Superficial vein thrombosis, thrombin generation and activated protein C resistance as predictors of thromboembolic events in lupus and antiphospholipid patients. A prospective cohort study

Abstract

Introduction: Predicting thrombosis in patients with systemic lupus erythematosus (SLE) and/or antiphospholipid antibodies (aPL) is still challenging. Our objective was to determine risk factors for thrombotic events including activated protein C (APC) resistance proven by a thrombin generation (TG) assay in patients with SLE and/or aPL.

Materials and methods: We performed a prospective cohort study in a French University Hospital and tertiary care center. Ninety-two consecutive patients with SLE and/or aPL without ongoing anticoagulant treatment were enrolled. The outcome was time to thrombotic event. We evaluated clinical and laboratory variables including APC sensitivity ratio (APCsr) determined by TG. An APCsr>90th percentile of a control population indicated APC resistance.

Results: Patients were followed-up for a median duration of 35 months (inter-quartile range: 26 to 62; 320 patient-years). Thrombosis during follow-up occurred in 18 patients. In univariate analysis, together with history of hypertension, superficial vein thrombosis (SVT) and arterial thrombosis, patients with both aPL and APC resistance had an increased risk for incident thromboembolic events (HR, 3.67 [95% confidence interval, 1.31 to 10.31]). In multivariate analysis, only history of hypertension (HR, 10.77 [95% confidence interval, 3.15 to 36.83]), SVT (HR, 7.45 [95% confidence interval, 2.25 to 24.66]) and arterial thrombosis (HR, 3.31 [95% confidence interval, 1.14 to 9.55]) remained independent risk factors.

Conclusions: History of thrombosis including seemingly benign SVT have a higher predictive value for incident thrombotic events in SLE or aPL patients than APC resistance proven by TG.

Keywords: ACR; APC; APCsr; APS; Activated Protein C resistance; American college of rheumatology; Antiphospholipid antibodies; CAT; CI; CT; DVT; ELISA; ETP; HR; IQR; ISTH; International Society on Thrombosis and Haemostasis; LR+; LR-; NPV; PPV; SLE; SVT; Superficial vein thrombosis; Systemic lupus erythematosus; TG; TIAs; Thrombin generation; VKAs; aPL; activated protein C; activated protein C sensitivity ratio; antiphospholipid antibodies; antiphospholipid syndrome; calibrated automated thrombography; computed tomography; confidence interval; deep vein thrombosis; endogenous thrombin potential; enzyme linked immunosorbent assays; glycoprotein I; hazard ratio; inter quartile range; negative likelihood ratio; negative predictive value; positive likelihood ratio; positive predictive value; superficial vein thrombosis; systemic lupus erythematosus; thrombin generation; thrombotic ischemic attacks; vitamin K antagonists; ß(2)GPI.