Postpartum Thrombotic Microangiopathy: Hemolysis, Elevated Liver Enzymes, and Low Platelets (HELLP), Thrombotic Thrombocytopenic Purpura, or Atypical Hemolytic Uremic Syndrome?

Introduction: Thrombotic thrombocytopenic purpura (TTP) is a medical emergency caused by hereditary or immune-mediated ADAMTS13 deficiency, leading to thrombotic microangiopathy (TMA). In pregnancy, immune TTP may be misdiagnosed as preeclampsia with severe features or HELLP syndrome. Hemolytic uremic syndrome (HUS) presents with microangiopathic hemolytic anemia, thrombocytopenia and acute kidney injury (AKI), typically due to Shiga toxin-producing E. coli (STEC). Complement-mediated TMA (CM-TMA) or atypical HUS (aHUS), results from complement dysregulation and is treated with eculizumab. Case Description: A 26-year-old G2P2 female with mosaic Turner syndrome and chronic hypertension in pregnancy presented after a normal vaginal delivery complicated by postpartum hemorrhage due to uterine atony and retained placenta. Initially was treated for disseminated intravascular coagulation, but she developed elevated blood pressure with findings of hemolysis, transaminitis, thrombocytopenia and non-oliguric AKI, raising concerns for HELLP syndrome or preeclampsia with severe features. Renal function worsened, with severe thrombocytopenia and hemolytic anemia with schistocytes. A PLASMIC score of 6, negative ANA, anti-dsDNA, normal C3 and C4 and a history of recent diarrhea broadened suspicion to TTP, HUS and aHUS, including CM-TMA. While awaiting ADAMTS13 activity and aHUS testing, she was started on prednisone, plasmapheresis (PLEX) and eculizumab. ADAMTS13 activity was 68%, ruling out TTP. Steroids and PLEX were discontinued, while eculizumab was continued pending aHUS testing results. Shiga toxin was negative, making typical STEC-HUS unlikely. An aHUS panel showed elevated Factor B and H, cBb and sC5b-9, confirming terminal complement activation and supporting a diagnosis of aHUS. Eculizumab was continued with improvement in creatinine levels. Discussion: During the postpartum period, distinguishing HELLP, preeclampsia with severe features, SLE flare, HUS and CM-TMA from TTP may be difficult due to similar clinical presentations and laboratory findings. Contrary to HELLP and preeclampsia with severe features, delivery does not resolve HUS, CM-TMA (aHUS), SLE flare or TTP. This necessitates timely diagnosis and urgent initiation of treatment in cases of high suspicion (e.g. high PLASMIC score for TTP or renal failure) without waiting for either ADAMTS13 or aHUS test results.