Prevention and treatment of venous thromboembolism--International Consensus Statement.

The aim of this document is to provide a clear and concise account of the evidence regarding efficacy or harm for various methods available to prevent and manage venous thromboembolism (VTE).

The influence of maternal Lewis, Secretor and ABO(H) blood groups on fetal growth restriction.

BACKGROUND: Fetal growth restriction (FGR) is associated with thrombosis of the placenta and an increased risk of subsequent vascular disease in the mother and fetus. The products of interactions between ABO(H), Lewis and Secretor genes are also associated with thrombosis and vascular disease risk. OBJECTIVES/METHODS: A prospective case-control study of mothers with a severe FGR pregnancy (cases, n = 128; controls, n = 288) was performed to determine whether FGR is associated with particular maternal blood groups. RESULTS: No association with ABO(H) status was observed, but FGR was more common in maternal secretors (odds ratio [OR] 1.70, 95% confidence interval [CI] 1.08-2.69) and consequently in those mothers expressing Le(b) on their red cells (OR 1.80, 95% CI 1.15-2.83), with a reduced risk in non-secretors and those expressing Le(a). Given the association between blood groups and both activated protein C resistance (APCR) and von Willebrand factor (VWF) levels, post hoc pilot studies on first-trimester APCR and VWF antigen levels and blood group genotypes were performed. No relationship with Lewis or Secretor was observed. Despite this, lower first-trimester VWF levels were observed in pregnancies subsequently complicated by FGR. CONCLUSIONS: This is the first study reporting a relationship between maternal Secretor/Lewis status and FGR. A link between blood groups and FGR is plausible, as both are associated with cardiovascular disease. We observed no relationship between Lewis/Secretor status and VWF or APCR, but this should be confirmed in a larger study. Thus, the mechanism whereby Secretor and/or Lewis influences FGR is unknown.

Antithrombotic treatment for recurrent pregnancy loss?

BACKGROUND: Recurrent pregnancy loss (RPL) is a major issue for women's health. Acquired and heritable thrombophilias are associated with RPL, this association could reflect a general prothrombotic phenotype rather than a specific thrombophilia. Antithrombotic intervention has therefore been assessed for RPL. RESULTS: Two large randomised trials with untreated control groups showed no benefit from antithrombotic treatment with LMWH and low dose aspirin in women with RPL. These trials had insufficient power to exclude an effect in women with underlying thrombophilia, ≥ 3 losses, or late losses. CONCLUSIONS: Antithrombotic intervention should not be recommended for unexplained RPL in general. There may be specific groups such as those with an heritable thrombophilia, or with three or more losses, or second trimester losses that might benefit and where further trials are required. Further there is a need to consider the benefits of LMWH on implantation such as in women undergoing assisted conception therapy.

Fetal corticotrophin-releasing hormone mRNA, but not phosphatidylserine-exposing microparticles, in maternal plasma are associated with factor VII activity in pre-eclampsia.

BACKGROUND: Pre-eclampsia is associated with increased placental debris circulating in maternal plasma. OBJECTIVES: This study related placental debris to maternal markers of coagulation and endothelial activation in pre-eclampsia. PATIENTS/METHODS: Circulating fetal corticotrophin-releasing hormone (CRH) mRNA and phosphatidylserine (PS)-exposing microparticles were assayed in third trimester plasma from women with pre-eclampsia (n = 32) and controls (n = 32) matched for age, body mass index, parity, and gestational age at sampling. Markers of maternal hemostasis and endothelial function were assessed. RESULTS: Fetal CRH mRNA levels were higher in pre-eclampsia [mean 0.75 (SD 2.77) CRH/glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA ratio] than in control pregnancies [0.20 (0.74), P = 0.014]. PS-exposing microparticle levels were not different between the groups. Women with pre-eclampsia had higher levels of tissue factor pathway inhibitor (TFPI), prothrombin F(1+2) fragment (F(1+2)), factor XIIa, soluble vascular cell adhesion molecule 1, von Willebrand factor and plasminogen activator inhibitor 1 than controls. Fetal CRH mRNA correlated with TFPI in pre-eclampsia and control groups (r = 0.38, P = 0.031, and r = 0.37, P = 0.039, respectively). Fetal CRH mRNA correlated with FVII activity (r = 0.43, P = 0.017) and PS-exposing microparticles correlated inversely with F(1+2) (r = -0.64, P < 0.001) in pre-eclampsia. CONCLUSIONS: Placental debris, assessed by fetal CRH mRNA levels in maternal blood, is related to coagulation potential, i.e. FVII activity, but not to markers of coagulation or endothelial activation in pre-eclampsia.

The parturient with coronary heart disease.

Cardiac disease is one of the leading indirect causes of maternal mortality in the UK, exceeding numbers of direct deaths from thromboembolism and hypertension combined. Over one year in our unit we managed six women with coronary heart disease. In this series five women had stable coronary heart disease. Three delivered electively by caesarean section under combined spinal-epidural anaesthesia, a further two women had spontaneous vaginal deliveries, one planned under epidural analgesia, the second unplanned after a rapid labour. The sixth woman had unstable angina requiring percutaneous coronary intervention in the 28th week of pregnancy and went on to deliver by caesarean section under general anaesthesia. Regional anaesthesia was avoided in this case because of antiplatelet and anticoagulant medication. There is a lack of level-one evidence to direct the management of these women. Clinical decisions were directed by guidelines for the perioperative management of patients with cardiac disease in non-cardiac surgery and the management of all cardiac disease in the obstetric population. A multi-disciplinary approach was taken, with a collaborative plan made for each pregnancy and delivery. A thorough clinical history and examination together with transthoracic echocardiography allows risk stratification of women with coronary heart disease at risk of peripartum cardiac events. Further investigation specific to each woman's management can then be undertaken.

Social inequalities in preterm birth in Scotland 1980-2003: findings from an area-based measure of deprivation.

OBJECTIVE: The preterm birth rate in Scotland has been increasing in recent years. Although preterm birth rates show a social gradient, it is unclear how this gradient has been affected by the overall increase. We examined time trends in singleton live preterm birth rates in relation to area-based socio-economic indicators. DESIGN: Population-based retrospective cohort study. SETTING: Scotland. PARTICIPANTS: All singleton live births delivered in Scottish hospitals between 1980 and 2003 (n= 1 423 993). MAIN OUTCOME MEASURES: Singleton live preterm birth rates in each deprivation quintile were derived. Subgroup analyses of those born moderately preterm (32-36 weeks), very preterm (28-31 weeks) and extremely preterm (24-27 weeks) were performed. RESULTS: The rate of singleton live preterm births increased from 49.7 per 1000 live births in the 5-year period 1980-84 to 56.1 per 1000 in the 4-year period 2000-03, a relative increase of 12.9%. A marked social gradient was apparent at all time periods: relative indices of inequality were 1.63 (95% CI 1.38-1.92) in 1980-84 and 1.55 (1.44-1.66) in 2000-03. Similar social gradients existed for all gestational age subgroups. Smoking status at first antenatal contact and increased obstetric intervention, possibly reflecting improvements in fetal monitoring and neonatal care, appeared to explain some but not all the social gradient. CONCLUSIONS: Social inequalities in preterm birth were apparent in Scotland between 1980 and 2003. In addition to helping pregnant women to stop smoking, other means to reduce social inequalities are required.

Gestational related changes in the deep venous system of the lower limb on light reflection rheography in pregnancy and the puerperium.

OBJECTIVE: To assess whether light reflection rheography testing is affected by the changes that occur in the deep venous system of the lower limb in pregnancy and the puerperium. METHODS: Twenty five women with a singleton pregnancy were recruited to undergo duplex Doppler ultrasound examinations of the common femoral vein to measure the vessel diameter and the blood flow velocity. Light reflection rheography testing was subsequently performed and the rate of venous emptying in the lower limb calculated. Serial measurements using both techniques were made at 15, 28, 36 weeks, and term gestation and at 2 days and 6 weeks postpartum. RESULTS: Duplex Doppler ultrasound confirmed that there is progressive dilatation of the deep venous system in pregnancy, which reaches a maximum at term and reverses after delivery. There is an accompanying reduction in blood flow velocity, which reaches a nadir at term and increases after delivery. The rate of venous emptying as measured by light reflection rheography decreases with increasing gestation, but did not fall to a level consistent with venous occlusion by a deep venous thrombosis. CONCLUSIONS: Light reflection rheography has been shown to provide reliable results in pregnancy and the puerperium. Therefore, it is a potential tool for screening for deep venous thrombosis in this population.