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Published on: November 1, 2015
Platelet-bound C4d, low C3 and lupus anticoagulant associate with thrombosis in SLE
Michelle A Petri1, John Conklin2, Tyler O'Malley2
1Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Insights
Platelet C4d (PC4d) and low complement C3 are significant risk factors for thrombosis in systemic lupus erythematosus (SLE). A composite risk score including PC4d, low C3, and lupus anticoagulant (LAC) effectively predicts thrombosis risk.
Area of Science:
- Rheumatology
- Immunology
- Hematology
Background:
- Low complement C3 and lupus anticoagulant (LAC) are established risk factors for thrombosis in systemic lupus erythematosus (SLE).
- Platelet C4d (PC4d) deposition and antiphosphatidyl serine/prothrombin (PS/PT) complex antibodies are investigated as potential thrombosis risk factors in SLE.
- This study evaluates the association between PC4d, anti-PS/PT antibodies, and thrombotic events in SLE patients.
Purpose of the Study:
- To assess the association between platelet C4d (PC4d) deposition and thrombosis in patients with SLE.
- To evaluate antiphosphatidyl serine/prothrombin (PS/PT) complex antibody as an alternative marker to LAC for thrombosis risk in SLE.
- To develop and validate a composite risk score for predicting thrombosis in SLE.
Main Methods:
- A cross-sectional analysis of 149 SLE patients (86% female, mean age 47) with or without recent thrombotic events.
- PC4d, C3, LAC, and anti-PS/PT IgG levels were measured using flow cytometry, immunoturbidimetry, dilute Russell's viper venom time, and immunoassay, respectively.
- Logistic regression analysis was employed to calculate odds ratios (OR) and 95% confidence intervals (CI) for thrombosis risk.
Main Results:
- Abnormal PC4d (OR=8.4), low C3 (OR=9.5), LAC (OR=5.4), and anti-PS/PT IgG (OR=3.4) were significantly associated with thrombosis (p<0.05).
- A composite risk score incorporating PC4d, low C3, and LAC showed a higher prevalence in patients with thrombosis (1.93±0.25) versus those without (0.81±0.06) (p<0.01).
- Each unit increase in the composite risk score increased thrombosis odds by 5.2 times (p<0.01), and a similar score using anti-PS/PT antibody also associated with thrombosis (p<0.01).
Conclusions:
- A composite risk score including PC4d, low C3, and LAC is associated with recent thrombosis in SLE patients.
- This composite score acknowledges the multifactorial nature of thrombosis in SLE.
- PC4d and anti-PS/PT antibodies represent valuable additions to thrombosis risk assessment in SLE.
Background:
Low C3 and lupus anticoagulant (LAC) are known risk factors for thrombosis in SLE. We evaluated the association between C4d products deposited on platelets (PC4d) and thrombosis in SLE. Antiphosphatidyl serine/prothrombin (PS/PT) complex antibody was also evaluated as an alternative to LAC.
Methods:
This was a cross-sectional analysis of 149 consented patients with SLE (mean age: 47±1 years, 86% female) classified with (n=16) or without (n=133) thrombotic events in the past 5 years. Abnormal PC4d (≥20 units) was measured using flow cytometry. LAC and C3 were measured using dilute Russell's viper venom time (>37 s) and immunoturbidimetry, respectively. Anti-PS/PT antibody status (IgG) was measured by immunoassay. Statistical analysis consisted of logistic regression and calculation of OR estimates with 95% CI.
Results:
Abnormal PC4d (OR=8.4, 95% CI 2.8 to 24.8), low C3 (OR=9.5, 95% CI 3.0 to 30.3), LAC (OR=5.4, 95% CI 1.3 to 22.3) and anti-PS/PT IgG (OR=3.4, 95% CI 1.2 to 9.7) status associated with thrombosis (p<0.05). Cumulatively, the presence of PC4d, low C3 and LAC abnormalities as a composite risk score was higher in the presence of thrombosis (1.93±0.25) than in its absence (0.81±0.06) (p<0.01). Each unit of this composite risk score yielded an OR of 5.2 (95% CI 2.5 to 10.7) to have thrombosis (p<0.01). The composite risk score with anti-PS/PT antibody status instead of LAC also associated with thrombosis (p<0.01).
Conclusion:
A composite risk score including PC4d, low C3 and LAC was associated with recent thrombosis and acknowledges the multifactorial nature of thrombosis in SLE.
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