What are the diagnostic criteria and initial management for Evans syndrome?

Evans Syndrome: Diagnostic Criteria and Initial Management

Diagnostic Criteria

Evans syndrome is diagnosed by the simultaneous or sequential occurrence of immune thrombocytopenia (platelet count typically <100,000/μL) and autoimmune hemolytic anemia with a positive direct antiglobulin test (DAT), after excluding other known underlying etiologies. 1

Required Laboratory Evaluation

• Complete blood count with differential, peripheral blood smear, and reticulocyte count are mandatory first steps 1
• Direct antiglobulin test (DAT) must be positive to confirm the autoimmune hemolytic anemia component 2, 1
• Reticulocyte count should be elevated, confirming active hemolysis 2, 1
• Peripheral blood smear should demonstrate spherocytes, polychromasia, and reduced platelets 1
• Additional hemolysis markers: elevated indirect bilirubin and decreased haptoglobin 1

Bone Marrow Evaluation

• Bone marrow examination is strongly recommended to evaluate for underlying lymphoproliferative disorders, myelodysplastic syndromes, or aplastic anemia 1
• The bone marrow should demonstrate adequate megakaryocytes and erythroid hyperplasia in Evans syndrome 1
• This evaluation is particularly important if abnormalities in blood tests require further investigation for diagnosis 2

Screening for Underlying Conditions

All patients require comprehensive infectious and autoimmune workup:

• Infectious screening: HIV, hepatitis C virus, hepatitis B virus, CMV, and Helicobacter pylori 2
• Autoimmune evaluation: systemic lupus erythematosus and antiphospholipid syndrome 2
• Immunodeficiency screening: common variable immune deficiency and other primary immunodeficiencies 1
• Lymphoproliferative disorder evaluation through imaging (CT scan recommended) 3

Initial Management Algorithm

First-Line Treatment

Prednisone 1-2 mg/kg/day orally is the recommended first-line treatment, continued for 2-4 weeks until platelet count increases to 30-50 × 10⁹/L, then tapered over 4-6 weeks to the lowest effective dose. 2, 1

When to Add IVIG

• IVIG 1 g/kg should be added to prednisone when rapid platelet increase is required, particularly in cases of severe bleeding or platelet count <25,000/μL 1
• IVIG can be used in conjunction with corticosteroids when a more rapid increase in platelet count is needed 4, 2
• The dose may be repeated if necessary 4

Treatment Duration Considerations

Important caveat: Treatment durations and tapering schedules differ between the immune thrombocytopenia and autoimmune hemolytic anemia components 3. The corticosteroid taper should be individualized based on which cytopenia is more severe or life-threatening at presentation.

Monitoring Response

• Evaluate response based on platelet count improvement, with a goal of >30 × 10⁹/L and at least 2-fold increase from baseline 2
• Monitor for resolution of hemolysis: improved hemoglobin, decreased reticulocyte count, and normalized bilirubin 2
• Check CBC weekly during initial treatment phase 4

Second-Line Treatment Options

Rituximab Indications

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

• Cold-type AIHA (also recommended as first-line in this subtype) 1, 3
• Warm-type AIHA with antiphospholipid antibodies or previous thrombotic events 1, 3
• Associated lymphoproliferative diseases 3
• Chronic ITP component 1

Critical contraindications: Rituximab should be avoided in patients with immunodeficiency or severe infections 3

Thrombopoietin Receptor Agonists

• Eltrombopag and romiplostim are recommended for chronic ITP component, with response rates of 70-81% for eltrombopag and 79-88% for romiplostim 2, 1, 5
• Particularly indicated in cases with previous severe infections (grade 4 infection history) 5

Special Clinical Scenarios

Secondary Evans Syndrome Management

• HIV-associated: Antiretroviral therapy should be initiated before other treatments, unless significant bleeding is present 2
• HCV-associated: Consider antiviral therapy with close monitoring of platelet counts due to potential worsening with interferon-based regimens 2
• H. pylori-associated: Administer eradication therapy 2

Supportive Care Requirements

• Initiate Pneumocystis jirovecii pneumonia prophylaxis in patients on high-dose immunosuppression 4
• CMV screening should be performed, especially with grade 4 lymphopenia 4
• Consider thrombotic prophylaxis based on individual risk factors 3

Critical Pitfalls to Avoid

• Do not assume normal platelet size on automated counters in suspected cases—always examine a blood smear, as some patients may have concurrent immune thrombocytopenia that can alter platelet morphology 4
• Splenectomy is discouraged in Evans syndrome due to less frequent long-term remissions compared to uncomplicated ITP and increased infection risk, especially in patients with immunodeficiency 3, 6
• Re-evaluate the diagnosis before declaring treatment failure, as other etiologies may have been missed and true refractoriness must be distinguished from inadequate initial treatment 5
• Evans syndrome has a high relapse rate and chronic course—patients require long-term follow-up even after achieving remission 7, 6