Platelet Refractoriness Due to Anti-CD-36(NAKa) Ameliorated By Platelet Washing
Authors: Sahai Tanmay , Masel Debra , Henrichs Kelly F , Schmidt Amy E , Refaai Majed A. , Kirkley Scott A. , Mendler Jason H. , Blumberg Neil 
Published: November 2019

Introduction:

Platelet transfusion refractoriness in patients with hematological malignancies ranges from 7-34% (Blood 2015; 126:3484). The etiology of platelet refractoriness in this patient population is typically due to formation of HLA antibodies from pregnancy or previous transfusion. Although these patients receive leukoreduced products, alloimmunization is not completely prevented. We report platelet refractoriness in the setting of induction chemotherapy for acute myeloid leukemia (AML) from alloantibodies to NAKa antigen/CD-36/glycoprotein (GP) IV. We propose that washing platelets may be a potential strategy for treating platelet refractoriness in patients with NAKaantibodies as finding CD36 negative donors is extremely difficult and few blood banks in North America test donors for this antigen.

Case:

A 66 year old African American female presented with pancytopenia requiring transfusions. She was later diagnosed with AML with 70% circulating peripheral blasts and started on 7+3 regimen (Cytarabine for 7 days and Idarubicin for 3 days). She developed profound thrombocytopenia by day 7 and her platelet count was 0 by day 13. She was refractory to platelet transfusion from the outset. An Immucor ELISA assay was positive for anti-GPIV (NAKaantigen/CD-36). No antibody to GPIIb/IIIa, GPIa/IIa, GPIb/IX, and HLA Class I was present. Anti-GPIV was confirmed by Blood Center of Wisconsin utilizing monoclonal antibody MBC 131.7 (produced by Blood Center of Wisconsin) directed against CD36. Cross-matching was performed at our institution with multiple single donor apheresis platelets, all showing strong positive reactivity. Given the patient's low platelet count and onset of urinary tract bleeding, an incompatible leukoreduced, irradiated, and washed single donor platelet unit was given. The patient tolerated the transfusion with no adverse events noted during or after transfusion. The patient's platelet count rose from < 1 to 14,000/µL when measured 4 hours after the transfusion, and her count was sustained through the following day. Despite the strong, positive reactivity of this unit at crossmatch testing, this was the first successful response to multiple platelet transfusions. Unfortunately, her percentage of blasts in the peripheral blood increased and she maintained an absolute neutrophil count of 0. The patient and hematology team decided to switch to hospice as her AML was resistant to therapy and unfit for any other myelotoxic regimens. Her platelet count was checked the following week and it was 16,000/µL despite no transfusion support.

Discussion:

Platelet refractoriness in the setting of hematological malignancy has been well documented. Alloantibodies develop from prior pregnancy, prior transfusion or multiple transfusions in the setting of prolonged pancytopenia in hematological malignancies, especially AML. Typically, antibody develops against platelet membrane polymorphic structures including human platelet, ABO, HLA, and very rarely NAKa antigens on the CD36 glycoprotein molecule. CD36 is expressed in almost 100% of white Europeans and is not expressed by 2% of sub-Saharan Africans and 10% of Asians (Blood Transfus 2015: 13: 380). In screening of 871 US blood donors, Yamamoto et al. identified three platelet CD36 deficient individuals. Thus finding a CD36 negative platelet donor will most likely take an extended amount of time, which could be a challenge in these patients as bleeding risk is high during or after induction chemotherapy. CD36 is a soluble antigen and is expressed on various cells such as erythroblasts and monocytes. It has been proposed that when ABO mismatched platelets are transfused, circulating immune complexes may form between the soluble ABH antigens and the transfused antibody. Platelets may then be destroyed by binding of immune complexes to the Fc and C1q receptors. We speculate that a similar pathophysiology may occur in CD36 deficient patients as circulating anti-CD36 forms immune complexes with donor soluble CD36 antigen. Washing will remove most soluble CD36 and potentially mitigate the effect of immune complex formation. Based upon the limited experience with this patient, we suggest that washing in this setting may be beneficial and yield a sustained, incremental response in the platelet count in patients with platelet refractorinesssecondary to anti-NAKa.

Disclosures

Blumberg: Biomet/Citra Labs: Consultancy, Honoraria.