What is Evans syndrome?

What is Evans Syndrome

Evans syndrome is a rare autoimmune disorder characterized by the simultaneous or sequential occurrence of immune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA) with a positive direct antiglobulin test (DAT), and occasionally autoimmune neutropenia. 1

Definition and Core Features

• Evans syndrome represents approximately 5-10% of all warm autoimmune hemolytic anemia cases and 2-5% of all ITP cases in adults 2
• The condition requires both immune-mediated platelet destruction (typically platelet count <100,000/μL) and hemolytic anemia with elevated reticulocyte count, elevated indirect bilirubin, decreased haptoglobin, and positive DAT 1
• The cytopenias can occur simultaneously or sequentially, and autoimmune neutropenia may also be present 1, 3

Classification: Primary vs Secondary

• Primary (idiopathic) Evans syndrome occurs without an identifiable underlying cause, while secondary Evans syndrome is associated with other conditions 1
• Secondary causes include:
  • Lymphoproliferative disorders 1
  • Systemic lupus erythematosus 1
  • Other autoimmune diseases 4
  • Primary immunodeficiencies (particularly common variable immune deficiency) 1, 5
  • Infections (HIV, hepatitis C, hepatitis B, CMV, Helicobacter pylori) 6
• In adult patients, approximately 21% have secondary Evans syndrome, mainly associated with other autoimmune diseases and hematologic malignancies 4

Clinical Course and Prognosis

• Evans syndrome has a severe clinical course with high relapse rates and potentially fatal complications 1, 4
• The condition requires more aggressive treatment than isolated autoimmune cytopenias due to higher relapse rates, increased risk of thrombotic complications, greater risk of infectious complications, and potentially fatal outcomes 6
• Bleeding occurs in approximately 42% of patients, mainly low grade and at ITP onset 4
• Infections and thrombotic complications occur in 33% and 21% of patients respectively, mainly grade ≥3, and correlate with the number of therapy lines 4
• Factors negatively affecting survival include advanced age, severe anemia at onset, disease recurrence, infections, and thrombosis 1, 4

Key Diagnostic Pitfalls

• When AIHA and ITP occur concomitantly, other differential diagnoses must be ruled out before confirming Evans syndrome 2, 3
• Critical exclusions include:
  • Thrombotic microangiopathies 3
  • Anemia due to bleeding complicating ITP 3
  • Vitamin deficiencies 3
  • Myelodysplastic syndromes 3
  • Paroxysmal nocturnal hemoglobinuria 3
  • HELLP syndrome when occurring during pregnancy 3

Relapsing Nature

• A remarkable number of relapses occur, requiring ≥3 therapy lines in 54% of cases 4
• The mortality rate is high, exceeding that of isolated autoimmune cytopenias 3
• Despite continuous progress in management, the relapsing clinical course necessitates high clinical awareness, prompt therapy, and anti-infectious/anti-thrombotic prophylaxis 4