TY - JOUR
T1 - Platelet-bound C4d, low C3 and lupus anticoagulant associate with thrombosis in SLE
AU - Petri, Michelle A.
AU - Conklin, John
AU - O'Malley, Tyler
AU - Dervieux, Thierry
N1 - Funding Information:
Funding The study is funded by Exagen. The Hopkins Lupus cohort is supported by NIH grants R01 AR43727 and AR69572.
Publisher Copyright:
© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
PY - 2019/3/1
Y1 - 2019/3/1
N2 - 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.
AB - 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.
KW - complement
KW - lupus anti-coagulant
KW - systemic lupus erythematosus
KW - thrombosis
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U2 - 10.1136/lupus-2019-000318
DO - 10.1136/lupus-2019-000318
M3 - Article
C2 - 31168401
AN - SCOPUS:85063673402
SN - 2053-8790
VL - 6
JO - Lupus Science and Medicine
JF - Lupus Science and Medicine
IS - 1
M1 - 000318
ER -