Heparin-dependent and -independent anti-platelet factor 4 autoantibodies in patients with systemic lupus erythematosus

Rheumatology (Oxford). 2012 Sep;51(9):1721-8. doi: 10.1093/rheumatology/kes145. Epub 2012 Jun 19.


Objective: Antibodies that recognize complexes formed by platelet factor 4 (PF4) and heparin are involved in the pathogenesis of heparin-induced thrombocytopenia (HIT). This study was undertaken to investigate the prevalence and clinical correlations of anti-PF4 autoantibodies in patients with SLE.

Methods: We studied 118 patients with SLE, 78 with primary immune thrombocytopenia (ITP), 27 with primary APS, 2 with HIT (as positive controls) and 47 healthy controls. Heparin-dependent and -independent anti-PF4 antibodies were measured with an ELISA. Antibody binding was confirmed to be heparin-dependent when inhibited by the presence of a high concentration of heparin. Pathogenic anti-PF4 antibody was assessed by serotonin-release assay.

Results: Heparin-dependent anti-PF4 antibodies were detected in 11 SLE (9%) and 2 primary ITP (3%) patients, but at much lower levels than in HIT patients. In serotonin-release assays, only the HIT sera induced platelet activation in vitro. Heparin-independent anti-PF4 antibodies were detected in 17 SLE patients (14%). There was no correlation between the levels of heparin-dependent and -independent anti-PF4 antibodies. Cross-reactivity between these two antibodies was not detectable by ELISA competitive assay. Heparin-dependent anti-PF4 antibodies were associated with thrombocytopenia and IgM aCLs (P = 0.007 for both comparisons), while heparin-independent anti-PF4 antibody levels were correlated with SLE disease activity index (P = 0.0005). None of the SLE patients with anti-PF4 antibodies had previous heparin exposure.

Conclusion: PF4 is an autoimmune target in SLE patients. Heparin-dependent and -independent anti-PF4 autoantibodies may be involved in different aspects of pathophysiology of SLE.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antiphospholipid Syndrome / complications
  • Antiphospholipid Syndrome / diagnosis
  • Antiphospholipid Syndrome / immunology*
  • Autoantibodies / blood*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Heparin / adverse effects*
  • Humans
  • Lupus Erythematosus, Systemic / complications
  • Lupus Erythematosus, Systemic / diagnosis
  • Lupus Erythematosus, Systemic / immunology*
  • Male
  • Platelet Factor 4 / immunology*
  • Severity of Illness Index
  • Thrombocytopenia / chemically induced
  • Thrombocytopenia / diagnosis
  • Thrombocytopenia / immunology*


  • Autoantibodies
  • Platelet Factor 4
  • Heparin