Case Presentation: A 24-year-old Caucasian female with a family history of multiple autoimmune disorders presented with 3 weeks of bruising, petechiae, fatigue, and outside labs that revealed significant anemia and thrombocytopenia. Admission workup showed Hgb 7.6, platelets (PLT) < 3,000, and elevated MCV. Further labs showed elevated LDH, indirect bilirubinemia, haptoglobin< 10, and positive DAT C3 and IgG, identifying warm autoimmune hemolytic anemia (wAIHA). Hematology was consulted, and she received three units of platelets. PLT dropped again the next day, but an additional one unit platelets had no effect. Further transfusions were held for platelets and PRBC, unless clinically indicated, given lack of therapeutic impact. Given her easy bruising, petechiae, and lab work, the patient was diagnosed with Evans syndrome (ES) consisting of wAIHA and immune thrombocytopenia (ITP). Extensive workup including ANA, ADAMST13, HIV, Hepatitis, B12, folate, peripheral smear, and flow cytometry ruled out infectious, autoimmune, and lymphoproliferative etiologies of ES. Prednisone 100 mg was initiated. She remained asymptomatic with no evidence of bleeding and labs demonstrating low but stable Hgb and PLT. On Hospital Day Five, PLT dropped to 5,000, requiring IV immunoglobulin (IVIG) 1g/kg. PLT increased to 51,000. On Hospital Day Seven, Hgb increased, prednisone was decreased to 80 mg, and she was discharged with a Hematology clinic follow-up. Post-discharge labs at two days and one-week revealed a further increase in Hgb and PLT.
Discussion: ES is a rare autoimmune disorder characterized as the concurrent or sequential occurrence of wAIHA and ITP and/or immune neutropenia. The mechanism of ES is undetermined but is diagnosed by ruling out other etiologies of hemolytic anemia with thrombocytopenia. ES is idiopathic or secondary to Systemic Lupus Erythematous, lymphoproliferative diseases, or infections. Given the rarity of ES (annual incidence 1.8/million person-years), there are limited clinical studies around treatment modalities. ES is difficult to treat with increased incidence of relapses, infections, thrombotic complications, and mortality (20-24%) versus isolated wAIHA or thrombocytopenia. Treatment is derived from wAIHA and ITP guidelines, including corticosteroids, Rituximab, IVIG, transfusions, splenectomy, or immunosuppressants. Corticosteroids are first line ES treatment with an initial response rate up to 80%. After days of high-dose corticosteroids, an asymptomatic but critically low PLT in this patient prompted IVIG treatment, producing a robust increase in PLT. Significant improvement in Hgb and PLT at follow-up indicate IVIG may be a beneficial treatment to boost corticosteroid response on initial presentation, especially in severe thrombocytopenia. Early platelet transfusion was ineffective. An adjunct treatment (Rituximab) was not necessary for this patient’s initial presentation given Hgb and PLT improvement.
Conclusions: ES is a rare autoimmune disorder consisting of wAIHA and ITP. There is no definitive treatment regimen for ES. Empirical management is derived from isolated wAIHA or ITP guidelines. Yet, ES is often refractory to treatments. Therefore, it is important to manage ES as one disorder versus two isolated conditions. Management of ES may require multiple modalities, notably corticosteroids and IVIG, based on patient response. The severity of presentation and long-term mortality risk of ES demands specific management guidelines.