What is the treatment approach for an adult patient with Evan syndrome, a history of autoimmune disorders, and symptoms such as fatigue, weakness, and easy bleeding or bruising?

Treatment Approach for Evans Syndrome in Adults

First-Line Treatment: Aggressive Corticosteroid Therapy

Initiate prednisone 1-2 mg/kg/day orally immediately, continuing until platelet count reaches 30-50 × 10⁹/L, typically over 2-4 weeks, then taper over 4-6 weeks to the lowest effective dose. 1, 2, 3

Evans syndrome requires more aggressive treatment than isolated autoimmune cytopenias due to higher relapse rates, increased thrombotic and infectious complications, and potentially fatal outcomes. 1 The clinical course is severe with high relapse rates, making early aggressive intervention critical. 2, 4

When to Add IVIG

• Add intravenous immunoglobulin (IVIG) 1 g/kg as a one-time dose when rapid platelet increase is required, particularly with severe bleeding or platelet count <25,000/μL. 1, 2
• IVIG combined with corticosteroids provides faster response in life-threatening presentations. 1

Essential Diagnostic Workup Before Treatment

Complete the following tests to guide therapy and identify secondary causes:

• Complete blood count with differential, peripheral blood smear (looking for spherocytes and polychromasia), and reticulocyte count 1, 2
• Direct antiglobulin test (DAT) to confirm autoimmune hemolytic anemia component 1, 2
• Bone marrow examination is strongly recommended to evaluate for lymphoproliferative disorders, myelodysplastic syndromes, or aplastic anemia 2, 4
• Screen for infections: HIV, hepatitis B virus, hepatitis C virus, CMV, and Helicobacter pylori 5, 1, 6
• Evaluate for lymphoproliferative disorders, systemic lupus erythematosus, and antiphospholipid syndrome 2, 6
• CT scan to assess for underlying malignancy 4

Second-Line Treatment: Rituximab

Rituximab is strongly recommended as second-line treatment in specific scenarios:

• Cold-type autoimmune hemolytic anemia (AIHA) - use rituximab as first-line treatment 1, 4
• Warm-type AIHA with antiphospholipid antibodies or previous thrombotic events 1, 4
• Chronic ITP component refractory to corticosteroids 1, 4
• Associated lymphoproliferative disorders - consider rituximab plus bendamustine 4

Avoid rituximab in patients with immunodeficiency or severe infections. 4

Chronic ITP Component Management

For chronic immune thrombocytopenia persisting beyond initial treatment, use thrombopoietin receptor agonists:

• Eltrombopag: 70-81% response rate 1, 2
• Romiplostim: 79-88% response rate 1, 2
• Particularly recommended for patients with previous grade 4 infections 4

Treatment for Secondary Evans Syndrome

HIV-Associated

Initiate antiretroviral therapy before other treatments, unless significant bleeding is present. 1

HCV-Associated

Consider antiviral therapy with close monitoring of platelet counts, as interferon-based regimens may worsen thrombocytopenia. 1

H. pylori-Associated

Administer eradication therapy. 1

Third-Line and Beyond

For refractory cases after corticosteroids and rituximab failure:

• Fostamatinib as third-line treatment 4
• Immunosuppressive agents (cyclosporine, azathioprine, cyclophosphamide) moved to third-line or further 4, 7
• Splenectomy is discouraged due to limited response (median duration only 1 month) and increased infection risk 4, 7

Supportive Care and Monitoring

Adjunctive Therapies

• Recombinant erythropoietin for AIHA with inadequate reticulocyte counts 4
• Sutimlimab (complement inhibitor) for relapsed cold AIHA 4

Thrombotic Risk Management

Evans syndrome carries increased thrombotic risk, including acute coronary syndrome. 8 Monitor for chest pain, and consider thromboprophylaxis in high-risk patients. 4 Dual antiplatelet therapy may be required if coronary intervention is needed, creating management challenges with thrombocytopenia. 8

Transfusion Guidelines

• All blood products should be irradiated and filtered 5
• Transfuse red blood cells and platelets according to local guidelines and clinical bleeding 5, 4

Response Monitoring

Evaluate response based on:

• Platelet count >30 × 10⁹/L with at least 2-fold increase from baseline 1
• Resolution of hemolysis: improved hemoglobin, decreased reticulocyte count, normalized bilirubin, and decreased LDH 1

Critical Pitfalls to Avoid

• Do not treat Evans syndrome like isolated ITP or AIHA - it requires more aggressive therapy from the outset 1, 4
• Do not perform splenectomy early - responses are brief and infection risk is high 4, 7
• Do not miss secondary causes - 25% have associated lymphoproliferative disorders, autoimmune diseases, or immunodeficiencies 9
• Do not ignore thrombotic risk - maintain high suspicion for thrombotic complications including cardiac events 4, 8