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Published on: September 5, 2016
Role of Platelet-Bound C4d (PC4d) in Predicting Risk of Future Thrombotic Events in Systemic Lupus Erythematosus
Yevgeniya Gartshteyn1, John Conklin2, Michelle A Petri3
1Columbia University, New York, New York.
Insights
Platelet-bound complement C4d (PC4d) levels can predict future arterial thrombosis in systemic lupus erythematosus (SLE) patients. A low PC4d level indicates a low risk of future arterial or any thrombosis.
Area of Science:
- Immunology
- Rheumatology
- Cardiovascular Medicine
Background:
- Systemic lupus erythematosus (SLE) is associated with an increased risk of thrombosis.
- Platelet-bound complement activation product C4d (PC4d) has been correlated with a history of thrombosis in SLE patients.
Purpose of the Study:
- To evaluate the predictive value of PC4d levels for future thrombotic events in patients with SLE.
- To determine if PC4d levels can serve as a biomarker for assessing thrombosis risk in SLE.
Main Methods:
- PC4d levels were quantified using flow cytometry.
- Thrombotic events were identified and confirmed through electronic medical record data review.
- A cohort of 418 SLE patients was followed for 3 years post-PC4d measurement.
Main Results:
- Elevated PC4d levels (>13 MFI) predicted future arterial thrombosis (HR 4.34, P=0.046) with a negative predictive value of 99% for arterial events.
- PC4d levels >13 MFI were associated with all thrombosis (OR 2.45, P=0.0016), with a 97% negative predictive value for any future thrombosis.
- A PC4d level ≤13 MFI indicated a low probability of experiencing arterial or any thrombosis within 3 years.
Conclusions:
- PC4d levels >13 MFI are predictive of future arterial thrombosis in SLE patients.
- PC4d levels may serve as a valuable tool for risk stratification of thrombotic events in SLE.
- Patients with low PC4d levels (<13 MFI) have a favorable prognosis regarding future thrombosis.
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.
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