Clinical features and therapeutic plasma exchange in postpartum hemorrhage-associated thrombotic microangiopathy following massive transfusion

Abstract

Pregnancy-associated thrombotic microangiopathy (TMA) is a rare but life-threatening emergency, the diagnosis of which is particularly challenging when it emerges following postpartum hemorrhage (PPH), massive transfusion, disseminated intravascular coagulation (DIC), or HELLP (hemolysis, elevated liver enzymes, low platelets)-like laboratory abnormalities. We use two institutional cases to anchor recent literature and highlight bedside clues that should prompt suspicion of TMA after obstetric bleeding. In both patients, active hemorrhage was initially controlled, yet severe thrombocytopenia, Coombs-negative microangiopathic hemolytic anemia with schistocytes, markedly elevated lactate dehydrogenase (LDH), and renal dysfunction persisted or progressed. These features prompted the initiation of therapeutic plasma exchange (TPE), after which both patients showed clinical and biochemical improvement.

Recent literature from 2021 to 2025 reinforces three messages. First, postpartum TMA should be suspected when hematologic and renal abnormalities continue after hemostasis rather than resolving with routine obstetric care. Second, immune thrombotic thrombocytopenic purpura (TTP) must be promptly considered, as delayed treatment can be catastrophic; therefore, early empiric plasma-based therapy remains appropriate when TTP cannot be confidently excluded. Third, PPH-associated TMA is biologically heterogeneous, and some patients may ultimately prove to have complement-mediated disease rather than classic TTP, which has implications for complement evaluation, targeted short-term complement inhibition, and follow-up strategies.

We conclude that severe hemorrhage and transfusion support do not preclude the presence of TMA; in some patients they may obscure it. A pragmatic, multidisciplinary approach incorporating repeated blood-smear review, rapid hemolysis assessment, ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 motif, member 13) testing when available, complement assessment when clinically indicated, and timely initiation of TPE can improve early decision-making in this uncommon yet high-risk setting.