Abstract
Thrombotic thrombocytopenic purpura (TTP) is a rare but life-threatening hematological emergency defined by severe ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13) deficiency. However, TTP-like syndromes without ADAMTS13 reduction can occur in systemic infections such as human immunodeficiency virus (HIV), posing significant diagnostic and therapeutic challenges, particularly in high-risk and underdiagnosed populations. We report the case of a 45-year-old transgender woman who presented to the emergency department with abdominal and lumbar pain, severe anemia, and thrombocytopenia. Laboratory tests revealed schistocytes, elevated lactate dehydrogenase (LDH), and indirect hyperbilirubinemia, prompting a high PLASMIC score and the initiation of plasma exchange for suspected TTP. Subsequent investigations revealed a preserved ADAMTS13 activity and uncovered a previously undiagnosed advanced HIV infection, along with Epstein-Barr virus (EBV) and human herpesvirus 8 (HHV-8) viremia. Despite timely initiation of antiretroviral therapy and comprehensive supportive care, the patient experienced progressive clinical deterioration and died during hospitalization. This case illustrates a multifactorial secondary thrombotic microangiopathy (TMA) mimicking primary TTP, triggered by advanced HIV and possibly exacerbated by estrogen-associated prothrombotic risk. It highlights the importance of early virologic screening and broad diagnostic reasoning in high-risk patients with overlapping prothrombotic conditions, where identifying the underlying cause of secondary TMA is critical to improving outcomes and preventing missed opportunities for life-saving intervention.