下肢大关节手术围手术期抗凝治疗

静脉血栓栓塞症(venous thromboembolism, VTE)包括深静脉血栓形成和肺血栓栓塞症, 是下肢大关节手术后发生率高且后果严重的并发症, 因此术后抗凝治疗预防VTE受到越来越多骨科医师的重视。随着国内外抗凝治疗指南的推广应用, 下肢大关节手术后VTE发生风险及死亡率明显降低, 对此类患者术后常规抗凝治疗已成为骨科医师共识; 然而, 目前对于具体抗凝方案及疗程选择, 是否需要联合用药, 以及对合并复杂基础疾病患者的围手术期抗凝等问题仍有争议。本文对下肢大关节手术围手术期常用抗凝药物、抗凝方案、抗凝风险和并发症以及复杂情况下的抗凝治疗进行阐述。     

静脉血栓栓塞症的抗凝疗程及其影响因素

抗凝疗法是静脉血栓栓塞症(VTE)治疗,尤其是VTE二级预防治疗的重要部分.目前推荐的VTE二级预防的疗程一般为3～12个月.影响抗凝疗程的因素主要有初次VTE发作时是否具有易栓症、血栓诱发因素和临床特征,应根据每位患者的影响因素,权衡VTE复发的可能性和预防中出血的风险来决定疗程.疗程结束后还应重新评估影响因素和停止抗凝后VTE复发的风险决定是否延长抗凝时间.     

静脉血栓栓塞性疾病的合理抗凝治疗

静脉血栓栓塞性疾病(venous Thromboembolism,VTE)是指血液在深静脉腔内异常凝结,阻塞静脉管腔,引起相应的临床综合征,包括深静脉血栓形成和肺血栓栓塞症。倘若VTE患者未接受有效的抗凝治疗,常会导致较高的致死率和致残率,因此VTE又被喻为临床上的"潜伏炸弹",成为继心肌梗死、脑卒中后第三大致死性疾病。目前临床上存在多种抗凝药物及抗凝方案,关于VTE患者抗凝治疗的临床研究有很多,但对于血栓患者抗凝治疗的用药种类、用药时间、风险评估与监测等,并未形成一个良好的共识,静脉血栓形成患者常出现抗凝不足或抗凝过度的现象,尤其对于高龄、合并肝肾功能异常、肿瘤等特殊人群,临床上并未做到个体化抗凝治疗。本述评结合临床抗凝治疗常用药物,论述治疗指征及合适的治疗时限,并对血栓抗凝治疗的发展方向做出了展望,希望对业内同仁有所启发。     

新型抗凝药物及其治疗静脉血栓栓塞症的临床应用

在我国,新型抗凝药物正逐渐应用于静脉血栓栓塞症(VTE)的治疗中,主要包括Ⅹa因子抑制剂和Ⅱa因子抑制剂两大类。本文主要对各种新型抗凝药物治疗VTE的临床研究结果、使用方法及使用注意事项等方面进行阐述,以利于临床更好地使用这些药物,从而达到最佳治疗效果。     

围手术期静脉血栓栓塞症形成风险评估及抗凝药物管理

<正>肺血栓栓塞症和深静脉血栓形成(deep venous thrombosis,DVT)合称为静脉血栓栓塞症(venous thromboembolism, VTE),是同一个疾病在不同阶段、不同部位的2种重要临床表现形式。医院内VTE的发生风险与患者的住院病情、手术等治疗措施及并存的其他危险因素(如高龄、肥胖、卧床合并症等)有关。围手术期(从确定手术治疗时起,直到与     

抗凝治疗在危重型新型冠状病毒肺炎合并静脉血栓栓塞症中的应用

目的 探讨抗凝治疗在危重型新型冠状病毒肺炎(新冠肺炎)合并静脉血栓栓塞症(VTE)患者中的应用效果.方法 收集2020年1月30日至3月7日内蒙古科技大学包头医学院第一附属医院收治的3例危重型新冠肺炎患者的临床资料,记录患者的症状及辅助检查情况、治疗方法及预后,分析抗凝治疗对患者VTE的影响.结果 3例患者中,2例行无...     

静脉血栓栓塞症患者出院后抗凝治疗依从性现状及其影响因素

目的 探讨静脉血栓栓塞症(venous thromboembolism,VTE)患者出院后抗凝治疗依从性现状及其影响因素.方法 2020年9月至2021年2月,采用便利抽样法选取上海某三级甲等医院血管外科确诊为VTE的出院患者190例作为研究对象,使用一般情况调查表、Morisky用药依从性量表8条目(Morisky ...     

肺癌合并静脉血栓栓塞症患者的临床特点及预后分析

目的分析肺癌合并静脉血栓栓塞症(VTE)患者的临床特点及其预后。方法选取2013年2月至2015年2月肺癌合并VTE患者62例,其中肺血栓栓塞(PTE)36例,深静脉血栓(DVT)26例。均采用溶栓+抗凝或单纯抗凝进行治疗,观察分析肺癌合并VTE患者的临床特点及预后。结果 44例接受化疗后采用溶栓+抗凝的VTE患者中,30例有效,9例无效自动出院,5例死亡,有效率为68.18%。18例单纯抗凝治疗者中,11例有效,5例无效自动出院,2例死亡,有效率为61.11%。所有患者住院期间有效41例,有效率为66.13%;死亡7例,病死率为11.29%。结论 VTE是肺癌的主要并发症之一,其主要临床特点表现为胸闷气短、胸痛、咯血、呼吸急促、咳嗽以及胸腔积液等症状,及时确诊加上有效的治疗措施可缓解患者的病情,改善临床症状。     

低分子肝素及其临床应用研究的近况

肝素发现于1916年,作为抗凝剂使用只50多年。肝素治疗的并发症有出血、过敏反应、骨质疏松、肝素相关性血小板减小症及血栓栓塞。1976年Johoson等首先发现志愿者皮下注射低分子肝素(LMWH)时,在血浆中产生的抗活化因子X(抗-X_a),其活性比高分子肝素(HMWH)的抗-X_a活性高。同年,Andersson等报告体外实验用部分凝血活酶生成时间(APTT)和凝血酶时间(TT)测定肝素的抗凝活性,发现LMWH抗凝活性较低,但用抗-X_a测定其抗凝活却性相当高。1978年Lane等也证实了上述发现。本文复习文献对LMWH的抗凝特性、药物动力学和临床应用的研究近况作一综合介绍。     

恶性肿瘤合并静脉血栓栓塞107例临床分析

目的 探讨恶性肿瘤合并静脉血栓栓塞(VTE)患者的临床特征,为恶性肿瘤合并VTE的早期预防及诊治提供临床依据.方法 对我院2009年6月至2011年6月收治的107例恶性肿瘤合并静脉血栓患者的临床资料进行回顾性研究.结果 107例恶性肿瘤合并VTE患者中,单纯深静脉血栓(DVT) 90例(84.1％);肺血栓栓塞症(PTE)17例(15.9％),其中合并DVT 7例(6.5％,7/107).平均年龄(59.6±10.5)岁,≥60岁63例(58.9％).Ⅲ～Ⅳ期恶性肿瘤61例(57.0％).69例(64.5％)VTE发生于恶性肿瘤诊断后3个月内,43例(40.2％)VTE发生于手术后1个月内,其中术后1～7天30例(28.0％).91例DVT患者中84例接受抗凝治疗,49例治疗后好转,有效率为58.3％(49/84).PTE患者溶栓联合抗凝治疗2例,1例治疗后明显好转,1例好转;单纯抗凝治疗12例,3例明显好转,6例好转,3例无效.本组PTE患者抗凝溶栓治疗的有效率78.6％(11/14),病死率29.4％ (5/17).结论 恶性肿瘤诊断后3个月内、手术后1个月尤其是1周内,Ⅲ～Ⅳ期、≥60岁的患者高发VTE.VTE(尤其是PTE)可以增加恶性肿瘤患者的病死率,影响其预后.对于恶性肿瘤合并VTE患者的早期诊断与治疗是降低病死率及改善预后的关键.     

Anticoagulant therapy for venous thromboembolism during pregnancy: a systematic review and a meta‐analysis of the literature

Summary. Venous thromboembolism (VTE) is one of the most relevant causes of maternal death in industrialized countries. Low molecular weight heparin (LMWH), continued throughout the entire pregnancy and puerperium, is currently the preferred treatment for patients with acute VTE occurring during pregnancy. However, information on the efficacy and safety of anticoagulant drugs in this setting is extremely limited. We carried out a systematic review and a meta‐analysis of the literature to provide an estimate of the risk of bleeding complications and VTE recurrence in patients with acute VTE during pregnancy treated with antithrombotic therapy. The weight mean incidence (WMI) of bleeding and thromboembolic events and the corresponding 95% confidence interval (CI) were calculated. Eighteen studies, giving a total of 981 pregnant patients with acute VTE, were included. LMWH was prescribed to 822 patients; the remainder were treated with unfractionated heparin. Anticoagulant therapy was associated with WMIs of major bleeding of 1.41% (95% CI 0.60–2.41%; I) antenatally and 1.90% (95% CI 0.80–3.60%) during the first 24 h after delivery. The estimated WMI of recurrent VTE during pregnancy was 1.97% (95% CI 0.88–3.49%; I² 39.5%). Anticoagulant therapy appears to be safe and effective for the treatment of pregnancy‐related VTE, but the optimal dosing regimens remain uncertain.     

The prevention and treatment of venous thromboembolism in pregnancy

Introduction: Venous thromboembolism (VTE) in pregnancy represents an important cause of maternal morbidity and mortality in developed countries, with an incidence of 0.5–2.2 per 1000 pregnancies. In addition to hemostatic changes occurring during normal pregnancy, several risk factors have been identified. Thus, a variety of clinical conditions as well as fetal and maternal risks linked to a possible anticoagulant therapy should be considered for the management of VTE during pregnancy. Unfortunately, there is a paucity of high-quality evidence from randomized trials in this field, and current recommendations are based on observational studies or evidence gathered from studies in the non-pregnant population.

Areas covered: The purpose of this review is to summarize available evidence on the prevention and treatment of pregnancy-related VTE.

Expert commentary: Although the optimal prophylactic and therapeutic dosage has not yet been established, low-molecular-weight heparin (LMWH) represents the most efficacious and safe anticoagulant during pregnancy. Thus, after an accurate risk stratification of women during pregnancy and puerperium, LMWH should be recommended to women at risk for VTE and to those ones suffering from an acute event.     

Thrombophilia and pregnancy complications

Venous thromboembolism is the leading cause of pregnancy-associated morbidity and mortality. Women with thrombophilia have an increased risk of VTE in pregnancy and puerperium. In individuals with hereditary thrombosis risk factors a relative risk of pregnancy associated VTE ranging from 3.4 to 15.2 has been found. Women with previous VTE have an approximately 3.5-fold increased risk of recurrent VTE during pregnancy compared to non-pregnant periods. Data on the association of thrombophilia and pregnancy loss and pre-eclampsia are conflicting. Besides an established association with antiphospholipid antibodies, available data suggest associations for antithrombin deficiency, hyper-homo-cysteinemia, factor V Leiden, prothrombin G20210A variation and protein S-deficiency. A contribution of thrombophilia to the risk of pre-eclampsia is less well established. A limited number of prospective studies did not reveal an increased risk of pregnancy complications in unselected women with thrombosis risk factors. Data of only one controlled trial on the prevention of pregnancy loss with low molecular weight heparin (LMWH) are available, which revealed a strikingly positive effect. Thrombophilia screening might be justified in women with pregnancy loss and treatment with LMWH might be considered in those with pregnancy loss and thrombophilia. Further prospective studies and controlled interventional trials are urgently needed.     

孕产妇静脉血栓栓塞症相关风险因素分析

目的：探讨孕产妇发生静脉血栓栓塞症（venous thromboembolism，VTE）的相关危险因素。方法：采用回顾性病例对照研究，选取我院2010-2020年收治的38例发生VTE的孕产妇作为观察组，同时随机选取同时段我院199例未发生VTE的孕产妇作为对照组。将两组患者的高危因素、Caprini评分及《产科静脉血栓栓塞症综合防治上海共识》中孕产妇静脉血栓栓塞风险因素评分（简称孕产妇VTE评分）、实验室指标等因素纳入统计学分析。结果：产褥期发生VTE的比例最高(65.79%,25/38)。发生类型最高的为下肢深静脉血栓形成，其次为颅内静脉血栓形成。其中2例死亡原因为广泛颅内静脉血栓形成伴脑梗死出血转化，1例为晚期乳腺癌并发肺栓塞形成。logistic回归单因素分析显示剖宫产、孕产妇VTE风险评分、血红蛋白、血小板计数、D-二聚体、凝血酶原时间、活化部分凝血酶原时间有统计学差异（P＜0.05）。多因素回归分析结果显示孕产妇VTE风险评分、D-二聚体、凝血酶原时间、活化部分凝血酶原时间为孕产妇发生VTE的独立危险因素（P＜0.05）。结论:上海共识孕产妇VTE风险评分、D-二聚体、凝血酶原时间、活化部分凝血酶原时间为孕产妇发生VTE的独立危险因素。VTE的发生重在预防，专科VTE评分对孕产妇预防静脉血栓形成有临床意义。一旦发生VTE，结合实验室指标及必要的影像学指标早期诊断和治疗。     

Management of venous thromboembolism during pregnancy

Summary.  The incidence of venous thromboembolism (VTE) probably increases 2–4-fold in pregnancy and is higher after a caesarean section than after vaginal delivery. Management of VTE in pregnancy is challenging. Many diagnostic tests are less accurate in pregnant than in non-pregnant patients and some radiologic procedures expose the fetus to ionizing radiation, although this can be reduced by taking appropriate precautions. Compression ultrasonography (CUS) is the test of choice for deep vein thrombosis (DVT), whereas for PE, V/Q lung scan is the first-line test, followed by CUS if the results are non-diagnostic.
Anticoagulants that have been evaluated for the prevention and treatment of VTE in pregnancy include heparin and heparin compounds, and coumarin derivatives. When determining the optimal treatment regimens, it is important to consider: (i) the safety of the drug for the fetus and mother; (ii) the efficacy of the regimen; and (iii) the dose regimens for acute and secondary treatment, and during delivery and postpartum. Heparins are safer than coumarins for the fetus, as they do not cross the placental barrier. Heparins, particularly unfractionated heparin (UFH) and low molecular weight heparin (LMWH) tend also to be safer for the mother than other compounds. Of the two, LMWHs, although more expensive, are associated with lower rates of bleeding complications, and heparin-induced thrombocytopenia and osteoporosis, than UFH, and should therefore be the treatment of choice in VTE during pregnancy.
Patients with prior VTE or a hypercoagulable state have an increased risk of VTE during pregnancy. Depending on the presence of one or both of these factors, clinical surveillance, with anticoagulant treatment where necessary, is recommended.     

Pregnancy-associated thrombosis

Venous thromboembolism (VTE) occurs infrequently but is a leading cause of illness and death during pregnancy and the puerperium. In the general population the incidence of pregnancy associated VTE is approximately 1 in 1500 deliveries The risk of VTE is five times higher in a pregnant than in a non-pregnant woman. Postpartum the VTE-risk is even higher. Women with congenital abnormalities or persistent presence of antiphospholipid antibodies have an increased risk of VTE during pregnancy and the puerperium. In individuals with well defined hereditary thrombosis risk factors, such as the factor V:R506Q mutation, the factor II:G20210A variation, antithrombin-deficiency or protein C-deficiency, a relative risk of pregnancy associated VTE between 3.4 and 15.2 has been found. Women with previous VTE have an approximately 3.5 fold increased risk of recurrent VTE during pregnancy compared to non-pregnant periods. Our ability to diagnose pregnancy-associated VTE clinically is generally poor, since dyspnea, tachypnea, swelling and discomfort in the legs are common. Objective diagnosis is essential for treatment decisions. Exposure to radiation of less than 50,000 microGy (5 rad) has not been associated with a significant risk of fetal injury Therefore, besides sonography, routine diagnostic procedures should be performed, if clinically necessary. Heparin does not cross the placenta and is therefore the anticoagulant of choice. In case of acute thrombosis during pregnancy, treatment is performed like in nonpregnant patients. There is ongoing debate, whether or not pregnant women with previous venous thrombosis should routinely receive prophylactic anticoagulation. In patients who have hereditary antithrombin deficiency, antiphospholipid antibodies, a combined abnormality or a history of a severe thrombotic event (pulmonary embolism, extended deep vein thrombosis) should be advised to use prophylactic heparin during pregnancy, starting during the first trimester. Post partum prophylaxis should be given in all women with an increased risk for VTE.     

Prophylaxis with low‐dose low‐molecular‐weight heparin during pregnancy and postpartum: is it effective?

Summary. Background: The optimal approach for venous thrombosis (VTE) prophylaxis during pregnancy and postpartum in women with an increased risk of VTE is not established. Objectives: To evaluate the effectiveness, represented as the incidence of pregnancy‐related VTE, and safety, represented as incidence of postpartum hemorrhage (PPH), of a protocol recommending prophylaxis with low‐dose low‐molecular‐weight heparin (LMWH) in women at intermediate to high risk of VTE. Patients/methods: In this retrospective cohort study, we analyzed 34 women (44 pregnancies) with intermediate risk of VTE who received low‐dose LMWH for 6 weeks postpartum and 57 women (82 pregnancies) with high risk of VTE who received low‐dose LMWH during pregnancy and for 6 weeks postpartum. Pregnancy‐related VTE was defined as VTE during pregnancy or ≤ 3 months postpartum. PPH was defined as blood loss > 500 mL and severe PPH as blood loss > 1000 mL. Results: The incidence of pregnancy‐related VTE was 5.5% (95% CI, 2.4–12.3) despite prophylaxis with low‐dose LMWH. All events occurred in women at high risk, with a postpartum incidence of 7.0% (95% CI, 2.9–16.7) and antepartum incidence of 1.8% (95% CI, 0.4–9.2). The risk of PPH was 21.6% (95% CI, 14.3–31.3) and severe PPH 9.1% (95% CI, 4.7–16.9), which was not different in women who started LMWH postpartum and those who used LMWH during pregnancy. Conclusions: Although prophylaxis with low‐dose LMWH during pregnancy and postpartum proved to be safe, the risk of pregnancy‐related VTE is considerable in women with a high risk of VTE. VTE prophylaxis with low‐dose LMWH may not be sufficiently effective in these women.     

The risk of first venous thromboembolism during pregnancy and puerperium in double heterozygotes for factor V Leiden and prothrombin G20210A

Background : The risk of venous thromboembolism (VTE) during pregnancy in double heterozygous carriers of factor (F) V Leiden and prothrombin G20210A is not established. Hence, whether or not these women deserve antithrombotic prophylaxis when pregnant is unknown. Patients and methods : In the frame of a multicenter family study, 52 double heterozygous carriers of FV Leiden and prothrombin G20210A who had remained pregnant at least once before knowledge of thrombophilia, were retrospectively investigated with respect to the occurrence of first VTE during pregnancy and puerperium. They were compared with 104 heterozygous carriers of FV Leiden, 104 of prothrombin G20210A and 104 women without thrombophilia. Results : Double heterozygotes were similar to single heterozygous carriers and non-carriers for the age at first pregnancy, age at testing and rate of full-term pregnancies. No VTE during pregnancy was observed in the four groups of women, whereas in the puerperium it occurred in two double carriers (1.8% of pregnancies, 95% CI: 0.5–6.3), three single FV Leiden carriers (1.5%, 0.5–4.3), two single prothrombin G20210A carriers (1%, 0.2–3.6) and one non-carrier (0.4%, 0–2.5). Conclusions : The risk of first VTE during pregnancy and puerperium in double heterozygous carriers of FV Leiden and prothrombin G20210A is low and similar to that of single carriers. As for single heterozygotes, antithrombotic prophylaxis in asymptomatic double heterozygous carriers appears to be justified only in puerperium.     

ABO blood groups and risk of venous thromboembolism during pregnancy and the puerperium. A population-based, nested case-control study.

OBJECTIVES: To examine possible associations of ABO blood types with the risk of venous thromboembolism (VTE) in pregnancy and the puerperium. PATIENTS AND METHODS: We conducted a nested case-control study within a cohort of 71,729 women who gave birth to 126,783 children in the North Jutland County, Denmark, from 1980 to 2001. We identified 129 cases with VTE in pregnancy (n = 61) or the puerperium (n = 68), and 258 controls with no VTE. We collected information on ABO blood groups and possible maternal confounding factors and estimated the relative risk [odds ratio (OR)]. RESULTS: Women with an A or AB blood group had elevated risk estimates of VTE in pregnancy or the puerperium compared with women with a O blood group [adjusted ORs 2.4, 95% confidence interval (CI) 1.3, 4.3, and 2.0, 95% CI 0.7, 5.8, respectively]. No increased risk estimate was found for group B (adjusted OR 1.2, 95% CI 0.5, 3.0). The increased risk estimates of VTE for blood groups A and AB appeared present in both pregnancy (adjusted ORs of 3.9, 95% CI 1.5, 9.7, and 2.2, 95% CI 0.4, 12.5) and in the puerperium (adjusted ORs of 2.4, 95% CI 1.0, 4.9 and 2.7, 95% CI 0.8, 9.3). Furthermore, blood groups A and AB appeared to be associated with increased risk estimates for both DVT and pulmonary embolism. CONCLUSION: Keeping the modest statistical precision of our study in mind, blood groups A and AB may be associated with increased risk estimates for VTE in pregnancy and the puerperium.     

Correlation between thrombus regression and recurrent venous thromboembolism. Examining venographic and clinical effects of low-molecular-weight heparins: a meta-analysis.

We analyzed the correlation between thrombus regression on control venography performed after discontinuation of heparin therapy and recurrent venous thromboembolism (VTE) detected during clinical follow-up in randomized trials comparing low-molecular-weight heparin (LMWH) and unfractionated heparin (UFH) in patients with deep vein thrombosis (DVT). Data were abstracted from MEDLINE, conference abstracts and reference lists of previous reviews. Randomized, controlled trials comparing LMWH and UFH for the treatment of DVT using a combined venographic and clinical assessment and with at least 2 months of follow-up were selected. The proportions of patients with thrombus regression on control venography performed soon after discontinuation of heparin therapy and recurrent VTE at 2-6 months were independently collected by two researchers. Thirteen studies met the inclusion criteria. There was a strong inverse correlation between thrombus regression and recurrent VTE (r =- 0.70; P =0.008). The venographic effect varied between the different LMWHs (P = 0.013). A very strong correlation was found when the results were pooled by the type of LMWH used (r = - 0.84; P=0.037). No influence of the dose interval used on the venographic effect (P=0.156) or on recurrent VTE (P=0.218) was shown. The lack of thrombus regression in venography, performed soon after heparin discontinuation, was correlated with clinical recurrence. Non-invasive imaging techniques should be relevant to identify non-responders and to assess the optimal duration of initial heparin treatment in daily clinical practice.