期刊
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
卷 12, 期 11, 页码 1801-1809出版社
WILEY
DOI: 10.1111/jth.12722
关键词
activated proteinC resistance; antibodies; antiphospholipid syndrome; Protac; proteinC; venous thromboembolism
资金
- LUPUS UK
- Bayer Healthcare (Newbury, UK)
BackgroundAntiphospholipid antibodies may interfere with the anticoagulant activity of activated proteinC (APC) to induce acquired APC resistance (APCr). AimsTo investigate the frequency and characteristics of APCr by using recombinant human APC (rhAPC) and endogenous proteinC activation in antiphospholipid syndrome (APS). MethodsAPCr was assessed in APS and non-APS venous thromboembolism (VTE) patients on warfarin and normal controls with rhAPC or Protac by thrombin generation. IgG anti-proteinC and anti-proteinS antibodies and avidity were assessed by ELISA. ResultsAPS patients showed greater resistance to both rhAPC and Protac than non-APS patients and normal controls (median normalized endogenous thrombin potential inhibition): APS patients with rhAPC, 81.3% (95% confidence interval [CI]75.2-88.3%; non-APS patients with rhAPC, 97.7% (95%CI93.6-101.8%; APS patients with Protac, 66.0% (95%CI59.5-72.6%); and non-APS patients with Protac, 80.7 (95%CI74.2-87.2%). APS patients also had a higher frequency and higher levels of anti-proteinC antibodies, with 60% (15/25) high-avidity antibodies. High-avidity anti-proteinC antibodies were associated with greater APCr and with a severe thrombotic phenotype (defined as the development of recurrent VTE while patients were receiving therapeutic anticoagulation or both venous and arterial thrombosis). Twelve of 15 (80%) patients with high-avidity anti-proteinC antibodies were classified as APS categoryI. ConclusionThrombotic APS patients showed greater APCr to both rhAPC and activation of endogenous proteinC by Protac. High-avidity anti-proteinC antibodies, associated with greater APCr, may provide a marker for a severe thrombotic phenotype in APS. However, in patients with categoryI APS, it remains to be established whether anti-proteinC or anti-(2)-glycoproteinI antibodies are responsible for APCr.
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