Does Antiphospholipid Syndrome Cause Autoimmune Hemolytic Anemia?
Yes, antiphospholipid syndrome (APS) is associated with autoimmune hemolytic anemia (AIHA), occurring in approximately 10-12% of APS patients, though AIHA is not a diagnostic criterion for APS. 1, 2
Clinical Association and Prevalence
AIHA occurs as a recognized hematological manifestation of APS, though it falls outside the formal classification criteria which focus on thrombotic and obstetric complications. 3 In a multicenter study of 308 APS patients, AIHA was documented in 10.4% of cases. 1 A more recent Chinese cohort found AIHA in 11.7% (37/315) of APS patients. 2
Risk Factors and Clinical Patterns
APS patients who develop AIHA demonstrate specific risk patterns:
Secondary APS (associated with SLE) carries significantly higher AIHA risk compared to primary APS, with 62.2% of APS-AIHA patients having underlying SLE versus only 19.4% in APS patients without AIHA. 2
Independent risk factors for AIHA in APS include:
Clinical Implications and Associated Manifestations
When AIHA occurs in APS, it signals higher risk for specific complications:
- Cardiac valvular vegetations and thickening (P<0.0001) 1
- Arterial thrombosis (P<0.02) 1
- CNS manifestations including epilepsy (P<0.02) and chorea (P<0.03) 1
- Triple antiphospholipid antibody positivity (lupus anticoagulant, anticardiolipin, and anti-β2 glycoprotein I) 2
The presence of AIHA in APS patients more frequently correlates with arthralgias, arthritis, livedo reticularis, epilepsy, glomerular thrombosis, and myocardial infarction. 4
Diagnostic Approach
In patients presenting with AIHA, consider APS screening when:
- Unexplained thrombotic events occur alongside hemolysis 5
- Livedo reticularis, thrombocytopenia, or hypocomplementemia are present 1, 2
- There is concurrent SLE or other autoimmune disease 2, 4
AIHA may be the initial presenting manifestation of APS or occur simultaneously with APS diagnosis, with a median time interval of 12 months between APS onset and diagnosis. 2 In rare cases, AIHA may be the only apparent manifestation before life-threatening thrombotic complications emerge. 5
Clinical Pitfalls
Critical caveat: AIHA can mask underlying APS when thrombotic manifestations are absent initially. 5 Patients with apparently idiopathic AIHA warrant comprehensive thrombophilia screening including antiphospholipid antibody profiles, as thrombotic events may develop subsequently. 2, 5
The occurrence of AIHA in APS may define a subgroup at significant risk for subsequent development of SLE. 1 Therefore, patients with APS and AIHA require investigation for cardiac valvular disease, arterial thrombosis risk, and neurological complications even in the absence of typical APS thrombotic history. 1