Changes in haemostasis during normal pregnancy: does homocysteine play a role in maintaining homeostasis?
Homocysteine, derived from the demethylation of the amino 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.
D005260:Female; D005492:Folic Acid / Q000097:blood; D006706:Homeostasis / Q000502:physiology*; D006710:Homocysteine / Q000502:physiology*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000097:blood / Q000150:complications*; D009436:Neural Tube Defects / Q000209:etiology; D010922:Placenta Diseases / Q000209:etiology; D011225:Pre-Eclampsia / Q000209:etiology; D011247:Pregnancy / Q000378:metabolism / Q000502:physiology*; D011250:Pregnancy Complications, Hematologic / Q000097:blood; D013923:Thromboembolism / Q000097:blood / Q000150:complications*
D006710:Homocysteine; D005492:Folic Acid