抗凝剂预防膝关节镜术后血栓发生的Meta分析

doi:10.3877/cma.j.issn.1674-134X.2023.03.007

目的

评价膝关节镜术后是否运用抗凝剂对下肢静脉血栓栓塞症(VTE)的预防效果。

方法

计算机检索PubMed、荷兰医学文摘(EMbase)、循证医学图书馆(Cochrane Library)、中国知网、万方等5个数据库，检索建库至2022年9月所有对比膝关节镜术后是否预防性使用抗凝药物的随机对照试验(RCTs)，排除对照组使用抗凝药物，或试验组使用非药物抗凝的相关试验，由两名研究者独立筛选文献，对纳入的文献进行质量评价和数据提取，并选取肺栓塞(PE)发生率、有症状DVT发生率、下肢无症状近端DVT发生率作为疗效观察指标，严重出血率、轻微出血率作为安全性观察指标。采用RevMan 5.4软件进行Meta分析。

结果

最终纳入8篇文献，均为RCT，共4 302例患者。膝关节镜术后预防性抗凝组与不抗凝组PE发生率差异无统计学意义[相对危险度(RR)＝1.36，95%置信区间(CI)(0.37，4.97)，P＝0.64]；预防性抗凝组术后症状性DVT发生率低于不抗凝组[RR＝0.32，95%CI(0.16，0.63)，P＝0.001]；预防性抗凝组下肢无症状近端DVT发生率低于不抗凝组[RR＝0.17，95%CI(0.06，0.48)，P＝0.0007]；两组间严重出血发生率差异无统计学意义[RR＝1.44，95%CI(0.25，8.14)，P＝0.68]；预防性抗凝组轻微出血发生率高于不抗凝组，差异具有统计学意义[RR＝1.47，95%CI(1.11，1.94)，P＝0.006]。

结论

膝关节镜术后预防性使用抗凝剂可有效降低症状性DVT和无症状近端DVT的发生率，且不会增加严重出血的风险。但无论是否抗凝，膝关节镜术后PE、症状性DVT、无症状近端DVT的发生率均较低，临床医生在抉择是否抗凝时应充分考虑患者的危险因素。

关键词: 膝, 关节镜, 抗凝药, 静脉血栓形成, Meta分析

Objective

To evaluate the preventive effect of anticoagulant on venous thromboembolism after knee arthroscopy.

Methods

Five databases including PubMed, Excerpta Medica Database(EMbase), Cochrane Library, China National Knowledge Infrastructure (CNKI) and Wanfang Database were searched. All randomized controlled trials (RCTs) comparing prophylacticuse of anticoagulant drugs and no use of anticoagulant drugs after knee arthroscopywere retrieved from the database establishment to September 2022.Trials involving the use of anticoagulants in the control group or nonpharmacologic anticoagulation in the experimental group were excluded. Two researchers independently screened the literature. The quality of the included literatures was evaluated and data were extracted. The incidence of pulmonary embolism (PE), symptomatic DVT, and asymptomatic proximal DVT of the lower extremities were selected as the observation indicators for efficacy, and the incidence of severe major bleeding and minor bleeding were selected as the observation indicators for safety. RevMan 5.4 software was used for meta-analysis.

Results

Eight RCTS involving 4 302 patients were included. There was no statistically significant difference in the incidence of pulmonary embolism (PE) between the prophylactic anticoagulation group and the non-anticoagulation group after knee arthroscopy [relative risk (RR)=1.36, 95% confidence interval (CI)(0.37, 4.97), P=0.64]. The incidence of symptomatic DVT in prophylactic anticoagulation group was significantly lower than that in non-anticoagulation group[RR=0.32, 95%CI(0.16, 0.63), P=0.001]. The incidence of asymptomatic proximal DVT in prophylactic anticoagulation group was significantly lower than that in non-anticoagulation group [RR=0.17, 95%CI (0.06, 0.48), P=0.0007]. There was no significant difference in the incidence of major hemorrhage between the two groups [RR=1.44, 95%CI(0.25, 8.14), P=0.68]. The incidence of minor hemorrhage in prophylactic anticoagulation group was higher than that in non-anticoagulation group, and the difference was statistically significant [RR=1.47, 95%CI(1.11, 1.94), P=0.006].

Conclusions

Prophylactic use of anticoagulants after knee arthroscopy can effectively reduce the incidence of symptomatic DVT and asymptomatic proximal DVT without increasing the risk of severe bleeding. However, the incidence of PE, symptomatic DVT and asymptomatic proximal DVT after knee arthroscopy is low regardless of whether anticoagulation is used or not. Clinicians should fully consider the risk factors of patients when deciding whether to take anticoagulation.

Key words: Knee, Arthroscopes, Anticoagulants, Venous thromboembolism, Meta-analysis

图1 文献筛选流程图

Figure 1 Flow diagram of literature screening

表1 纳入文献基本特征

Table 1 Basic characteristics of the included studies

作者Author (年份)(year)	试验组(Treatment group)			对照组(Control group)			疗效评价Efficacy evaluation	安全评价Safety evaluation	随访时间Follow-up period	手术类型Type of surgery	血栓评估Methods for thrombus assessment
作者Author (年份)(year)	例数Case number	年龄(岁)Age	干预措施Intervening methods	例数Case number	年龄(岁)Age	干预措施Intervening methods	疗效评价Efficacy evaluation	安全评价Safety evaluation	随访时间Follow-up period	手术类型Type of surgery	血栓评估Methods for thrombus assessment
戴培俊^[12](2019)	86	－	那屈肝素	91	－	无	①②	－	3个月	非交叉韧带重建	彩超
VanAdrichem^[13](2017)	731	48.1±12.8	那屈肝素或达肝素	720	49.1±12.3	无	①②	④⑤	3个月	非交叉韧带重建	彩超
Camporese^[14](2016)	120	44.9±12.8	利伐沙班	114	45.9±13.9	安慰剂	①②③	④⑤	3个月	交叉韧带重建(6%)	彩超
Kaye(2015)^[15]	66	46.0	阿司匹林	104	43.4	无	①②③	－	4周	交叉韧带重建(14%)	彩超
Camporese^[16](2008)	1 101	－	那屈肝素	660	42.3±14.4	弹力袜	①②③	④⑤	3个月	交叉韧带重建(39%)	彩超
Marlovits^[17](2007)	72	29.9±7.4	依诺肝素	68	30.6±6.9	安慰剂	①②③	④	20 d	交叉韧带重建(100%)	MRV
Michot^[18](2002)	66	42.0±14.7	达肝素	64	46.5±13.2	无	①②③	④⑤	31 d	非交叉韧带重建	彩超/静脉造影
Wirth^[19](2001)	117	37.6±13.0	瑞肝素钠	122	38.5±11.6	无	①②③	④⑤	7~10 d	非交叉韧带重建	彩超

表1 纳入文献基本特征

Table 1 Basic characteristics of the included studies

作者Author (年份)(year)	试验组(Treatment group)			对照组(Control group)			疗效评价Efficacy evaluation	安全评价Safety evaluation	随访时间Follow-up period	手术类型Type of surgery	血栓评估Methods for thrombus assessment
作者Author (年份)(year)	例数Case number	年龄(岁)Age	干预措施Intervening methods	例数Case number	年龄(岁)Age	干预措施Intervening methods	疗效评价Efficacy evaluation	安全评价Safety evaluation	随访时间Follow-up period	手术类型Type of surgery	血栓评估Methods for thrombus assessment
戴培俊^[12](2019)	86	－	那屈肝素	91	－	无	①②	－	3个月	非交叉韧带重建	彩超
VanAdrichem^[13](2017)	731	48.1±12.8	那屈肝素或达肝素	720	49.1±12.3	无	①②	④⑤	3个月	非交叉韧带重建	彩超
Camporese^[14](2016)	120	44.9±12.8	利伐沙班	114	45.9±13.9	安慰剂	①②③	④⑤	3个月	交叉韧带重建(6%)	彩超
Kaye(2015)^[15]	66	46.0	阿司匹林	104	43.4	无	①②③	－	4周	交叉韧带重建(14%)	彩超
Camporese^[16](2008)	1 101	－	那屈肝素	660	42.3±14.4	弹力袜	①②③	④⑤	3个月	交叉韧带重建(39%)	彩超
Marlovits^[17](2007)	72	29.9±7.4	依诺肝素	68	30.6±6.9	安慰剂	①②③	④	20 d	交叉韧带重建(100%)	MRV
Michot^[18](2002)	66	42.0±14.7	达肝素	64	46.5±13.2	无	①②③	④⑤	31 d	非交叉韧带重建	彩超/静脉造影
Wirth^[19](2001)	117	37.6±13.0	瑞肝素钠	122	38.5±11.6	无	①②③	④⑤	7~10 d	非交叉韧带重建	彩超

图2 文献质量评估图

Figure 2 Quality assessment chart of the literatures

图3 两组患者膝关节镜术后PE(肺栓塞)发生率比较

Figure 3 Comparison of the incidence of PE after knee arthroscopy between the two groups

图4 两组患者膝关节镜术后有症状DVT(深静脉血栓)发生率比较

Figure 4 Comparison of the incidence of symptomatic DVT after knee arthroscopy between the two groups

图5 两组患者膝关节镜术后无症状下肢近端DVT(深静脉血栓)发生率比较

Figure 5 Comparison of the incidence of asymptomatic proximal lower extremity DVT after knee arthroscopy between the two groups

图6 两组患者膝关节镜术后严重出血发生率比较

Figure 6 Comparison of the incidence of severe hemorrhage after knee arthroscopy between the two groups

图7 两组患者膝关节镜术后轻微出血发生率比较

Figure 7 Comparison of the incidence of minor hemorrhage after knee arthroscopy between the two groups

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Meta-analysis anticoagulant prevention of thrombosis after knee arthroscopy

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Meta-analysis anticoagulant prevention of thrombosis after knee arthroscopy