HLA- and HPA-Alloimmunization Rate In the Setting of Refractoriness to Platelet Transfusion: A Single Center Study,

Refractoriness to platelet transfusion is a common clinical problem occurring in up to 34% of hematology/oncology patients (Hod and Schwartz 2008). While often non-immunologic in etiology, alloimmunization to human leukocyte antigens (HLA) or human platelet antigens (HPA) may contribute to this phenomenon. If patients are refractory to pooled, random donor platelets, most institutions have an explicit algorithm which facilitates a supply of single-donor (SD) apheresis and/or HLA-matched platelets. At our institution, platelet refractoriness is defined as a platelet count rise of <10×10⁹/L measured within 24 hours post-transfusion of ABO-matched single-donor platelets on at least two occasions. In this circumstance, HLA matched platelets have been provided regardless of the HLA/HPA alloimmunization status. The goal of this study was to measure the HLA- and HPA-alloimmunization rates in adult patients at our institution who were refractory to single donor platelet transfusions.

All patients at our centre who were refractory to single donor platelet transfusion between January 2006 and June 2011 were included. Patients were tested for the presence of HLA and HPA antibodies at the Canadian Blood Services Platelet Immunology Laboratory. HLA typing was performed by molecular SSO/SSP method and antibody identification was achieved using Luminex single antigen assay following an initial screening test. HPA antibody determination was performed by ELISA. For patients with HLA antibodies, panel reactive antibody (PRA), which estimates the percentage of potential reactivity against donors in the population, was calculated using cPRA software from the Organ Procurement Transplantation Network (OPTN).

Thirty-three patients (18 male and 15 female) were tested for HLA and HPA antibodies in the setting of platelet transfusion refractoriness. All patients received multiple blood transfusions prior to becoming refractory to platelets. Most patients (85%; 28/33) had a hematologic malignancy (leukemia (19), lymphoma (5), myelodysplastic syndrome (2), myelofibrosis (1), and amyloidosis (1)) while five patients had non-malignant hematological disorders (aplastic anemia (3), antiphospholipid syndrome (1), and congenital pancytopenia (1)). No HPA antibodies were identified in any patient. HLA antibodies were found in 42% of patients (14/33) and was different according to gender: 22% for males (4/18) vs 67% for females (10/15). Males (n=4) were found to be mildly to moderately sensitized to HLA with an average PRA of 33% (range 11–62%). Nine out of 10 females were highly sensitized to HLA with PRA values between 95 and 100%. There was no association between the presence of HLA antibodies and either patient diagnosis or a history of allogeneic stem cell transplantation.

We have demonstrated a relatively high rate of HLA alloimmunization (42%) among patients refractory to single donor platelets compared to previously published reports. This may be due to differences in testing methodology and/or stringency of the definition of platelet transfusion refractoriness. Similar to other studies, we found no significant contribution of HPA antibodies to platelet refractoriness in our patient population. Patient diagnosis and/or history of allogeneic stem cell transplantation did not appear to influence the rate of HLA alloimmunization. Importantly, we found that the majority of refractory patients with HLA-antibodies and high level of HLA sensitization (PRA ≥ 95%) were female (64%; 9/14), implicating pregnancy as a possible contributor to immunologically-based platelet transfusion refractoriness. The finding of high PRA values (≥ 60%) in the majority of HLA-sensitized patients (71%, 10/14) argues against the utility of platelet crossmatching for identification of HLA compatible platelets. In addition, the marked differences in the incidence and the extent of HLA sensitization between male and female patients suggests that gender should be added as an important factor in HLA-matching algorithms for the purposes of platelet transfusion support in refractory patients to optimize the use of HLA-matched platelet donors.

No relevant conflicts of interest to declare.