sang. 1994;66:200–205.
  2. McFarland JG. Matched apheresis platelets. In: McLeod B and Price TH, eds. Apheresis: Principles and Practice. 3rd ed. Bethesda, MD: AABB Press; 2010.
  3. Hod E, Schwartz J. Platelet transfusion refractoriness. Br J Haematol. 2008;142:348–360.
  4. Hendrickson JE, Roback J. Platelet transfusion refractory patients. In: Hillyer CD, Shaz BH, Zimring JC, et al. Transfusion Medicine and Hemostasis, Clinical and Laboratory Aspects. New York, NY: Elsevier; 2009:283–286.
  5. Slichter SJ, Davis K, Enright H, et al. Factors affecting posttransfusion platelet increments, platelet refractoriness, and platelet transfusion intervals in thrombocytopenic patients. Blood. 2005;105:4106–4114.
  6. Dzik S. How I do it: platelet support for refractory patients. Transfusion. 2007;47:374–378.

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NewsPath® Editor: C. Leilani Valdes, MD
This newsletter is produced in cooperation with the College of American Pathologists Public Affairs Committee and the NewsPath Editorial Board and may be reproduced in whole or in part as a service to the medical community. Copyright © 2011 by the College of American Pathologists.
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