CD36 (Naka) Sensitization with Platelet-Transfusion Refractoriness in a Liver Transplant Recipient

We report here an unusual case of a liver transplantation followed by anti-CD36 (GP IV, Naka) sensitization, probably from transfusion, and involving platelet-transfusion refractoriness (PTR). A 47-year-old Japanese man with hepatitis B virus-related liver cirrhosis received a liver transplant in 2001 from his 52-year-old brother with one human leukocyte antigen (HLA) locus mismatch (Table 1). After the transplantation, the patient’s platelets dropped to 2×1010/L, and platelets were transfused frequently to keep the count at an acceptable level. The number of platelets fluctuated between 2 and 4×1010/L with a transient rise to 10×1010/L after transfusion, indicating a poor response to transfusions of random-donor platelets. No obvious bleeding episodes were observed. Anti-CD36 iso-antibody, which was negative before and 5 days after the transplantation, was first detected after 8 days. Platelets from 21 donors had been transfused by day 8. The recipient was administered immunosuppressants, and tacrolimus (4 mg/day) was changed to prednisolone (5 mg/day) on day 7 because of liver dysfunction. The titer of the antibody, which was ×16 on day 8, went up to ×128 on day 22. No anti-HLA or anti-human platelet antigen (HPA) was detected throughout the period. The recipient and the liver donor were negative for CD36 antigen. The patient was transfused effectively with platelets from CD36 negative, but HLA nonselected, donors. After day 99 when the titer went down to ×16, the platelet count persisted at approximately 4 to 5×1010/L without frequent transfusions. There was no clear evidence of sepsis or rejection during the clinical course. The titer of anti-CD36 declined gradually after CD36-negative transfusion and disappeared on day 232. Nevertheless, the low platelet count was not resolved completely. The patient died of multi-organ failure on day 377.TABLE 1: Inspection results of the recipient and donorAlloimmune thrombocytopenias in adults are classified into posttransfusion purpura, passive alloimmune thrombocytopenia, transplantation-associated alloimmune thrombocytopenia, and PTR. Transplanted solid organs contain passenger lymphocytes that can transmit autoimmune disease or initiate alloimmune disorders in recipients. Alloimmune thrombocytopenia is an uncommon, but not rare, cause of thrombocytopenia. Alloantibodies against platelet-specific alloantigens, in particular HPA-1a among white populations, can cause severe thrombocytopenia in recipients. PTR usually results from various antiplatelet antibodies related to frequent platelet transfusions (1). Antibodies to HLA are the most common cause, and platelet-specific allo- or iso-antibodies, such as anti-CD36, can also give rise to PTR in combination with anti-HLAs. CD36 is localized on platelet GP IV (2), which is an 88 kDa glycoprotein expressed on platelets and monocytes/macrophages. There are two types of CD36 deficiencies. In type I, CD36 is absent from both platelets and monocytes, whereas it is absent only from platelets in type II deficiency (3). It has been reported that 5% to 10% of Asians and approximately 2.4% of African Americans have platelets lacking the major membrane GP IV that carries CD36 (4). In the Japanese population, the frequencies of type I and type II deficiencies are 0.54% and 4.0%, respectively (3). Although individuals with CD36 deficiency are apparently healthy with no obvious bleeding tendency, type I deficiency may potentially result in the production of anti-CD36 after transfusion or pregnancy (3). In our case, only anti-CD36 was produced with no anti-HPA or anti-HLA. Although it was a very rare case (5), anti-CD36 antibody in the recipient that was caused by frequently transfused CD36-positive platelets of random-donors resulted in PTR. As far as we know, this is the first case of PTR caused by anti-CD36 in a liver transplant recipient. Takashi Ogata Hitoshi Ohto Hiroyasu Yasuda Kinuyo Kawabata Division of Blood Transfusion and Transplantation Immunology Fukushima Medical University School of Medicine Fukushima, Japan Takao Tsuchiya Takuro Saito Mitsukazu Gotoh Department of Surgery I Fukushima Medical University School of Medicine Fukushima, Japan