A 68-year-old African-American man was initially admitted with atrial flutter and was started on anticoagulation treatment, which was complicated by hematemesis requiring transfer to our intensive care unit (ICU) on day 4 of hospitalization. He had a past medical history of packed red blood cell (PRBC) transfusion in 2002. On admission, his blood count showed hemoglobin 13.6g/dL, red blood cell count 5.14 × 1012/L, and platelets 265 × 109/L. His prothrombin time was 17.6 seconds (normal range: 11.8 to 14.5 seconds), activated partial thromboplastin time was 30.4 seconds (normal range: 23.0 to 35.0 seconds) and international normalized ratio was 1.5. His ICU course was further complicated by Moraxella catarrhalis pneumonia, for which he completed a course of imipenem, and by Clostridium difficile colitis treated with oral vancomycin. While in the ICU, our patient received six units of PRBC and two units of plasma on day 4 of hospitalization, six units of PRBC on day 5 and six units of plasma on day 13 and day 14. He clinically improved and was transferred to the medical ward on day 21. His platelet count began to drop rapidly on day 25 and on day 29 his platelets decreased to 51 × 109/L and he developed hematuria. He was afebrile and had no signs of infection. On day 30, his platelet count dropped to 31 × 109/L. His prothrombin time and activated partial thromboplastin time were normal. A peripheral blood smear was remarkable for large platelets that were decreased in number. The differential diagnosis at this time included drug-related thrombocytopenia, PTP and immune thrombocytopenic purpura. Several medications were discontinued. However, his platelet count continued to drop, reaching a nadir of 7 × 109/L on day 32. On that same day, our patient received methylprednisolone 1mg/kg and one unit of single-donor platelets. On day 33, intravenous immune globulin (IVIg) was begun at a dose of 700mg/kg daily for three doses. Two days after the first dose of IVIg, his platelet count increased to 46 × 109/L without further transfusions and the hematuria resolved. An enzyme-linked immunosorbent assay for antibodies to platelet surface glycoproteins demonstrated the presence of an antibody with reactivity to HPA-5b. Prior to the administration of IVIg, an antibody with reactivity to HPA-5b was detected by a solid-phase enzyme-linked immunoassay commercial kit (Gen-Probe, Inc., San Diego, CA, USA), cleared for in vitro diagnostic use by the US Food and Drug Administration. The absorbance (optical density) of our patient’s sample was 0.27 (negative control: 0.13). Our patient’s platelet genotyping by polymerase chain reaction and fluorescent hydrolysis revealed HPA-5a/5a (Mayo Clinic Laboratories, Rochester, MN, USA). Methylprednisolone was discontinued on day 34 of admission. On day 36, our patient was discharged without bleeding manifestations and with a platelet count of 61 × 109/L. Twenty-two days after discharge, his platelet count had increased to 280 × 109/L.