Antiphospholipid antibodies and the risk of autoimmune hemolytic anemia in patients with systemic lupus erythematosus: A systematic review and meta-analysis

Autoimmun Rev. 2022 Jan;21(1):102913. doi: 10.1016/j.autrev.2021.102913. Epub 2021 Aug 8.


Background: According to criteria for the classification of Systemic Lupus Erythematosus (SLE), autoimmune hemolytic anemia is one of the disease-defining hematologic disorders together with thrombocytopenia. Since the recognition of Antiphospholipid Syndrome (APS), hemolytic anemia was frequently reported but several studies yielded contradictory results on the association between antiphospholipid antibodies (aPL) and hemolytic anemia. Therefore, we evaluated the association of aPL and autoimmune hemolytic anemia in SLE patients by conducting a systematic review and meta-analysis of available literature.

Methods: MEDLINE, EMBASE, Cochrane Library, congress abstracts, and reference lists of eligible studies were searched from 1987 to 2020. Studies were selected if they included SLE patients with descriptions of exposure to aPL and occurrence of hemolytic anemia. Three reviewers extracted study characteristics and association data from published reports. Risk estimates were pooled using random effects models and sensitivity analyses. We followed the PRISMA guidelines for all stages of the meta-analysis (Supplemental Table). PROSPERO registration number: CRD42015027376.

Results: From 3555 articles identified, 38 studies met inclusion criteria and included 8286 SLE patients. 20.5% of aPL-positive SLE patients had hemolytic anemia compared to 8.7% in aPL-negative SLE patients. The overall pooled Odds Ratio (OR) for hemolytic anemia in aPL positive patients was 2.83 (95% CI; 2.12-3.79). Among aPL subtypes, the risk of hemolytic anemia was highest for lupus anticoagulant (OR = 3.37 [95% CI; 2.26-5.04]) and, antiβ2Glycoprotein I antibodies (OR = 3.21 [95% CI; 1.54-6.72]), especially IgM antiβ2Glycoprotein I (OR = 3.01 [95% CI; 1.26, 7.24]).

Conclusions: The occurrence of hemolytic anemia was strongly associated with presence of aPL in SLE patients. Interestingly, IgM isotypes indicate an increased risk of hemolytic anemia in SLE.

Keywords: Antiphospholipid antibodies; Antiphospholipid syndrome; Autoimmune hemolytic anemia; Systemic lupus erythematosus.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Anemia, Hemolytic, Autoimmune* / complications
  • Anemia, Hemolytic, Autoimmune* / epidemiology
  • Antibodies, Antiphospholipid
  • Antiphospholipid Syndrome*
  • Humans
  • Lupus Coagulation Inhibitor
  • Lupus Erythematosus, Systemic* / complications


  • Antibodies, Antiphospholipid
  • Lupus Coagulation Inhibitor