What is the treatment for a patient with Evans syndrome, a rare autoimmune disorder characterized by anemia and thrombocytopenia?

Treatment of Evans Syndrome

First-Line Treatment

Corticosteroids are the definitive first-line treatment for Evans syndrome, with prednisone 1-2 mg/kg/day orally recommended until platelet count increases to 30-50 × 10⁹/L, followed by a gradual taper over 4-6 weeks. 1, 2, 3

• Treatment should continue for 2-4 weeks before initiating the taper to the lowest effective dose 1
• High-dose dexamethasone (40 mg/day for 4 days) represents an alternative corticosteroid regimen that can produce sustained responses in up to 50% of patients 3
• Prednisone is FDA-approved for both idiopathic thrombocytopenic purpura and acquired (autoimmune) hemolytic anemia, the two components of Evans syndrome 4

Adjunctive First-Line Therapy

Intravenous immunoglobulin (IVIg) should be added to corticosteroids when rapid platelet increase is required, particularly with severe bleeding or platelet count <25,000/μL. 1, 2, 3

• The recommended dose is 1 g/kg as a one-time dose, which may be repeated if necessary 1, 3
• IVIg is specifically indicated when more rapid platelet response is needed beyond what corticosteroids alone provide 1

Critical Clinical Context

Evans syndrome requires more aggressive treatment than isolated autoimmune cytopenias due to higher relapse rates (up to 73% require second-line therapy), increased thrombotic and infectious complications, and potentially fatal outcomes. 1, 5, 6

• Only 32% of patients achieve remission off treatment after mean follow-up of 4.8 years 6
• Mortality remains higher than isolated autoimmune cytopenias, with 24% mortality reported in one cohort 6
• The clinical course is characterized by frequent exacerbations and remissions throughout the patient's lifetime 7, 8

Second-Line Treatment Algorithm

Rituximab is the preferred second-line agent in specific clinical scenarios: 2, 5

• Cold-type AIHA component: Rituximab is strongly recommended as first-line treatment 2, 5
• Warm-type AIHA with antiphospholipid antibodies or previous thrombotic events: Rituximab is recommended as second-line 2, 5
• Chronic ITP component: Rituximab is recommended as second-line treatment 2
• Associated lymphoproliferative disorders: Rituximab plus bendamustine combination is recommended 5

Important contraindications: Rituximab should be avoided in patients with immunodeficiency or severe infections 5

Thrombopoietin receptor agonists (eltrombopag, romiplostim) are recommended for the chronic ITP component: 1, 2

• Response rates: 70-81% for eltrombopag and 79-88% for romiplostim 1, 2
• Particularly recommended in cases of previous grade 4 infection 5

Third-Line and Refractory Disease

For refractory cases, the treatment hierarchy is: 5, 7

• Fostamatinib: Recommended as third-line or further-line treatment; may be considered second-line for patients with previous thrombotic events 5
• Immunosuppressive agents (cyclosporine, mycophenolate mofetil, azathioprine): Now relegated to third-line or further-line treatment 5, 7
• Splenectomy: May be considered but produces long-term remissions less frequently than in uncomplicated ITP; discouraged in patients with immunodeficiency or severe infections 5, 7

Stem cell transplantation offers the only chance of long-term cure for very severe and refractory cases, with allogeneic SCT potentially superior to autologous SCT, though both carry significant morbidity and mortality risks. 7

Supportive and Adjunctive Therapies

Recombinant erythropoietin is recommended for AIHA when reticulocyte counts are inadequate 5

Sutimlimab (complement inhibitor) is recommended for relapsed cold AIHA 5

Thrombotic and antibiotic prophylaxis should be implemented according to consensus recommendations 5

Essential Diagnostic Workup Before Treatment

Before initiating therapy, complete the following evaluation: 1, 2, 3

• Complete blood count with differential, peripheral smear (demonstrating spherocytes, polychromasia, reduced platelets), and reticulocyte count 2, 3
• Direct antiglobulin test (DAT) to confirm autoimmune hemolytic anemia 1, 3
• Bone marrow examination is strongly recommended to exclude lymphoproliferative disorders, myelodysplastic syndromes, or aplastic anemia 2
• Screen for underlying conditions: HIV, HCV, HBV, CMV, H. pylori 1, 3
• Evaluate for lymphoproliferative disorders, systemic lupus erythematosus, antiphospholipid syndrome, and immunodeficiency syndromes (including common variable immune deficiency) 1, 2, 3

Treatment of Secondary Evans Syndrome

HIV-associated: Antiretroviral therapy is recommended before other treatments unless significant bleeding is present 1

HCV-associated: Consider antiviral therapy with close platelet monitoring due to potential worsening with interferon-based regimens 1

H. pylori-associated: Administer eradication therapy 1

Response Assessment

Monitor treatment response based on: 1, 3

• Platelet count improvement (goal >30 × 10⁹/L and at least 2-fold increase from baseline) 1, 3
• Resolution of hemolysis: improved hemoglobin, decreased reticulocyte count, normalized bilirubin 1, 3
• Absence of bleeding 3

Critical Pitfall

In elderly patients, the cardiovascular risk from AIHA-related complications appears higher than ITP-related bleeding risk, requiring careful monitoring and aggressive treatment of the hemolytic component. 6