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Biomedical subjects

I A Greer

Publications and source records attributed to I A Greer.

At least 19 recordsLinked to original sources

Thrombophilia in pregnancy: a systematic review.

Growing evidence suggests that thrombophilia is associated with venous thromboembolism (VTE) and adverse pregnancy outcomes. However, methodological limitations have made it difficult to obtain a clear overview of the overall risks. We conducted a systematic review to determine the risk of VTE and adverse pregnancy outcomes associated with thrombophilia in pregnancy. The effectiveness of prophylactic interventions during pregnancy was also evaluated. Major electronic databases were searched, relevant data abstracted and study quality assessed by two independent reviewers. Odds ratios (ORs) stratified by thrombophilia type were calculated for each outcome. A total of 79 studies were included in our review. The risks for individual thrombophilic defects were determined for VTE (ORs, 0.74-34.40); early pregnancy loss (ORs, 1.40-6.25); late pregnancy loss (ORs, 1.31-20.09); pre-eclampsia (ORs, 1.37-3.49); placental abruption (ORs, 1.42-7.71) and intrauterine growth restriction (ORs, 1.24-2.92). Low-dose aspirin plus heparin was the most effective in preventing pregnancy loss in thrombophilic women (OR, 1.62). Our findings confirm that women with thrombophilia are at risk of developing VTE and complications in pregnancy. However, despite the increase in relative risk, the absolute risk of VTE and adverse outcomes remains low. There is also a lack of controlled trials of antithrombotic intervention to prevent pregnancy complications. Thus, at present, universal screening for thrombophilia in pregnancy cannot be justified clinically.

Female↗

Anaesthetic considerations in a parturient with critical coronary artery disease and a drug-eluting stent presenting for caesarean section.

A parturient presented with her first symptoms of coronary artery disease at 18 weeks' gestation. Following an angiogram, a drug-eluting stent was inserted, resulting in resolution of her symptoms. The patient was prescribed anti-platelet medication including clopidogrel. She was delivered by elective caesarean section at 35 weeks under general anaesthesia. The anaesthetic management is discussed and a review of the literature presented.

Adult↗

The role of factor V Leiden in maternal health and the outcome of pregnancy.

There is growing evidence that women with thrombophilia are at increased risk of pregnancy related venous thromboembolism and of adverse pregnancy outcome including pregnancy loss, pre-eclampsia, intrauterine growth retardation and placental abruption. The factor V Leiden mutation is a heritable thrombophilia present in 5-8% of Caucasian populations. In its heterozygous form it is associated with a 4-to 8-fold increase in thrombotic risk. Homozygous inheritance, however, confers around an 80-fold increase in relative risk of thrombosis. The relationship between factor V Leiden and adverse pregnancy outcome has been studied in the recent literature, however the size of the estimated risks varies between individual studies due to heterogeneity of study design and small sample size in many cases. The management of women with factor V Leiden in pregnancy with low molecular weight heparin has been shown to be both safe and effective in preventing venous thromboembolism and improving pregnancy loss. Large scale, randomised controlled studies are required to confirm these findings. Selective screening for factor V Leiden based on prior venous thromboembolism has been shown to be marginally more cost-effective than universal screening in pregnancy and a recent consensus statement has recommended screening for thrombophilia based on a strong personal or family history of venous thromboembolism. There is now some evidence that placental problems may be associated with factor V Leiden in the fetus. There has also been an observed association between maternal factor V Leiden and fetal or neonatal stroke. These areas require further study and at present there is no evidence-based approach to investigation, prevention or management.

Abortion, Habitual↗

Fetal cord plasma lipoprotein status in uncomplicated human pregnancies and in pregnancies complicated by pre-eclampsia and intrauterine growth restriction.

Maternal lipids have been studied extensively in pre-eclampsia (PE) and intrauterine growth restriction (IUGR) but little is known about fetal lipids. We hypothesised that the maternal lipid perturbations in PE and IUGR pregnancies would result in similar alterations in the fetal lipid profile. We performed a cross-sectional case control study of maternal and fetal (delivery venous cord blood) lipid and lipoprotein concentrations in third trimester uncomplicated pregnancies (n = 81) and in pregnancies complicated by PE (n = 23) or IUGR (n = 17). In uncomplicated pregnancies, fetal log total cholesterol (TC), log triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) levels were significantly affected by mode of delivery. Fetal log TC (r = 0.37, P = 0.02), log TG (r = 0.34, P = 0.04) and TC/HDL-C ratio (r = 0.31, P = 0.05) were positively correlated with placental weight. Maternal TC (r = 0.35, P = 0.03) and LDL levels (r = 0.36, P = 0.02) were associated with fetal HDL-C levels. Maternal TC was significantly elevated in PE [mean 6.75 (standard deviation 1.14) mmol/L] compared to BMI-matched controls [5.94 (0.89) mmol/L P = 0.04]. In PE, fetal log TC [mean 0.36 (0.23) versus 0.11 (0.15) log mmol/L, P = 0.03], fetal log TG [-0.21 (0.32) versus -0.49 (0.26) log mmol/L, P = 0.02] and fetal TC/HDL-C ratio [3.64 (1.62) versus 1.80 (0.86), P = 0.001] were higher than in controls, after adjustment for mode of delivery. In IUGR, fetal log TG [-0.17 (0.35) versus -0.57 (0.10) log mmol/L, P = 0.01] was higher than controls, after adjustment for mode of delivery. There were no correlations between maternal and fetal lipid levels, or between fetal birth weight and either maternal or fetal lipids in the PE or IUGR groups. We conclude that although fetal lipids do not show a direct correlation with maternal lipids in PE or IUGR, these complications of pregnancy significantly impact upon fetal lipid levels possibly due to increased fetal stress or compromised placental lipid transport. Our findings are potentially pertinent to understanding the future cardiovascular health of the offspring.

Adult↗

Low-molecular-weight heparin for the prevention and treatment of venous thromboembolism in pregnancy.

PURPOSE OF REVIEW: Low-molecular-weight heparins (LMWHs) have largely replaced unfractionated heparins for both prophylaxis and treatment of venous thromboembolism in nonpregnant patients. However, until recently, evidence in pregnant women was lacking, despite the increasing use of LMWHs during pregnancy in clinical practice. This review covers recent literature on the use of LMWHs in relation to pregnancy. RECENT FINDINGS: The main areas covered in this review are the use of LMWHs in both prophylaxis and treatment of venous thromboembolism in pregnancy. The review also considers issues relating to monitoring of LMWHs in pregnancy, and safety from both a maternal and a fetal perspective. SUMMARY: The available evidence demonstrates that LMWHs are of at least equivalent efficacy but have a better safety profile compared with unfractionated heparins in both prophylaxis and treatment of maternal venous thromboembolism, and are more convenient to administer. There is no consensus with respect to whether these agents require monitoring during pregnancy other than periodic checking of the platelet count. The clinical implication from the available evidence is that LMWHs should now be regarded as the anticoagulant agents of choice for both prophylaxis and treatment of maternal venous thromboembolism.

Factor Xa↗

Ketorolac, diclofenac, and ketoprofen are equally safe for pain relief after major surgery.

BACKGROUND: Ketorolac is approved for the relief of postoperative pain but concerns have been raised over a possible risk of serious adverse effects and death. Two regulatory reviews in Europe on the safety of ketorolac found the data were inconclusive and lacked comparison with other non-steroidal anti-inflammatory drugs. The aim of this study was to compare the risk of serious adverse effects with ketorolac vs diclofenac or ketoprofen in adult patients after elective major surgery. METHODS: This prospective, randomized multicentre trial evaluated the risks of death, increased surgical site bleeding, gastrointestinal bleeding, acute renal failure, and allergic reactions, with ketorolac vs diclofenac or ketoprofen administered according to their approved parenteral and oral dose and duration of treatment. Patients were followed for 30 days after surgery. RESULTS: A total of 11,245 patients completed the trial at 49 European hospitals. Of these, 5634 patients received ketorolac and 5611 patients received one of the comparators. 155 patients (1.38%) had a serious adverse outcome, with 19 deaths (0. 17%), 117 patients with surgical site bleeding (1.04%), 12 patients with allergic reactions (0.12%), 10 patients with acute renal failure (0.09%), and four patients with gastrointestinal bleeding (0.04%). There were no differences between ketorolac and ketoprofen or diclofenac. Postoperative anticoagulants increased the risk of surgical site bleeding equally with ketorolac (odds ratio=2.65, 95% CI=1.51-4.67) and the comparators (odds ratio=3.58, 95% CI=1.93-6.70). Other risk factors for serious adverse outcomes were age, ASA score, and some types of surgery (plastic/ear, nose and throat, gynaecology, and urology). CONCLUSION: We conclude that ketorolac is as safe as ketoprofen and diclofenac for the treatment of pain after major surgery.

Acute Kidney Injury↗

Low molecular weight heparin for the treatment of venous thromboembolism in pregnancy: a case series.

OBJECTIVES: To assess the use of low molecular weight heparin for the treatment of venous thromboembolism in pregnancy. DESIGN: A prospective observational study. SETTING: The maternity units in two university teaching hospitals and one district general teaching hospital. POPULATION: Thirty-six consecutive women presenting with objectively diagnosed venous thromboembolism during pregnancy and the immediate puerperium. METHODS: Treatment with the low molecular weight heparin enoxaparin, approximately 1 mg/kg s.c., twice daily, based on early pregnancy weight. MAIN OUTCOME MEASURES: Peak anti-Xa activity (three hours post-injection), alterations in treatment, side effects and the use of regional anaesthesia. RESULTS: In 33 women, the initial dose of enoxaparin provided satisfactory peak anti-Xa activity (median 0.8 u/mL, range 0.44-1.0 u/mL) and was continued. Three women required dose reduction since peak anti-Xa activities were above the therapeutic range (1.2, 1.2 and 1.1 u/mL). No woman developed thrombocytopaenia, haemorrhagic complication or further thromboembolic episode. Two women developed allergic skin reactions on enoxaparin and were changed to tinzaparin. Fifteen women had regional anaesthesia for delivery, with a reduced dose of enoxaparin (40 mg once daily), all without complication. CONCLUSIONS: Enoxaparin is a safe and effective treatment for venous thromboembolism during pregnancy and confers a major advantage over unfractionated heparin through its simplified regimen of administration.

Adult↗

Antenatal waist circumference and hypertension risk.

OBJECTIVE: To assess whether waist circumference at the first antenatal visit predicts risk of developing hypertension later in pregnancy. METHODS: Pregnant women with singleton pregnancies (n = 1142, median age 29 years, interquartile range 25-32 years, 387 primigravidas) were recruited at their first antenatal visits. Using standardized methods, midwives determined the weights, heights (for calculation of body mass index [BMI]), and waist circumferences of all women. Eighty-two women developed pregnancy-induced hypertension, and 21 developed preeclampsia (hypertension with proteinuria). RESULTS: The median waist circumference between 6 and 16 weeks' gestation was 79 cm (interquartile range 72-84 cm), and there was no significant relationship between waist circumference and gestational age. Greater waist circumference was noted in subjects who subsequently developed pregnancy-induced hypertension (median 81 versus 77 cm, Mann-Whitney U test, P =.002) or preeclampsia (median 80 versus 77 cm, P =.02). The conventional, nonpregnant waist circumference action level of 80 cm gave a Mantel-Haenszel odds ratio (OR) for pregnancy-induced hypertension of 1.8 (95% confidence interval [CI] 1.1, 2.9) and for preeclampsia of 2.7 (95% CI 1.1, 6.8), compared with waists of less than 80 cm. Body mass index values were higher in women who developed pregnancy-induced hypertension (median 26 versus 24, P =.001) or preeclampsia (median 26 versus 24, P =.02). The conventional action limit for a BMI of 25 had an OR for pregnancy-induced hypertension of 2.0 (95% CI 1.2, 3.4) and for preeclampsia of 1.9 (95% CI 0.7, 4.8). Results were similar when the analysis was restricted to data from primigravidas. CONCLUSION: We conclude that waist circumference up to 16 weeks' gestation can predict pregnancy-induced hypertension and preeclampsia. Therefore, waist circumference could form the basis for health promotion involving raising awareness of the importance of or urging weight reduction for women planning pregnancies.

Adult↗

Injecting drug use is a risk factor for deep vein thrombosis in women in Glasgow.

Three hundred and twenty-two consecutive women aged 16-70 years who presented with objectively confirmed symptomatic venous thromboembolism (VTE) were studied to determine precipitating factors for thrombosis. One hundred and eighty-seven presented with deep vein thrombosis (DVT), 116 with either definite or possible pulmonary embolism (PE) and 19 with both DVT and PE. Injecting drug use (IDU) via femoral vein puncture was a common risk factor for DVT, associated with 21.4% of all cases of DVT and 52.4% of cases of DVT in women under 40 years. All women with drug-related thrombosis presented with DVT. None presented with symptomatic PE. A number of clinically diagnosed DVT associated with IDU were also documented, suggesting that IDU may be the most common risk factor for DVT in our region. DVT associated with IDU presents significant management challenges.

Adolescent↗

Lipids and lipoprotein subfractions in women with PCOS: relationship to metabolic and endocrine parameters.

OBJECTIVE: Women with polycystic ovary syndrome (PCOS) exhibit an abnormal lipoprotein profile, characterized by raised concentrations of plasma triglyceride, marginally elevated low density lipoprotein (LDL)-cholesterol, and reduced high density lipoprotein (HDL)-cholesterol. However, a normal LDL-cholesterol level may be misleading since LDL exists as subpopulations of particles differing in size and atherogenic potential. Smaller LDL particles are more atherogenic and high concentrations often occur in association with elevated circulating triglyceride concentrations (but frequently normal total LDL-cholesterol), increased hepatic lipase activity (HL) and insulin resistance. Information on LDL subclasses and HL activity in women with PCOS is sparse. The aim of this study was to determine the concentrations of small, dense LDL (LDL-III) in women with PCOS relative to body mass index (BMI)-matched controls. We also examined the association of lipoprotein subfraction concentrations with endogenous sex hormone concentrations, since existing literature suggested that androgens up-regulate and oestrogens down-regulate HL activity, a key determinant of LDL subfraction distribution. DESIGN: Cross sectional study. PATIENTS: Fifty-two women with oligomenorrhoea and polycystic ovaries determined by ultrasound and BMI matched women with normal menstrual rhythm (NMR) and normal ovarian appearances (n = 14) were recruited from gynaecology clinics. Anthropometric data and fasting blood samples were obtained for metabolic, hormonal and LDL subfraction estimation and a heparin provocation test was used to estimate HL activity. RESULTS: Subjects with PCOS demonstrated higher waist:hip ratio (WHR), testosterone, triglyceride, VLDL-cholesterol concentrations, and HL activity (P < 0.05), whereas SHBG concentrations were significantly lower than controls. PCOS women had higher concentrations (38.0 vs. 25.0 mg/l; P = 0.026) and proportions (12.8 vs. 8.2%; P = 0.006) of small, dense LDL (LDL III), relative to controls. Within the PCOS group, plasma triglyceride and HL activity were the strongest univariate predictors of LDL III mass. They remained as independent predictors in multivariate analysis, and together accounted for 37% of its variability (P = 0.0002). Independent predictors of plasma triglyceride and HL in turn, were measures of fat distribution (waist circumference or WHR) and fasting insulin concentration. Serum testosterone concentration was not associated either in univariate or multivariate analysis with any of the measured lipid, lipoprotein or subfraction parameters, nor with HL activity in the women with PCOS. CONCLUSION: We conclude that women with polycystic ovary syndrome have increased hepatic lipase activity and mass and percentage of small, dense low density lipoprotein relative to body mass index-matched controls with normal menstrual rhythm and normal ovaries. Further, these metabolic perturbances appear related more closely to adiposity/insulin metabolism than to circulating androgen levels.

Adult↗

Management of venous thromboembolism in pregnancy.

Pulmonary thromboembolism (PTE) is the major cause of maternal death in the UK, with recent trends showing an increase in the numbers of deaths. Underlying PTE is the problem of deep venous thrombosis (DVT). An appreciation of risk factors, particularly, thrombophilia, and signs or symptoms suggestive of thromboembolism, coupled with objective diagnosis and treatment should reduce mortality and morbidity. There are particular considerations with regard to the management of thrombosis in pregnancy, especially the use of anticoagulants. Low-molecular-weight heparins are now replacing unfractionated heparin for the treatment of DVT and PTE in pregnancy.

Anticoagulants↗

Vaginal application of the nitric oxide donor isosorbide mononitrate for preinduction cervical ripening: a randomized controlled trial to determine effects on maternal and fetal hemodynamics.

OBJECTIVE: Our aim was to assess the effects of vaginally administered isosorbide mononitrate (a nitric oxide donor) on maternal and fetal hemodynamics in pregnant women at term. STUDY DESIGN: We conducted a randomized controlled trial. Women were randomly selected to receive vaginally administered isosorbide mononitrate, 20 mg (n = 13) or 40 mg (n = 11), or to undergo a vaginal examination only (n = 12). Maternal pulse, blood pressure, and fetal heart rate were recorded at baseline and then every 30 minutes until 360 minutes. Umbilical artery resistance index and pulsatility index measurements were performed at 0, 180, and 330 minutes. RESULTS: Maternal pulse rate was greater after the administration of isosorbide mononitrate, 20 or 40 mg, compared with the pulse rate in the vaginal examination-only group (greatest difference in means, 21 beats/min; P <.01). Maternal systolic and diastolic blood pressures were greater in the 20-mg and 40-mg isosorbide mononitrate groups than in the vaginal examination-only group (greatest difference in mean systolic and diastolic blood pressure, 15 and 16 mm Hg, respectively; P <.02 and P <.001, respectively). Fetal heart rate was greater in the 40-mg isosorbide mononitrate group than in either the 20-mg isosorbide mononitrate group or the vaginal examination-only group (difference in mean, 15 beats/min; P <.05). No woman required treatment for maternal or fetal tachycardia or maternal hypotension. Neither dose of isosorbide mononitrate had a significant effect on umbilical artery resistance or pulsatility index. CONCLUSIONS: Vaginal administration of 20 or 40 mg isosorbide mononitrate to pregnant women at term has an effect on both maternal and fetal hemodynamics, but this effect is not clinically significant.

Adolescent↗