Thrombotic thrombocytopenic purpura with features of evans syndrome in a case of lupus vasculitis Free

Introduction: Thrombotic thrombocytopenic purpura (TTP), distinguished by severe ADAMTS13 deficiency, is an emergency requiring immediate plasma exchange (PLEX). Systemic lupus erythematosus (SLE) patients face unique thrombotic microangiopathy (TMA) risks (TTP, lupus vasculitis, catastrophic antiphospholipid syndrome, or complement-mediated hemolytic uremic syndrome) and frequent autoimmune cytopenia like Evans syndrome (autoimmune hemolytic anemia and immune thrombocytopenia). A critical diagnostic dilemma arises when SLE flares present with both Evans features (Coombs-positive hemolysis and thrombocytopenia) and TMA signs (schistocytes, organ injury), obscuring the diagnosis of TTP. This overlap risks catastrophic delay in initiating life-saving PLEX, the cornerstone of TTP treatment, as Evans syndrome mimics TTP's hematologic features. Therapeutic conflicts (e.g., platelet transfusions are contraindicated in TTP but may be necessary for Evans-related bleeding) further complicate management in this rare, high-stakes scenario. This case demonstrates the imperative for empiric PLEX despite Evans syndrome when high-risk TMA features exist, alongside combined immunomodulation with steroids and rituximab. Its novel documentation of cardiac microvascular involvement, histologic confirmation of dual injury (TTP and lupus vasculitis), and successful unified strategy provide vital insights for managing this complex, life-threatening overlap.

Case Presentation: A 42-year-old woman with SLE and prior history of Immune Thrombocytopenic Purpura (ITP) presented with a 1-week history of progressive dizziness, dyspnea, hematuria, fatigue, substernal chest pain, and arthralgias. Physical examination revealed hypertension, tachycardia, a maculopapular rash on her arms, petechiae on her chest and abdomen, and mild confusion.

Investigations confirmed a life-threatening TMA triad: profound thrombocytopenia (platelets 3,000/µL), microangiopathic hemolytic anemia (MAHA) (Hemoglobin 6.2 g/dL, schistocytes >5/hpf, LDH 2033 U/L, haptoglobin <10 mg/dL), and acute kidney injury (creatinine 1.8 mg/dL). A strongly positive direct Coombs test confirmed autoimmune hemolytic anemia (AIHA), establishing Evans syndrome alongside her ITP history. Additional findings included hypocomplementemia (C3 <40 mg/dL, C4 <8 mg/dL) and elevated troponin I (0.631 ng/mL), suggesting cardiac microvascular involvement.

Despite diagnostic uncertainty due to Evans syndrome features masking TTP, empiric therapy was initiated with high-dose methylprednisolone (500 mg daily), daily therapeutic PLEX, and rituximab (375 mg/m²). Rapid hematologic improvement followed, with platelets rising to 62,000/µL and LDH normalizing to 480 U/L within 5 days. Subsequent ADAMTS13 activity confirmed severe deficiency (<0.03%), establishing SLE-associated secondary TTP. Later, renal biopsy revealed lupus nephritis Class IV with vascular microthrombi.

Discussion:

This rare case demonstrates concurrent SLE-associated TTP and Evans syndrome. Coombs-positive hemolysis initially masked the TTP diagnosis, emphasizing that MAHA severity (profound thrombocytopenia, high LDH, schistocytes, multi-organ injury) mandates immediate empiric PLEX for suspected TTP, irrespective of Evans features. Cardiac microvascular involvement (troponin elevation) signaled TMA severity. The rapid response to combined PLEX (removing ADAMTS13 inhibitors), steroids, and rituximab (targeting B-cell-driven autoimmunity) underscores a unified therapeutic strategy effective against both TTP and Evans syndrome. Histology confirmed SLE vasculitis contributed to TMA. This case reinforces that PLEX must not be delayed in SLE patients with high-risk TMA features, even when Evans syndrome complicates the presentation.

Conclusion: SLE patients with concurrent Evans syndrome and acquired TTP present a diagnostic and therapeutic challenge. Early testing for ADAMTS-13 activity and initiating PLEX in a timely fashion is of utmost importance. Such patients often need combined immunomodulation with steroids and rituximab, targeting the underlying shared B-cell pathology. Refractory cases may respond to complement inhibition with eculizumab, underscoring the multifactorial pathogenesis involving both immune complex and complement-mediated injury. Further research into this enigmatic presentation is required to improve standards of care.