Thrombotic thrombocytopenic purpura (TTP) is a rare but life-threatening thrombotic microangiopathy (TMA) characterized by the classic pentad of microangiopathic hemolytic anemia, thrombocytopenia, neurological abnormalities, renal impairment, and fever, although the complete pentad is present in only a minority of patients. Primary, or immune-mediated, TTP is caused by severe deficiency of ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13), a metalloproteinase that cleaves ultra-large von Willebrand factor multimers, resulting from the presence of inhibitory autoantibodies. The resulting accumulation of ultra-large von Willebrand factor multimers promotes platelet aggregation and formation of platelet-rich microthrombi in small blood vessels, leading to thrombocytopenia, microangiopathic hemolytic anemia, and organ ischemia.
TTP is a medical emergency requiring urgent treatment with plasma exchange, which has dramatically reduced mortality from over 90% to approximately 10-20%. However, the clinical presentation of TTP overlaps significantly with other thrombotic microangiopathies, and distinguishing primary TTP from secondary TMA is critical for guiding appropriate management, as plasma exchange may not be beneficial and could even be harmful in certain secondary forms. Secondary thrombotic microangiopathies encompass a diverse group of conditions that can mimic primary TTP clinically, including drug-induced TMA, complement-mediated atypical hemolytic uremic syndrome, pregnancy-associated TMA, transplantation-associated TMA, malignancy-associated TMA, and infection-associated TMA. Among infectious causes, HIV has been well-documented as a trigger for TTP-like syndromes, particularly in the pre-antiretroviral therapy era. HIV-associated TMA typically presents with a clinically indistinguishable picture from primary TTP, including thrombocytopenia, microangiopathic hemolytic anemia, and organ dysfunction, despite the absence of severely reduced ADAMTS13 activity or detectable ADAMTS13 inhibitors.
The pathogenesis of HIV-associated TMA is thought to involve direct endothelial injury by the virus, immune dysregulation, cytokine-mediated platelet activation, and opportunistic infections, rather than autoimmune ADAMTS13 deficiency. These cases highlight the role of HIV as a great mimicker of TTP, and they demand the same level of clinical urgency while requiring a different therapeutic approach, with antiretroviral therapy serving as the cornerstone of management rather than plasma exchange. This case report describes a 45-year-old transgender woman who presented to the emergency department with a three-month history of abdominal and lumbar pain with recent worsening, accompanied by significant unintentional weight loss. Initial laboratory evaluation revealed severe anemia and thrombocytopenia, and further investigation demonstrated schistocytes on peripheral blood smear, markedly elevated lactate dehydrogenase, and indirect hyperbilirubinemia, all consistent with microangiopathic hemolytic anemia. The calculated PLASMIC score was high, indicating a strong pretest probability of severe ADAMTS13 deficiency, and plasma exchange was urgently initiated in accordance with standard emergency protocols for suspected TTP. However, subsequent ADAMTS13 activity testing revealed preserved enzyme activity, effectively excluding immune-mediated TTP and prompting a broader diagnostic workup. Abdominal-pelvic computed tomography revealed extensive lymphadenopathies, mild splenomegaly, and multiorgan effusions involving the pleural, pericardial, and peritoneal cavities, findings consistent with a systemic infectious or inflammatory process. Bone marrow aspiration and cytomorphologic examination revealed marked hypercellularity with erythroid and megakaryocytic hyperplasia, multilineage dysplasia, and an increased proportion of reactive polyclonal plasma cells. Flow cytometry demonstrated a profound inversion of the CD4/CD8 ratio (0.02), with a severely reduced CD4+ T-cell count of only 33 cells/µL, consistent with advanced systemic immunodeficiency.
These findings prompted targeted virological investigations, which revealed a previously unknown HIV infection with quantifiable plasma HIV-RNA levels of 44,600 copies/mL, confirming a diagnosis of acquired immunodeficiency syndrome (AIDS). In addition to HIV, the patient was found to have active co-infections with Epstein-Barr virus (EBV) and human herpesvirus 8 (HHV-8), both common opportunistic pathogens in advanced HIV disease. Given the concomitant HHV-8 viremia and extensive lymphadenopathies, a strong clinical suspicion of AIDS-related Kaposi's sarcoma was raised, which was subsequently confirmed by histopathological examination of a cervical lymph node excision, revealing spindle-cell proliferation positive for the endothelial marker CD31 and HHV-8 latent nuclear antigen-1 (LANA-1).
The previously observed imaging findings were retrospectively attributed to disseminated AIDS-related Kaposi's sarcoma involving thoracic and abdominal organs. Following the diagnosis, the patient was transferred to the Infectious Diseases Unit, where antiretroviral therapy was promptly initiated, along with comprehensive supportive care including transfusion therapy. However, despite appropriate management, the patient's condition progressively deteriorated, and the clinical course culminated in a fatal outcome on day 69 of hospitalization. The irreversible extent of immunosuppression and endothelial injury at the time of presentation was likely beyond the point of therapeutic reversibility, and the only realistic opportunity to alter the outcome would have been an earlier diagnosis of HIV, prior to the onset of irreversible systemic damage.
DOI
10.1007/s11684-026-1234-y