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COMPLEMENT C3 AND C4 ARE ASSOCIATED WITH POSTNATAL VENOUS THROMBOSIS
Author(s): ,
Anders Erik Astrup Dahm
Affiliations:
Haematology,Akershus University Hospital,Lørenskog,Norway;Institute of Clinical Medicine,University of Oslo,Oslo,Norway
,
Anne Flem Jacobsen
Affiliations:
Obstetrics and Gynaecology,Oslo University Hospital,Oslo,Norway
,
Eva Marie Jacobsen
Affiliations:
Haematology,Oslo University Hospital,Oslo,Norway
,
Hilde Skuterud Wik
Affiliations:
Haematology,Oslo University Hospital,Oslo,Norway
Per Morten Sandset
Affiliations:
Institute of Clinical Medicine,University of Oslo,Oslo,Norway
(Abstract release date: 05/17/18) EHA Library. Dahm A. 06/16/18; 214540; S838
Assoc. Prof. Anders E. A. Dahm
Assoc. Prof. Anders E. A. Dahm
Contributions
Abstract

Abstract: S838

Type: Oral Presentation

Presentation during EHA23: On Saturday, June 16, 2018 from 11:45 - 12:00

Location: Room A9

Background
Venous thrombosis (VT) is one of the most serious complications to pregnancy in developed countries. The complement system is part of the innate immune system. It has been suggested that the complement system and the coagulation system cross-talks and that high levels of C3 is associated with VT in the general population.

Aims
To investigate if high levels of complement C3 or C4 were associated with pregnancy related VT.

Methods
We investigated women in the Norwegian VIP study which is a population based case-control study of VT in pregnancy or within 3 months post partum (cases, n=313) and women without pregnancy related VT (controls, n=353). Blood samples were taken 3-16 years after the index pregnancy. We first investigated determinants of C3 and C4 in the control women with univariate linear regression. We then calculated the odds ratio (OR) for pregnancy related VT with multiple logistic regression including adjustments for other risk factors for pregnancy related VT associated with C3 or C4.

Results
In the control women C3 and C4 were associated with BMI. Control women pregnant at blood sampling had higher C3 than non-pregnant women. Both C3 and C4 were associated with CRP;  the coagulation factors fibrinogen, factor VIII or factor IX; and with the coagulation inhibitors protein C, protein S, antithrombin, and free tissue factor pathway inhibitor. The strongest associations were seen between C3 and CRP (standardized regression coefficient beta 0.67), C3 and protein C (beta 0.49), C3 and free TFPI (beta 0.40), C3 and fibrinogen ( beta 0.56), C3 and factor IX (beta 0.56). The crude OR for pregnancy-related VT was 1.8 (95% confidence interval (CI) 1.1-3.0) for C3 above the 90th percentile and 2.0 (95% CI 1.2-3.2) for C4 above the 90th percentile. Further stratification in antenatal and postnatal VT showed that the OR for antenatal VT for C3 above the 90th percentile was 0.87 (95% CI 0.43 to 1.7), and for C4 above the 90th percentile it was 1.4 (95% CI 0.73-2.6). For postnatal VT, the OR for C3 above the 90th percentile was 3.0 (95% CI 1.8-5.0), and for C4 above the 90th percentile 2.6 (95% CI 1.5-4.6). Adjustment for CRP, BMI, protein S, fibrinogen, factor VIII or factor IX only changed the odds ratios marginally.

Conclusion
Complement C3 and C4 were associated with several coagulation factors and coagulation inhibitors. High levels of C3 and C4 were associated with postnatal, but not antenatal VT.

Session topic: 35. Thrombosis and vascular biology & translational Research

Keyword(s): Complement, Pregnancy, Venous thromboembolism

Abstract: S838

Type: Oral Presentation

Presentation during EHA23: On Saturday, June 16, 2018 from 11:45 - 12:00

Location: Room A9

Background
Venous thrombosis (VT) is one of the most serious complications to pregnancy in developed countries. The complement system is part of the innate immune system. It has been suggested that the complement system and the coagulation system cross-talks and that high levels of C3 is associated with VT in the general population.

Aims
To investigate if high levels of complement C3 or C4 were associated with pregnancy related VT.

Methods
We investigated women in the Norwegian VIP study which is a population based case-control study of VT in pregnancy or within 3 months post partum (cases, n=313) and women without pregnancy related VT (controls, n=353). Blood samples were taken 3-16 years after the index pregnancy. We first investigated determinants of C3 and C4 in the control women with univariate linear regression. We then calculated the odds ratio (OR) for pregnancy related VT with multiple logistic regression including adjustments for other risk factors for pregnancy related VT associated with C3 or C4.

Results
In the control women C3 and C4 were associated with BMI. Control women pregnant at blood sampling had higher C3 than non-pregnant women. Both C3 and C4 were associated with CRP;  the coagulation factors fibrinogen, factor VIII or factor IX; and with the coagulation inhibitors protein C, protein S, antithrombin, and free tissue factor pathway inhibitor. The strongest associations were seen between C3 and CRP (standardized regression coefficient beta 0.67), C3 and protein C (beta 0.49), C3 and free TFPI (beta 0.40), C3 and fibrinogen ( beta 0.56), C3 and factor IX (beta 0.56). The crude OR for pregnancy-related VT was 1.8 (95% confidence interval (CI) 1.1-3.0) for C3 above the 90th percentile and 2.0 (95% CI 1.2-3.2) for C4 above the 90th percentile. Further stratification in antenatal and postnatal VT showed that the OR for antenatal VT for C3 above the 90th percentile was 0.87 (95% CI 0.43 to 1.7), and for C4 above the 90th percentile it was 1.4 (95% CI 0.73-2.6). For postnatal VT, the OR for C3 above the 90th percentile was 3.0 (95% CI 1.8-5.0), and for C4 above the 90th percentile 2.6 (95% CI 1.5-4.6). Adjustment for CRP, BMI, protein S, fibrinogen, factor VIII or factor IX only changed the odds ratios marginally.

Conclusion
Complement C3 and C4 were associated with several coagulation factors and coagulation inhibitors. High levels of C3 and C4 were associated with postnatal, but not antenatal VT.

Session topic: 35. Thrombosis and vascular biology & translational Research

Keyword(s): Complement, Pregnancy, Venous thromboembolism

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