Role of Platelet-Bound C4d (PC4d) in Predicting Risk of Future Thrombotic Events in Systemic Lupus Erythematosus.

Objective: Platelet-bound complement activation product C4d (PC4d) levels correlate with history of thrombosis in patients with systemic lupus erythematosus (SLE). The present study evaluated whether PC4d levels could assess risk of future thrombosis events.

Methods: PC4d level was measured by flow cytometry. Thromboses were confirmed by electronic medical record data review.

Results: The study included 418 patients. Nineteen events (13 arterial and 6 venous) occurred in 15 subjects in the 3 years post-PC4d level measurement. PC4d levels above the optimum cutoff of 13 mean fluorescence intensity (MFI) predicted future arterial thrombosis with a hazard ratio of 4.34 (95% confidence interval [95% CI] 1.03-18.3) (P = 0.046) and a diagnostic odds ratio (OR) of 4.30 (95% CI 1.19-15.54). Negative predictive value of PC4d level of ≤13 MFI for arterial thrombosis was 99% (95% CI 97-100%). Although a PC4d level of >13 MFI did not reach statistical significance for prediction of total thrombosis (arterial and venous) (diagnostics OR 2.50 [95% CI 0.88-7.06]; P = 0.08), it was associated with all thrombosis (n = 70 historic and future arterial and venous events in the 5 years pre- to 3 years post-PC4d level measurement) with an OR of 2.45 (95% CI 1.37-4.32; P = 0.0016). In addition, the negative predictive value of PC4d level of ≤13 MFI for all future thrombosis events was 97% (95% CI 95-99%).

Conclusions: A PC4d level of >13 MFI predicted future arterial thrombosis and was associated with all thrombosis. Patients with SLE presenting with a PC4d level of ≤13 MFI had high probability of not experiencing arterial or any thrombosis in the 3 years afterwards. Taken together, these findings indicate that PC4d levels may help predict the risk of future thrombosis events in SLE.