Management of patients refractory to platelet transfusion

Abstract

Refractoriness to infused platelets becomes a major clinical problem for many patients with acute myeloid leukemia (AML). Inadequate post-transfusion platelet count increments can be due to a number of host-related factors such as: splenomegaly, severe infection with high fever, disseminated intravascular coagulation, drug-mediated antibodies and/or alloimmunization, and occasionally by administration of platelets damaged or activated during collection or storage. Lymphocytotoxic antibody directed against HLA-A or -B antigens is an excellent serologic marker for alloimmunization. In one large study, the presence of anti-HLA antibodies was correlated with a poor post-transfusion platelet increase in over 90% of such patients, whereas patients lacking antibodies had satisfactory increments after transfusion 85% of the time.1 Similar predictive information can be obtained using a variety of antiplatelet antibody tests. Post-transfusion counts obtained at the conclusion of transfusion, at a time that the patient must be seen by the physician or nurse to switch infusion bags, are identical to counts obtained 1 h later and it is therefore relatively simple to assess the results of every platelet transfusion to determine if the expected count increment was achieved. 2The incidence of alloimmunization appears to be unrelated to the number of transfusions that patients receive. In a series of 114 newly diagnosed AML patients receiving 2-10+ transfusions of pooled non-leukocyte-depleted platelet concentrates (PC) from random donors, there was no relationship between the number of transfusions or donor exposures, and the development of new anti-HLA antibody.3 At the end of induction therapy, 35-40% of patients had developed antibody. The majority had persistence of the antibody, but 20% had disappearance of antibody over time. After marrow recovery from the induction therapy, 60% of patients remained antibody-negative and, indeed, never developed antibody or refractoriness to platelet transfusion despite multiple subsequent red blood cell and platelet transfusions, suggesting that they had become immune tolerant to histocompatibility antigens. These patients continued to be easily supported with random donor transfusions and therefore measurement of lymphocytotoxic antibody at this time in a patient's treatment course is helpful in predicting and arranging for their future transfusion needs.The traditional management of alloimmune-mediated platelet refractoriness is by HLA typing of donors and recipients. A significant fraction of HLA 'matched' transfusions do not produce satisfactory increments, however, while some 'mismatched' transfusions are successful, and a number of studies have evaluated subtleties of HLA serology to attempt to explain these discrepancies. As one example, there is a high

HLAMatchmaker-driven analysis of responses to HLA-typed platelet transfusions in alloimmunized thrombocytopenic patients

“…Platelet transfusions yielding CCIs of at least 7.5 are generally considered satisfactory. 6 Seventy-four percent of the fully CREG-matched transfusions and 71% of the CREG-incompatible transfusions examined in this study had CCIs greater than 8. Therefore, CREG-based pairing of donor and recipient was associated with minimal likelihood of clinical benefit when this assessment was done at the level of transfusion outcome, as determined by the 15-minute-to-1-hour CCIs.…”

“…The transfusion responses of fully matched donor-recipient pairs (ie, 0 triplet mismatches) were compared with the responses observed when donor HLA antigens were mismatched for no more than 3 or greater than 3 TMMs. 6 Seventy-two percent (n ϭ 378) of the transfusions yielded CCIs of at least 8 (Tables 5 and 6). Transfusions yielding CCIs of at least 8 were associated with significantly less HIMMs (median ϭ 4; first-third quartile, 2-6), compared to those associated with unsatisfactory increments (median HIMMs ϭ 6; first-third quartile, 4-10, t test p 2 value Ͻ .001).…”

“…Matching for HLA-C locus antigens is deemed unnecessary, as HLA-C antigens are expressed at very low levels on platelets and are not considered to play a role in immunologic platelet refractoriness. 2 Guidelines for selecting platelets for HLA-alloimmunized patients have been described in excellent reviews by McFarland, 3 Slichter, 4 Schiffer, 5 and Sacher et al 6 Selection of HLA antigencompatible donors is essential for ensuring satisfactory posttransfusion platelet survivals; donors should lack the antigens against which the patient has made antibodies. [3][4][5][6] When HLA-identical platelet donors are unavailable, the selection of HLA-matched or selectively mismatched platelet donors is based on the segregation of HLA antigens into serologically cross-reactive groups (CREGs).…”

“…2 Guidelines for selecting platelets for HLA-alloimmunized patients have been described in excellent reviews by McFarland, 3 Slichter, 4 Schiffer, 5 and Sacher et al 6 Selection of HLA antigencompatible donors is essential for ensuring satisfactory posttransfusion platelet survivals; donors should lack the antigens against which the patient has made antibodies. [3][4][5][6] When HLA-identical platelet donors are unavailable, the selection of HLA-matched or selectively mismatched platelet donors is based on the segregation of HLA antigens into serologically cross-reactive groups (CREGs). 7 Attention to linked HLA specificities (Bw4/Bw6) is beneficial in some patients unresponsive to cross-reactive platelets, while mismatching for poorly expressed HLA-B locus antigens (eg, HLA-B44, B45) may be acceptable for certain donor-recipient pairs.…”

Platelet Transfusion Refractoriness among Patients with Hematological Malignancies in a Tertiary Center in Saudi Arabia

“…Using HLA A and B antigen matched platelets concentrates is the mainstay of managing such patients, however it leads to satisfactory increments in only half of alloimmunzed patients [28]. Platelet cross-matching is a simple and rapid procedure that can be used to select suitable donor platelets for alloimmunized patients [29,30].…”