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Anti-heparin platelet factor 4 antibodies in systemic lupus erythaematosus are associated with IgM antiphospholipid antibodies and the antiphospholipid syndrome
  1. D Alpert1,
  2. L A Mandl,
  3. D Erkan1,
  4. W Yin2,
  5. E I Peerschke2,
  6. J E Salmon1
  1. 1
    Department of Rheumatology, Hospital for Special Surgery, New York, USA
  2. 2
    Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, New York, USA
  1. D Alpert, Jersey Shore University Medical Center, 1945 State Route 33, Neptune, New Jersey 07753, USA; alperd01{at}


Objective: To investigate the prevalence and clinical correlates of anti-heparin platelet factor 4 antibodies (anti-HPF4) in systemic lupus erythaematosus (SLE) patients with and without antiphospholipid antibodies (aPL).

Methods: Sera and clinical data were obtained from the Hospital for Special Surgery Autoimmune Disease Registry for 78 aPL-positive and 91 aPL-negative SLE patients without heparin-induced thrombocytopenia (HIT). Controls were 90 blood donors of comparable age and sex. Sera were assayed for anti-HPF4, IgG/IgM antiphospholipid antibodies (APhL), and IgG/IgM anti-β2-glycoprotein 1 antibodies (anti-β2GP1). Serotonin release assays (SRAs) were performed for subjects with positive anti-HPF4.

Results: Positive anti-HPF4 was seen in 9% of aPL-positive SLE patients, 4% of aPL-negative SLE patients and 1% of controls (p = 0.026, aPL-positive SLE vs controls). Two of 12 subjects with positive anti-HPF4 had reactive SRAs. In SLE patients, anti-HPF4 significantly correlated with IgM APhL, IgM anti-β2GP1, and inversely with complement C4. In immunoabsorption experiments, there was partial cross-reactivity of IgM anti-HPF4 with IgM APhL, but not with IgM anti-β2GP1. SLE patients with positive anti-HPF4 had increased odds of the antiphospholipid syndrome (APS; odds ratio (OR) 4.5, p = 0.019), and APS with arterial thrombosis (OR 6.1, p = 0.007). In multivariate linear regression analyses, APS and IgM APhL were independently associated with anti-HPF4.

Conclusions: Anti-HPF4 is detectable in SLE patients with and without aPL in the absence of HIT, and is most prevalent in aPL-positive SLE patients. In this SLE cohort, anti-HPF4 correlates with IgM APhL, IgM anti-β2GP1 and inversely with C4, and is associated with manifestations of APS.

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  • Additional data are published online only at

  • Funding: This study was supported by the Mary Kirkland Center for Lupus Research (DA, JES) and the Barbara Volcker Center for Women and Rheumatic Disease (DE). LAM is supported by NIH K23 AR050607-01 and a Clinical Arthritis Investigator Award from the New York State and National Chapter of the Arthritis Foundation. WY is supported by a fellowship from the American Heart Association, Heritage Affiliate. EIP is supported by NIH NHLBI HL067211.

  • Competing interests: None.