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Thromb Haemost 2019; 119(09): 1481-1488
DOI: 10.1055/s-0039-1692426
Stroke, Systemic or Venous Thromboembolism
Georg Thieme Verlag KG Stuttgart · New York

Elevated Complement C3 and C4 Levels are Associated with Postnatal Pregnancy-Related Venous Thrombosis

Anders E. A. Dahm
1   Department of Haematology, Akershus University Hospital, Lørenskog, Norway
2   Institute of Clinical Medicine, University of Oslo, Oslo, Norway
,
Eva Marie Jacobsen
3   Department of Haematology, Oslo University Hospital, Oslo, Norway
,
Hilde Skuterud Wik
3   Department of Haematology, Oslo University Hospital, Oslo, Norway
,
Anne Flem Jacobsen
2   Institute of Clinical Medicine, University of Oslo, Oslo, Norway
4   Department of Obstetrics and Gynaecology, Oslo University Hospital, Oslo, Norway
,
Tom Eirik Mollnes
5   Research Laboratory, Nordland Hospital Trust, Bodø, Norway
6   Department of Clinical Medicine, UiT–The Arctic University of Norway, Tromsø, Norway
7   K.G. Jebsen TREC, UiT–The Arctic University of Norway, Tromsø, Norway
8   Department of Immunology, Oslo University Hospital, Rikshospitalet, University of Oslo, Oslo, Norway
9   Centre of Molecular Inflammation Research, Norwegian University of Science and Technology, Trondheim, Norway
,
Sandip M. Kanse
10   Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
,
Per Morten Sandset
2   Institute of Clinical Medicine, University of Oslo, Oslo, Norway
3   Department of Haematology, Oslo University Hospital, Oslo, Norway
› Author Affiliations Funding This study was financially supported by grants from the Norwegian Research Council (grant no 160805-V50) and from the Eastern Health Authority Trust of Norway.
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Publication History

30 January 2019

24 April 2019

Publication Date:
29 June 2019 (online)

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Abstract

High levels of complement C3 are associated with venous thrombosis (VT) in the general population. We investigated if high C3 and C4 levels were associated with pregnancy-related VT. We undertook the Norwegian VIP study, a case–control study of VT in pregnancy or within 3 months postpartum (cases, n = 313) and women without pregnancy-related VT (controls, n = 353). Determinants of C3 and C4 in the control women were investigated with linear regression and the odds ratio (OR) for pregnancy-related VT was calculated with logistic regression. We found that levels of C3 and C4 were associated with body mass index (BMI), C-reactive protein (CRP); with the coagulation factors (F) fibrinogen, FVIII, and FIX; and with the coagulation inhibitors antithrombin, protein C, protein S, and tissue factor pathway inhibitor. These associations were influenced by CRP levels. 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. Stratification in antenatal and postnatal VT showed that C3 and C4 were only associated with postnatal VT with an OR for high C3 of 3.0 (95% CI, 1.8–5.0), and for high C4 of 2.6 (95% CI, 1.5–4.6). Adjustment for high FIX and BMI reduced the ORs. We conclude that the association between postnatal VT and C3 and C4 suggests that there is clinically relevant crosstalk between the complement and the coagulation system.

Keywords

venous thromboembolism - pregnancy - complement system proteins - blood coagulation - case–control studies

Authors' Contributions

A.D. did the statistics and wrote the first draft, A.F.J. collected the data and reviewed the manuscript, and P.M.S. designed the study and reviewed the manuscript. T.E.M. contributed intellectually with complement knowledge and interpretation of data. H.S.W., S.M.K., and E.M.J. edited the manuscript. All authors critically revised the manuscript and approved the final version.


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