An evaluation of crossmatching, HLA, and ABO matching for platelet transfusions to refractory patients

Refractoriness occurs in many patients receiving multiple platelet transfusions. We used a sensitive ELISA assay to assess the utility of crossmatching HLA-A,B matched single donor platelets in 51 consecutive, typical refractory patients. Of the 222 transfusions evaluated at 1 to 4 hours posttransfusion, only 1 7 of 54 (31 %) with positive crossmatches had corrected platelet count increments of �7.5OO/�L. In contrast, 95 of 168 (57%) of those with negative crossmatches had such increments (P < .001). Regardless of the results of the crossmatch, HLA-A.B, and ABO matching had independent influences on transfusion outcome. The median corrected 1- to 4-hour increment for crossmatch negative transfusions was 13,300/sL for A/BU grade matches, 9,700 for BX, and7,800 for C. Increments were 10,00O/�sL for ABO-identical transfusions and 5,900 for transfusions of platelets ABO incompatible with the recipient’s plasma antibodies. When the donor platelets were ABO compatible, but the donor plasma contained S INCE THE l960s, platelet transfusion therapy has become vital to the prophylaxis and therapy of bleeding disorders in patients with leukemia, aplastic anemia, some lymphomas, and solid tumors.’ The availability of effective platelet transfusion products has decreased mortality from bleeding in these patients.2 Perhaps 50% of multiply transfused patients become clinically refractory.3’4 The causes of refractoriness to platelet transfusion appear to be primarily immunological,5 although factors other than alloimmunization may play an important role.6 HLA-A,B matching is one approach that has been fruitful in dealing with some refractory patients.7 Recently, questions have been raised as to whether refractoriness to platelet transfusion occurs purely on the basis of immunologic mechanisms.8 Such doubts are reasonable because the patients in question often have fever, infection, bleeding, coagulopathy, and splenomegaly. These nonimmunologic factors are known to decrease platelet recovery and survival. Sensitive and specific crossmatch techniques are now available for detection of IgG and 1gM binding to donor platelets.9’ ‘ These tests appear to predict posttransfusion survival of platelets in patients with alloantibodies to donor platelets. However, many published studies excluded patients with the previously mentioned common factors that contribute to increased platelet consumption. Therefore, only a very small subset of refractory patients has been examined in detail. We developed a sensitive enzyme-linked antiglobulin assay, and used it to evaluate platelet crossmatching retrospectively in typical refractory patients. We did not exclude any patients, because the utility of crossmatching in refractory patients preselected on the basis of alloimmunization has been clearly demonstrated.9 We reasoned that a study that does not exclude any patients would yield a realistic assessment of the potential benefits of crossmatching in typical clinical practice. It might also provide useful insights into the refractory state that could be missed if the study ABO antibodies to the recipient’s platelets, the increment was intermediate (8,200/�zL). The most important factor in predicting platelet survival was the crossmatch, followed by HLA-A,B and ABO. each having independent predictive value. These data demonstrate that the predictive value of a negative crossmatch may be considerably less than that reported in previous studies with stable, less ill patients. In typical refractory patients, there appear to be mechanisms of platelet destruction that are related to HLA-A,B and ABO but are not detected with current crossmatch methods. We hypothesize that soluble plasma HLA-A.B and ABO antigens contribute to the destruction of donor and sometimes recipient platelets by an immune complex or other “innocent bystander” mechanism. With our crossmatching technique, HLA-A,B and ABO match grades remain rolevant to platelet transfusion therapy in some refractory patients. Ia 1987 by Grune & Stratton. Inc.