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Changes in haemostasis during normal pregnancy: does homocysteine play a role in maintaining homeostasis?

Published online by Cambridge University Press:  05 March 2007

Valerie A. Holmes
Valerie A. Holmes*
Affiliation:
Northern Ireland Centre for Diet and Health (NICHE), University of Ulster, Coleraine, BT52 ISA, UK, and Haematology Department, Belfast City Hospital, Belfast, BT9 7AB, UK
*
Corresponding author: Dr Valerie Holmes, Present address: Department of Medicine, Queen's University Belfast, Mulhouse, Grosvenor Road, Belfast BT12 6BJ, UK, fax +44 2890 235900, [email protected]
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Abstract

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Homocysteine, derived from the demethylation of the ammo acid methionine, is either further catabolised by trans-sulfuration to cysteine or remethylated to methionine. Remethylation to methionine requires the cofactors, folate and vitamin B12. Folate is an effective homocysteine-lowering agent and, thus, homocysteine and folate status are inversely related. Hyperhomocysteinaemia is a strong independent risk factor for venous thromboembolism (VTE) and is associated with adverse pregnancy outcomes such as pre-eclampsia, placental abruption, early pregnancy loss and neural-tube defects. Pregnancy is a risk factor for VTE as a result of prothrombotic changes in levels of haemostatic factors. However, despite this hypercoagulable state, the incidence of pregnancy-associated VTE is relatively low. Hyperhomocysteinaemia is associated with abnormalities in markers of coagulation activation, and recent research suggests that folic acid supplementation, as well as lowering homocysteine, lowers markers of coagulation activation and increases levels of coagulation inhibitors. Tissue factor (TF) is the initiator of blood coagulation in vivo, and homocysteine induces TF expression in vitro. During pregnancy, monocyte TF expression is lower than that in the non-pregnant state, and this lowering of TF may act to counterbalance increases in coagulation activation. Furthermore, despite a high folate requirement, several studies have reported that homocysteine is lower in normal pregnancy than in the non-pregnant state. Although the exact mechanism of homocysteine lowering during pregnancy is unclear, one possible outcome of lower homocysteine may be the protection of women from pregnancy complications and VTE, and thus lower homocysteine may contribute to maintaining homeostasis in haemostasis.

Keywords

HomocysteineHaemostasisPregnancy
Type
Micronutrient Group Symposium on ‘Micronutrient supplementation: when and why?’
Information
Proceedings of the Nutrition Society , Volume 62 , Issue 2 , May 2003 , pp. 479 - 493
Copyright
Copyright © The Nutrition Society 2003

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