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Platelet Refractoriness

Alloimmunization against histocompatibility antigens occurs in 25 to 35% of patients with acute leukemia who are transfused with multiple random donor platelet transfusions and in 4 to 5% transfused with apheresis platelets. This is the most important long-term complication of platelet transfusions because patients become refractory to future platelet transfusions.

An adult patient is considered to be refractory if the 10-60 minute post-transfusion platelet count fails to rise more than 2000/uL per random platelet concentrate or 10, 000 to 12, 000/uL per apheresis platelet. Children are considered to be refractory if the one hour post-tranfusion platelet count fails to rise more than 3500/uL per random donor platelet concentrate. Because patients may have a poor post-transfusion increment to a single transfusion yet have excellent platelet increments with subsequent transfusions, a diagnosis of refractoriness should only be made when at least two ABO compatible transfusions, stored less than 72 hours, result in poor increments.

Other causes of platelet destruction should also be ruled out including:

  • Fever
  • Sepsis,
  • Splenomegaly
  • DIC
  • Bleeding
  • Status post-BMT
  • Alloimmunzation
  • Drug induced immune thrombocytopenia.

The diagnosis of refractoriness should be confirmed by testing for platelet antibody, which detects antibody to HLA and platelet-specific antigens. Approximately 90% of alloimmunized patients will have demonstrable platelet antibody.

If the platelet antibody test is positive, a refractory patient is best managed by transfusion of crossmatch compatible apheresis platelets. There is no evidence that alloimmunized patients benefit from continued prophylactic transfusion of incompatible platelets that do not produce an increase in posttransfusion platelet count.

If there is an inadequate post transfusion platelet count increment following 4 consecutive crossmatch compatible single donor platelets, it is reasonable to revert to the use of randomly selected products. It is important to obtain platelet counts 10 minutes to 1 hour following each transfusion of compatible platelets since a useful but temporary post transfusion increment may occur but be missed if platelet counts are not obtained until the next morning.

Several anecdotal strategies have been reported for controlling bleeding in thrombocytopenic patients when compatible platelet donors cannot be found in a timely manner. Transfusion of RBCs to increase the hematocrit to 30% or higher prior to platelet infusion, increases the likelihood of platelet contact with the endothelial surface of blood vessels (Ho CH, Transfusion 1998;38:1011-14). Some patients may benefit from repeated bolus doses of apheresis platelets. Large numbers of platelets may adsorb much of the circulating platelet antibody (Nagasawa T, Transfusion 1978;18:429-35). Transfusing platelets slowly over six hours has been advocated (Narvios A, Am J Hematol 2005;79:80). Concomitant administration of antifibrinolytic medication, such as Amicar, may also decrease bleeding (Kalmadi S, Cancer 2006; 107:136-40). Intravenous immune globulin and plasma exchanges have not been found to be effective in reducing the refractory state.

If the platelet antibody screening test is negative, refractoriness is probably due to clinical factors rather than alloimmunization and crossmatched platelets will not be beneficial.

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