Prevention of venous thromboembolism in pregnancy

Venous thromboembolic complications (VTE) are a leading causes of maternal mortality in the developed World. To reduce the incidence VTE in pregnancy, and improve outcomes, a wider understanding of the risk factors involved and a better identification of women at risk of thrombosis coupled with effective thromboprophylaxis are required. The common risk factors for VTE in pregnancy are: age over 35 years; obesity; operative delivery (especially emergency Caesarean Section in labour); thrombophilia; and a family or personal history of thrombosis suggestive of an underlying thrombophilia. As warfarin is unsuitable for use in pregnancy because of problems with embryopathy and risk of fetal bleeding, optimal thromboprophylaxis in pregnancy centres on the use of low-molecular-weight heparin (LMWH). There is now extensive experience of the safety and efficacy of LMWH in pregnancy. LMWH's, such as enoxaparin and dalteparin, have clinical and practical advantages compared with unfractionated heparin in terms of improved safety (significantly lower incidence of osteoporosis and heparin induced thrombocytopenia), and patient convenience with once daily dosing for the majority of women. Thus LMWH is now the agent of choice in pharmacological thromboprophylaxis in pregnancy     

Risk-based evaluation of thromboprophylaxis among surgical inpatients: are low risk patients treated unnecessarily?

Background  Venous thromboembolism is a common source of morbidity and mortality but a variety of preventative measures are available. Aims  To audit the current practice of thromboprophylaxis and compare against published protocols. Methods  Three-hundred and seventy-six (376) surgical patients were surveyed prospectively. A Performa was completed recording the presence of up to 11 risk factors. A risk score was calculated and the use of specific thromboprophylatic measures identified. Results  Heparin thromboprophylaxis was widely used, eight patients (who were on aspirin therapy) failed to receive any prophylaxis (risk factors 4–6). In addition there were 60 patients at low risk (risk score <2) received LMWH from which they were unlikely to benefit. Conclusions  Thromboembolic prophylaxis is widely but unselectively applied. Adoption of a risk: benefit ratio approach should ensure those who would benefit from thromboprophylaxis are adequately treated while those in whom thromboprophylaxis is not indicated are spared unnecessary therapy.     

Prevention of deep vein thrombosis in orthopedic surgery

In the absence of thromboprophylaxis, venous thromboembolism (VTE) affects about 50 to 80% of the patients after total hip replacement (THR), total knee replacement (TKR), or hip fracture surgery. Since stratification of patients in those who will become symptomatic and those who will not, is not possible, primary high risk thromboprophylaxis should be provided to all patients undergoing major orthopedic surgery of the lower extremity. Various non-pharmacologic and pharmacologic thromboprophylactic measures have been evaluated. With regard to pharmacologic thromboprophylaxis unfractionated heparin has now almost completely been replaced by low molecular weight heparin (LMWH) for VTE prophylaxis. The use of acetylsalicylic acid for thromboprophylaxis in patients undergoing major orthopedic surgery of the lower extremities is not recommended. The optimal beginning of LMWH thromboprophylaxis is either 2 hours preoperatively or 6 to 8 hours postoperatively. Extended thromboprophylaxis (beyond 7 to 10 days after surgery) is recommended for high-risk patients. New antithrombotics, such as fondaparinux or (xi)melagatran, significantly reduce the risk of asymptomatic but not of symptomatic VTE compared to LMWH. In the light of other potential side effects (e.g., an increased bleeding risk) and high costs the role of these new drugs in the prophylaxis of VTE in patients undergoing major orthopedic surgery of the lower extremities remains to be established.     

Warfarin-induced skin necrosis

Skin necrosis is a rare but serious side-effect of treatment with warfarin. At particular risk are those with various thrombophilic abnormalities, especially when warfarinization is undertaken rapidly with large loading doses of warfarin. With the increasing number of patients anticoagulated as out-patients for thromboprophylaxis, we are concerned that the incidence of skin necrosis may increase. If skin necrosis does occur, prompt remedial action may be of benefit in preventing permanent tissue damage.     

Implementation of antithrombotic management in atrial fibrillation

The aim of the study was to assess the extent to which published recommendations on the antithrombotic management of atrial fibrillation had been adopted into clinical practice in a busy district general hospital, and the impact of clinical audit on subsequent management. In the initial audit, 185 consecutive patients with atrial fibrillation were studied using their case notes to identify any further clinical risk factors for stroke. A management algorithm stratified patients with atrial fibrillation into high, moderate, or low risk of stroke according to the individual stroke risk factors. For patients at high risk, the correct treatment is warfarin unless there are specific contraindications. For patients at moderate risk, the correct management is aspirin unless there are specific contraindications. Patients at low risk should receive no thromboprophylaxis. The clinical risks of stroke and thromboprophylaxis on discharge from hospital were recorded. An extensive education programme on stroke prevention in atrial fibrillation was undertaken. Six months later a further 185 consecutive patients with atrial fibrillation were audited. Overall, a large proportion (306/370; 83%) of patients were at high risk of stroke. In the initial audit, antithrombotic management was correct in 89 patients (48%). In the follow up audit, antithrombotic management was correct in 135 patients (73%) (p < 0. 00001). If this improvement in management were extrapolated to all hospital patients in the United Kingdom, approximately 1400 strokes/year could be avoided. Despite broad consensus in recent publications, antithrombotic management of atrial fibrillation remains imperfect, with many patients exposed to unnecessarily high risk of stroke.     

Prevention of venous thromboembolism in medically ill patients: a clinical update

The risk of venous thromboembolism (VTE) in hospitalised medically ill patients is often underestimated, despite the fact that it remains a major cause of preventable morbidity and mortality in this group. It is not well recognised that the risk of VTE in many hospitalised medically ill patients is at least as high as in populations after surgery. This may partly be attributed to the clinically silent nature of VTE in many patients, and the difficulty in predicting which patients might develop symptoms or fatal pulmonary embolism. Two large studies, Prospective Evaluation of Dalteparin Efficacy for Prevention of VTE in Immobilized Patients Trial and prophylaxis in MEDical patients with ENOXaparin, have shown that low-molecular-weight heparins provide effective thromboprophylaxis in medically ill patients, without increasing bleeding risk. Recent guidelines from the American College of Chest Physicians recommend that acutely medically ill patients admitted with congestive heart failure or severe respiratory disease, or those who are confined to bed and have at least one additional risk factor for VTE, should receive thromboprophylaxis.     

Risk stratification and utilisation of thrombo-embolism prophylaxis in a medical-surgical ICU: a hospital-based study

To assess the risk for venous thrombo-embolism (VTE) and the utilisation of VTE prophylaxis in an open medical-surgical intensive care unit (ICU), patients were admitted and enrolled to the ICU at a multispecialty, tertiary care teaching hospital in Mumbai, for an observational study during a 3-month period. Risk factors for VTE and methods of VTE prophylaxis used were noted. Risk stratification was done, and the consultants attending the ICUs filled a questionnaire about VTE awareness, preferences and usage of VTE prophylaxis methods and reasons for not using thromboprophylaxis. Of 580 admissions, 488 were included in the study. As per the risk stratification, thromboprophylaxis was indicated in 466 (95%). The study group had an average VTE risk of 5.74, with a mean risk of 6.48 in medical patients and 5.0 in surgical patients. The most common risk factors in medical patients were bed rest >72 hours (56%), age >60 years (49.6%) and age 40-60 years (38.4%). Among surgical patients, the most common risk factors were major surgery (80.25%), central venous access (59.24%) and age 40-60 years (46.6%). Overall, VTE prophylaxis was used in 229 patients (47%), with 127 (55%) medical and 102 (45%) surgical patients. The most common methods of VTE prophylaxis used were elastic stockings (24.2%), low molecular weight heparin (15%) and low molecular weight heparin and stockings both (9.6%). Fear of bleeding was the commonest reason cited for the underutilisation of VTE prophylaxis. Almost half of all high-risk patients admitted to the ICU didn't receive any thromboprophylaxis. Consistent practice patterns of ICUs, and continuing medical education programmes addressing VTE prophylaxis will help improve the usage of VTE prophylaxis.     

Effect of statins on risk of coronary disease: a meta-analysis of randomized controlled trials

CONTEXT: Lowering low-density lipoprotein cholesterol (LDL-C) is known to reduce risk of recurrent coronary heart disease in middle-aged men. However, this effect has been uncertain in elderly people and women. OBJECTIVE: To estimate the risk reduction of coronary heart disease and total mortality associated with statin drug treatment, particularly in elderly individuals and women. DATA SOURCES: Trials published in English-language journals were retrieved by searching MEDLINE (1966-December 1998), bibliographies, and authors' reference files. STUDY SELECTION: Studies in which participants were randomized to statin or control treatment for at least 4 years and clinical disease or death was the primary outcome were included in the meta-analysis (5 of 182 initially identified). DATA EXTRACTION: Information on sample size, study drug duration, type and dosage of statin drug, participant characteristics at baseline, reduction in lipids during intervention, and outcomes was abstracted independently by 2 authors (J.H. and S.V.) using a standardized protocol. Disagreements were resolved by consensus. DATA SYNTHESIS: Data from the 5 trials, with 30 817 participants, were included in this meta-analysis. The mean duration of treatment was 5.4 years. Stati n drug treatment was associated with a20% reduction in total cholesterol, 28% reduction in LDL-C, 13% reduction in triglycerides, and 5% increase in high-density lipoprotein cholesterol. Overall, statin drug treatment reduced risk 31 % in major coronary events (95% confidence interval [CI], 26%-36%) and 21 % in all-cause mortality (95% CI, 14%-28%). The risk reduction in major coronary events was similar between women (29%; 95% Cl, 13 %-42 %) and men (31 %; 95% CI, 26%-35%), and between persons aged at least 65 years (32%; 95% CI, 23%-39%) and persons younger than 65 years (31 %; 95% CI, 24%-36%). CONCLUSIONS: Our meta-analysis indicates that reduction in LDL-C associated with statin drug treatment decreases the risk of coronary heart disease and all-cause mortality. The risk reduction was similar for men and women and for elderly and middle-aged persons.     

Direct thrombin inhibitors: novel antithrombotics on the horizon in the thromboprophylactic management of atrial fibrillation

Antithrombotic agents have verified efficacy in reducing the thromboembolic risk associated with atrial fibrillation. This article focuses on the emergence of a new oral direct thrombin inhibitor, ximelagatran, into the arena of atrial fibrillation thromboprophylaxis. This review does not cover atrial fibrillation in the context of valvular heart disease. The efficacy of aspirin and warfarin will be discussed briefly.     

结直肠手术后静脉血栓的发生与预防

目前,腹部外科手术后静脉血栓(VTE)的发病率逐年升高,VTE可导致静脉栓塞,严重者可引起致死性的肺栓塞。与其他腹部外科手术相比,结直肠手术患者术后发生VTE的风险更高,很多临床医师经常忽视这类患者术后血栓的预防。研究表明,使用低分子肝素或未分级肝素对结直肠患者进行术后的血栓预防,均能有效预防结VTE形成。低分子肝素因其使用次数少,不良反应少的特点被广泛使用。     

Evaluation of neonatal sepsis screening in a tropical area. Part II: Evaluation of intrapartum chemoprophylaxis protocol

The authors report on an analysis of a chemoprophylaxis protocol at the University Hospital of Guadeloupe in the Caribbean. This study comprised 6,060 consecutive deliveries and was initiated to assess the application of an intrapartum chemoprophylaxis protocol, evaluate its results, and try to identify possible necessary modifications to the existing protocol. Although more than 90% of women had at least one bacterial screening (vaginal or urinary) during the last trimester of pregnancy, approximately 75% of mothers who were heavily colonized group B streptococcus (GBS) at delivery were not detected by this systematic screening. As is also reported in other tropical areas where a great proportion of neonatal sepsis occurs in term babies, low birthweight was not a specific risk factor in this study when controlling for other major risk factors such as fever and premature rupture of membranes. Intrapartum chemoprophylaxis was associated with an approximate threefold decrease in the risk of GBS neonatal bacteraemia among at risk deliveries. The results suggest that, in our tropical context, prolonged rupture of membranes of at least 12 hours' duration should be considered as a cause for intrapartum chemoprophylaxis as it accounted for the majority of cases of neonatal bacteraemia that escaped the existing protocol.     

Apixaban versus enoxaparin for thromboprophylaxis after total hip or knee arthroplasty：A meta-analysis of randomized controlled trials

Background  Enoxaparin is routinely used for prevention of venous thromboembolism (VTE) after total hip or knee arthroplasty. The purpose of this study was to compare the efficacy and safety of apixaban, a newly oral direct inhibitor of factor Xa versus enoxaparin.

Methods  We performed a meta-analysis of relevant randomized-controlled trials (RCTs) identified in PubMed, Cochrane Library, Embase China Biological Medical Literature database, Countries Journal full-text database, VIP database, and WanFang database. The primary efficacy outcome for our meta-analysis was all VTE and all-cause mortality. The secondary efficacy outcomes included major VTE, non-fatal pulmonary embolism, and mortality. The primary safety outcome was bleeding events, categorized as major, clinically relevant non-major, or minor events.

Results  Four RCTs, involving 14 065 patients, were included in our meta-analysis. Compared to enoxaparin, thromboprophylaxis with apixaban was associated with significantly fewer VTE and all-cause mortality (8346 patients, risk ratio (RR): 0.63, 95% CI 0.42–0.95) and similar incidence of bleeding events (major bleeding, 11 525 patients, RR 0.76, 95% CI 0.43–1.33; clinically relevant non-major bleeding, 11 525 patients, RR 0.83, 95% CI 0.69–1.01; and minor bleeding, 11 828 patients, RR 0.93, 95% CI 0.79–1.09). However, our meta-analysis revealed similar effects of apixaban with enoxaparin for thromboprophylaxis with regard to the secondary efficacy outcomes.

Conclusions  Apixaban was more effective than recommended dose of enoxaparin and had a similar safety profile for thromboprophylaxis after hip and knee arthroplasty. But more evidence, especially well designed head-to-head RCTs, is needed to confirm the superior efficacy of apixaban.

     

Estrogen treatment of postmenopausal women. Benefits and risks

Estrogen treatment of postmenopausal women is effective in relieving the symptoms of vasomotor instability and urogenital atrophy; estrogen treatment is effective in preventing accelerated bone loss and osteoporosis in young women following castration, but in postmenopausal women aging is a more important determinant of accelerated bone loss than is decreased estrogen secretion. Low-dose estrogen treatment of postmenopausal women neither prevents nor increases the risk of arteriosclerotic cardiovascular disease or cerebral vascular disease. It cannot be definitively established that estrogen treatment of postmenopausal women causes an increased incidence of breast tumors, but it is clear that such treatment does not prevent these tumors. It is established that estrogen treatment of postmenopausal women increases the risk ratio of endometrial carcinoma.     

Lipids in women: screening and treatment

Hyperlipidemia is a risk factor for coronary heart disease (CHD) in both men and women, although the association between total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and CHD risk differs in men and women. Although several clinical trials of lipid lowering for both primary and secondary prevention of CHD have been conducted, women have not always been included, have been included in small numbers, or have not had their results analyzed separately. CHD risk assessment is an important component of decision making about screening and treatment of hyperlipidemia. This article presents guidelines for screening and treatment of hyperlipidemia in women with CHD, in healthy women, and in women at risk for CHD.     

定量分析两种治疗方案与危险指数对慢性髓系白血病临床缓解率的影响

目的：定量分析两种治疗方案与危险指数对慢性髓系白血病（CML）临床缓解率的影响。方法：按治疗方案与Sokal危险指数分别进行分组,定量分析三尖杉酯碱联合阿糖胞苷（HA）与羟基脲（Hu)二种治疗方案和病人初诊时所处的危险度对慢性期CML患者所获临床疗效的影响。结果：尽管HA方案治疗初诊CML慢性期患者的近期疗效优于Hu,但它并不能延长病人的慢性期维持时间（DCP）,而且病人的危险指数对完全缓解率（CR）,获CR所需时间及DCP的影响均远超出治疗方案的作用。结论：HA方案不能延长病人的DCP,不宜作为初诊CML慢性期患者的一线治疗方案,按危险指数将病人作出合适分层,有利于治疗方案的合理选择及科学评价。。     

定量分析两种治疗方案与危险指数对慢性髓系白血病临床缓解率的影响

目的定量分析两种治疗方案与危险指数对慢性髓系白血病(CML)临床缓解率的影响。方法按治疗方案与Sokal危险指数分别进行分组,定量分析三尖杉酯碱联合阿糖胞苷(HA)与羟基脲(Hu)二种治疗方案和病人初诊时所处的危险度对慢性期CML患者所获临床疗效的影响。结果尽管HA方案治疗初诊CML慢性期患者的近期疗效优于Hu,但它并不能延长病人的慢性期维持时间(DCP);而且病人的危险指数对完全缓解率(CR)、获CR所需时间及DCP的影响均远超出治疗方案的作用。结论HA方案不能延长病人的DCP,不宜作为初诊CML慢性期患者的一线治疗方案;按危险指数将病人作出合适分层,有利于治疗方案的合理选择及科学评价。     

Effect of medical thromboprophylaxis on mortality from pulmonary embolus and major bleedingy

Background

Several studies have failed to discover a beneficial effect of medical thromboprophylaxis on mortality.

Aims

To examine the relative influence of acute fatal pulmonary embolism (PE) and fatal major haemorrhage on overall mortality in medical patients treated with low molecular weight heparin (LMWP) for prophylaxis.

Methods

The author compared deaths from the above factors using data from a recent Cochrane Collaboration meta-analysis. Data from trials satisfying the criteria of the Cochrane analysis plus additional exclusions to avoid bias were pooled to produce point estimates of mortality from PE and major bleeds to estimate net mortality benefit. Estimates were then subject to limited sensitivity analysis based on reported epidemiological data.

Results

Reported PE and major bleeds were 0.44 per cent and 0.27 per cent, respectively. The corresponding case-specific mortality rates were 30.8 per cent and 12.8 per cent and the relative risk reduction (RRR) for PE was 23.2 per cent. Estimated deaths from major bleeds exceeded PE deaths avoided by a small margin (3/100,000 patients given prophylaxis). This excess increased to 30/100,000 when more plausible literature values for PE case fatality rates were applied.

Conclusion

Medical thromboprophylaxis has a finely balanced effect on mortality but may increase it. Such an effect would explain the failure to discover a mortality benefit from medical thromboprophylaxis. Further work, including a formal meta-analysis and additional clinical studies, is required to confirm this picture.     

Lipid screening in women

Evidence of the benefits of lowering cholesterol in various populations continues to grow, but questions persist about screening and treatment of lipid disorders in women. In this paper, we review the distinct features of the epidemiology of lipids and coronary heart disease in women and data from recent long-term treatment trials specific to women. Although data from primary prevention trials in women remain sparse, recent trials demonstrating benefits of cholesterol reduction across a broad range of cholesterol levels and cardiac risk in men and women bolster the conclusion that benefits may extend to asymptomatic women who are otherwise at high risk for coronary disease. Periodic lipid screening beginning in middle age will identify most women who are at high enough risk to merit drug therapy or more intensive individual lifestyle interventions. More detailed consideration of age, diabetes, blood pressure, specific lipid levels, or the ratio of total cholesterol to high-density lipoprotein cholesterol, and other risk factors can more accurately estimate individual risk of coronary heart disease and identify high-risk women most likely to benefit from lipid reduction. Advice about healthy diet, weight control, and physical activity can benefit all women, but authorities differ on the benefits of routine lipid screening in low-risk younger women.     

Rational thromboprophylaxis in medical inpatients: not quite there yet

Routine thromboprophylaxis in hospitalised medical patients is based on trials that predominantly use asymptomatic deep vein thrombosis (DVT) as the endpoint. As asymptomatic DVT is 10-30-fold more common than symptomatic DVT, this exaggerates estimates of benefit and cost-effectiveness. Based on symptomatic disease, the number needed to treat per venous thromboembolism (VTE) prevented is high (150-1600), and the true cost-effectiveness of thromboprophylaxis for symptomatic event reduction is uncertain. The incidence of major bleeding among patients receiving prophylaxis is at least equal to the reduction in clinical VTE. Routine thromboprophylaxis in hospitalised medical patients is not warranted, and better patient selection is needed.     

子宫内膜癌、子宫内膜非典型增生保留生育功能后助孕策略

子宫内膜癌及子宫内膜非典型增生的发病率逐渐升高,呈年轻化趋势,且保留生育功能的需求增加。以高效孕激素为基础的子宫内膜癌和子宫内膜非典型增生保留生育功能治疗方法能达到高的完全缓解率,但是生育力依然低下。以“妊娠为目的”积极助孕策略受到学者重视,但是关于子宫内膜癌和子宫内膜非典型增生保留生育功能后助孕缺乏系统研究。本文就保留生育功能治疗后助孕时机、助孕方案以及助孕中的难点进行探究。