INTRODUCTION: Thrombotic thrombocytopenic purpura (TTP) is a life threatening condition characterized by microangiopathic hemolytic anemia (MAHA) and thrombocytopenia with variable degrees of neurological dysfunction, renal failure and fever. However, diagnosis of TTP can be challenging because of its unusual clinical presentations. We describe an atypical case of TTP in whom early diagnosis and empiric plasmaphresis was life saving.
CASE PRESENTATION: 67-year-old female with stage 1 adenocarcinoma of the breast presented with nausea, vomiting, diarrhea and neutropenic fever. She was treated with broad-spectrum antibiotics and supportive care. On day number 8 of hospitalization, patient developed altered mental status, acute kidney injury, anemia and thrombocytopenia. Patient had moderate elevation of lactate dehydrogenase and less than 1/hpf of schistocytes. There was no other evidence of MAHA. Patient subsequently developed status epilepticus requiring intubation. Patient’s body fluid cultures, cerebrospinal fluid analysis, vasculitis panel and imaging were all unremarkable. Based on her clinical picture, the diagnosis of atypical TTP was made and she was empirically started on plasmaphereis. The diagnosis was later confirmed by reduced plasma von-Willebrand factor (VWF)-cleaving metalloprotease (ADAMTS13), dramatic improvement in her mental status and platelet count in response to plasmaphresis. Patient was successfully extubated and subsequently discharged home.
DISCUSSION: Initially the diagnostic pentad was required to make the diagnosis of TTP, however later in a large series, (Sarode et al, Am J Hemtol 1997) MAHA and thrombocytopenia was noted in 100% of TTP patients followed by neurological involvement in 90%, renal involvement in 50%, and fever in 25% of the patients. In current clinical practice, thrombocytopenia and MAHA are sufficient to suggest TTP. Our patient had unexplained thrombocytopenia, fever, renal failure, neurological involvement and decreased ADAMTS13 in the absence of MAHA which is considered characteristic for diagnosing TTP. However, there have been few cases of TTP reported with appearance of MAHA late in the disease course (Sarode, J of Clinical Aphresis, 2009). Early diagnosis and empiric plasmapheresis has lead to dramatic improvement in survival, whereas delay in plasmapheresis is associated with poor outcome. Deficiency of ADAMTS13 leads to the accumulation of unusually large VWF multimers, promoting microvascular thrombi of platelets in the brain and kidneys leading to neurological and renal impairment. Plasmapheresis results in the removal of unusually large VWF multimers.
CONCLUSIONS: Clinicians should be aware of the unusual and atypical presentations of TTP so the diagnosis can be made in a timely fashion without delaying plasmapheresis, a life saving therapy for TTP.
Reference #1 Sarode R. "Atypical presentations of thrombotic thrombocytopenic purpura: a review." J Clin Apher. 2009;24(1):47-52.
Reference #2 James N. George, M.D "Thrombotic Thrombocytopenic Purpura" N Engl J Med 2006; 354:1927-1935
DISCLOSURE: The following authors have nothing to disclose: Riffat Meraj, Peter Lenz
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