Olivia Wu

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.

ABO(H) blood groups and vascular disease: a systematic review and meta-analysis

Summary.  Background: Associations between vascular disease and ABO(H) blood groups have a long history, but no consensus exists regarding its magnitude and significance, or whether it relates to all disorders equally. An accurate calculation of risk would allow direct assessment of whether the effects of non‐O status on thrombosis risk are of the magnitude predicted by its effect on von Willebrand factor/FVIII levels.

Oral contraceptives, hormone replacement therapy, thrombophilias and risk of venous thromboembolism: a systematic review The Thrombosis: Risk and Economic Assessment of Thrombophilia Screening (TREATS) Study

Combined oral contraceptives, oral hormone replacement therapy and thrombophilias are recognised risk factors for venous thromboembolism in women. The objective of this study was to assess the risk of thromboembolism among women with thrombophilia who are taking oral contraceptives or hormone replacement therapy, conducting a systematic review and metaanalysis. Of 201 studies identified, only nine met the inclusion criteria. Seven studies included pre-menopausal women on oral contraceptives and two studies included peri-menopausal women on hormone replacement therapy. For oral contraceptive use, significant associations of the risk of venous thromboembolism were found in women with factor V Leiden (OR 15.62; 95%CI 8.66 to 28.15); deficiencies of antithrombin (OR 12.60; 95%CI 1.37 to 115.79), protein C (OR 6.33; 95%CI 1.68 to 23.87), or protein S (OR 4.88; 95%CI 1.39 to 17.10), elevated levels of factor VIIIc (OR 8.80; 95%CI 4.13 to 18.75); and factor V Leiden and prothrombin G20210A (OR 7.85; 95%CI 1.65 to 37.41). For hormone replacement therapy, a significant association was found in women with factor V Leiden (OR 13.16; 95%CI 4.28 to 40.47). Although limited by the small number of studies, the findings of this study support the presence of interaction between thrombophilia and venous thromboembolism among women taking oral contraceptives. However, further studies are required to establish with greater confidence the associations of these, and other, thrombophilias with venous thromboembolism among hormone users.

Elevated Troponin after Stroke: A Systematic Review

Background: Troponin levels are elevated in some acute stroke patients, but the clinical significance of this is unclear. Methods: We conducted a systematic review of studies measuring troponin within 7 days of symptom onset in acute stroke patients. Results: We identified 15 studies (2,901 patients). Overall 18.1% (95% CI 13.6–22.6) had a positive troponin level. These patients were more likely to have electrocardiogram (ECG) changes suggestive of myocardial ischemia (OR 3.0; 95% CI 1.5–6.2), and there was an independent association with death (OR 2.9; 95% CI 1.7–4.8). Conclusion: Elevated troponin level after acute stroke is common and is associated with ECG changes suggestive of myocardial ischemia and increased risk of death.

Randomised comparison of uterine artery embolisation (UAE) with surgical treatment in patients with symptomatic uterine fibroids (REST trial): 5-year results.

Please cite this paper as: Moss J, Cooper K, Khaund A, Murray L, Murray G, Wu O, Craig L, Lumsden M. Randomised comparison of uterine artery embolisation (UAE) with surgical treatment in patients with symptomatic uterine fibroids (REST trial): 5‐year results. BJOG 2011;118:936–944.

Impact of Prevalent Fractures on Quality of Life: Baseline Results From the Global Longitudinal Study of Osteoporosis in Women

OBJECTIVE To examine several dimensions of health-related quality of life (HRQL) in postmenopausal women who report previous fractures, and to provide perspective by comparing these findings with those in other chronic conditions (diabetes, arthritis, lung disease). PATIENTS AND METHODS Fractures are a major cause of morbidity among older women. Few studies have examined HRQL in women who have had prior fractures and the effect of prior fracture location on HRQL. In this observational study of 57,141 postmenopausal women aged 55 years and older (enrollment from December 2007 to March 2009) from 17 study sites in 10 countries, HRQL was measured using the European Quality of Life 5 Dimensions Index (EQ-5D) and the health status, physical function, and vitality questions of the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36). RESULTS Reductions in EQ-5D health-utility scores and SF-36-measured health status, physical function, and vitality were seen in association with 9 of 10 fracture locations. Spine, hip, and upper leg fractures resulted in the greatest reductions in quality of life (EQ-5D scores, 0.62, 0.64, and 0.61, respectively, vs 0.79 without prior fracture). Women with fractures at any of these 3 locations, as well as women with a history of multiple fractures (EQ-5D scores, 0.74 for 1 prior fracture, 0.68 for 2, and 0.58 for >/=3), had reductions in HRQL that were similar to or worse than those in women with other chronic diseases (0.67 for diabetes, 0.69 for arthritis, and 0.71 for lung disease). CONCLUSION Previous fractures at a variety of bone locations, particularly spine, hip, and upper leg, or involving more than 1 location are associated with significant reductions in quality of life.

Screening for thrombophilia in high-risk situations: a meta-analysis and cost-effectiveness analysis

Laboratory testing for the identification of heritable thrombophilia in high‐risk patient groups have become common practice; however, indiscriminate testing of all patients is unjustified. The objective of this study was to evaluate the cost‐effectiveness of universal and selective history‐based thrombophilia screening relative to no screening, from the perspective of the UK National Health Service, in women prior to prescribing combined oral contraceptives and hormone replacement therapy, women during pregnancy and patients prior to major orthopaedic surgery. A decision analysis model was developed, and data from meta‐analysis, the literature and two Delphi studies were incorporated in the model. Incremental cost‐effectiveness ratios (ICERs) for screening compared with no screening was calculated for each patient group. Of all the patient groups evaluated, universal screening of women prior to prescribing hormone replacement therapy was the most cost‐effective (ICER £6824). In contrast, universal screening of women prior to prescribing combined oral contraceptives was the least cost‐effective strategy (ICER £202 402). Selective thrombophilia screening based on previous personal and/or family history of venous thromboembolism was more cost‐effective than universal screening in all the patient groups evaluated.

The predictive accuracy of anti-Müllerian hormone for live birth after assisted conception: a systematic review and meta-analysis of the literature

BACKGROUND Anti-Müllerian hormone (AMH) is an established marker of ovarian reserve and a good predictor of poor or excessive ovarian response after controlled hyperstimulation. However, it is unclear whether it can predict the ultimate outcome of assisted conception, live birth. We undertook a systematic review and meta-analysis to examine whether AMH is a predictor of live birth in women undergoing assisted conception. METHODS The study was conducted according to the PRISMA guidelines. PubMed, Embase, Medline, Web of Knowledge and the Cochrane trial register and unpublished literature were searched. Studies fulfilling the eligibility criteria were included in the systematic review and those with extractable data were included in the meta-analysis. Quality assessment was performed with the QUADAS 2 checklist. A summary estimate of diagnostic odds ratio (DOR) was derived using the random effects model for binary data. A hierarchical summary receiver operating characteristic model provided pooled estimates before and after adjusting for age and AMH assay as covariates. RESULTS Out of 361 non-duplicate studies, 47 were selected; 17 met the eligibility criteria and 13 had extractable data and thus were included in the meta-analysis. Three out of the 13 studies included only women with expected low ovarian reserve and were analysed individually from the remaining 10 to minimize heterogeneity. The DOR for women with unknown ovarian reserve (n = 5764 women) was 2.39 (95% confidence interval (CI): 1.85-3.08). After adjustment for age the DOR was little changed at 2.48 (95% CI: 1.81-3.22) and the DOR adjusted for AMH assay was almost identical at 2.42 (95% CI: 1.86-3.14). For women with expected low ovarian reserve (n = 542 women) the DOR was 4.63 (95% CI: 2.75-7.81). CONCLUSIONS AMH, independently of age, has some association with predicting live birth after assisted conception and may be helpful when counselling couples before undergoing fertility treatment. However, its predictive accuracy is poor.

Risk of acute myocardial infarction with nonselective non-steroidal anti-inflammatory drugs: a meta-analysis

The use of cyclo-oxygenase 2 selective nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with increased risk of acute myocardial infarction (AMI). The association between the risks of AMI with nonselective NSAIDs is less clear. We reviewed the published evidence and assessed the risk of AMI with nonselective NSAIDs. We performed a meta-analysis of all studies containing data from population databases that compared the risk of AMI in NSAID users with that in non-users or remote NSAID users. The primary outcome was objectively confirmed AMI. Fourteen studies met predefined criteria for inclusion in the meta-analysis. Nonselective NSAIDs as a class was associated with increased AMI risk (relative AMI risk 1.19, 95% confidence interval [CI] 1.08 to 1.31). Similar findings were found with diclofenac (relative AMI risk 1.38, 95% CI 1.22–1.57) and ibuprofen (relative AMI risk 1.11, 95% CI 1.06 to 1.17). However, this effect was not observed with naproxen (relative AMI risk 0.99, 95% CI 0.88–1.11). In conclusion, based on current evidence, there is a general direction of effect, which suggests that at least some nonselective NSAIDs increase AMI risk. Analysis based on the limited data available for individual NSAIDs, including diclofenac and ibuprofen, supported this finding; however, this was not the case for naproxen. Nonselective NSAIDs are frequently prescribed, and so further investigation into the risk of AMI is warranted because the potential for harm can be substantial.

The GOAL study : a prospective examination of the impact of factor V Leiden and ABO(H) blood groups on haemorrhagic and thrombotic pregnancy outcomes

Factor V Leiden (FVL) and ABO(H) blood groups are the common influences on haemostasis and retrospective studies have linked FVL with pregnancy complications. However, only one sizeable prospective examination has taken place. As a result, neither the impact of FVL in unselected subjects, any interaction with ABO(H) in pregnancy, nor the utility of screening for FVL is defined. A prospective study of 4250 unselected pregnancies was carried out. A venous thromboembolism (VTE) rate of 1·23/1000 was observed, but no significant association between FVL and pre‐eclampsia, intra‐uterine growth restriction or pregnancy loss was seen. No influence of FVL and/or ABO(H) on ante‐natal bleeding or intra‐partum or postpartum haemorrhage was observed. However, FVL was associated with birth‐weights >90th centile [odds ratio (OR) 1·81; 95% confidence interval (CI95) 1·04–3·31] and neonatal death (OR 14·79; CI95 2·71–80·74). No association with ABO(H) alone, or any interaction between ABO(H) and FVL was observed. We neither confirmed the protective effect of FVL on pregnancy‐related blood loss reported in previous smaller studies, nor did we find the increased risk of some vascular complications reported in retrospective studies.