Case Presentation: A 37 year-old man presented with altered mental status and a headache after a motor vehicle collision where he was a restrained driver while intoxicated with alcohol. He had a known history of glucose-6-phosphate-dehydrogenase deficiency (G6PD). Exam was notable for superficial abrasions on bilateral upper and lower extremities, diffuse generalized abdominal tenderness to palpation, and general intoxication, but he was oriented and arousable. Vital signs were within normal limits. Laboratory data revealed thrombocytopenia with a platelet count of 10 K/µL, hemoglobin of 9.1 g/dL and creatinine of 1.59 mg/dL. Lactate dehydrogenase was elevated to 868 U/L and haptoglobin was low at 18 mg/dL. Schistocytes were seen on peripheral smear. On imaging he was found to have subarachnoid hemorrhage, as well as hemorrhagic areas of liver, left kidney, and left acetabulum. He was treated with intravenous dexamethasone and intravenous immunoglobulin for suspected immune thrombocytopenic purpura (ITP) and experienced full recovery in platelet count and renal function in the first five days. However, after this initial response, platelet counts began to drop precipitously. ADAMTS13 levels were found to be markedly diminished at 3.6%. Despite the atypical presentation for thrombotic thrombocytopenic purpura (TTP) and other possible etiologies including refractory ITP, disseminated intravascular coagulation, G6PD and alcohol abuse, he was started on plasma exchange (PEX). He experienced full platelet count recovery after nine rounds of PEX and was discharged on a steroid taper.
Discussion: TTP is caused by decreased activity of the von-Willenbrand factor cleaving protease ADAMTS13, resulting in increased von-Willenbrand factor with associated microangiopathic hemolytic anemia (MAHA) and thrombocytopenia. Though historically associated with a pentad of MAHA, thrombocytopenia, fever, acute renal failure, and neurologic findings, these criteria have become largely obsolete in diagnosing TTP as earlier diagnosis and treatment can prevent these symptoms from occurring and initial manifestations can be subtle. Decreased levels of ADAMTS13 are classic for diagnosis of TTP but often are not readily available and therapy should not necessarily be delayed for this confirmatory result. The mainstay of therapy for TTP is PEX, with adjunctive therapy of steroids and rituximab. PEX replaces ADAMTS13 and removes autoantibodies inhibiting ADAMTS13 which allows for cleavage of von-Willebrand factor multimers. Initiation of PEX is urgent and lifesaving, without which the mortality rate from TTP is 90%. IVIG is not indicated for treatment of TTP, and treatment with IVIG and steroids would not be expected to result in platelet recovery or improvement, though in rare cases they temporarily can.
Conclusions: Hospitalists often encounter situations where initial therapeutic interventions fail and are forced to widen their differential diagnosis. Revisiting the differential can allow for recognition of life-saving interventions, and it is often the hospitalist who is at the forefront of making such connections.