一项多发性骨髓瘤患者应用免疫调节药物致静脉血栓事件危险因素和预防情况的回顾性研究

A retrospective study of risk factors and current prevention situation of venous thrombosis induced by immunomodulatory drugs in patients with multiple myeloma

目的亚洲多发性骨髓瘤(MM)患者使用免疫调节药物致静脉血栓事件流行病学与欧美人群有着显著差异,是否需要及给予何种血栓预防方案仍存在争议。本研究旨在研究中国MM患者使用免疫调节药物致静脉血栓事件的发生率和危险因素,以期为临床制定血栓预防方案提供参考。方法收集2017年1月至2019年2月在我院接受免疫调节药物(沙利度胺或来那度胺)治疗的多发性骨髓瘤患者的临床资料,包括基本人口学特征、基线实验室检查结果、合并用药和是否出现静脉血栓栓塞症(VTE)并进行统计分析,评估VTE事件发生率并探讨VTE事件相关危险因素。结果185例MM患者被纳入研究,其中5例患者出现VTE事件(发生率2.70%),包括肺栓塞1例和下肢静脉血栓4例。经Logistic回归分析基本人口学特征、基线实验室检查结果、合并用药等多项指标,未发现免疫调节药物致静脉血栓事件的危险因素。通过肿瘤患者VTE风险评估模型对患者进行血栓风险分层,136例高风险状态患者根据指南推荐应予以低分子肝素或华法林抗凝,实际预防性应用低分子肝素及华法林的患者分别为5例及10例,单独使用阿司匹林预防血栓的患者高达159例。出现VTE事件的5例患者均为VTE高风险状态,其中1例未予任何预防措施,其余4例皆使用阿司匹林单药预防,均未按指南推荐合理给予预防用药,提示MM患者普遍存在血栓预防措施不足。高风险状态患者按指南推荐预防用药的VTE发生率为0,仅予阿司匹林的发生率为3.4%,未予任何预防用药的发生率高达33.3%。结论本研究验证了亚洲MM患者VTE事件的发生率显著低于欧美国家,但VTE事件为免疫调节药物最常见的不良反应之一,可影响患者预后,仍应给予血栓预防以足够的重视。有必要积累更多数据来建立中国MM患者VTE事件风险评估模型,为制定针对中国患者的VTE预防指南提供参考。

Objective The epidemiology of venous thrombosis events caused by immunomodulatory drugs in patients with multiple myeloma(MM)in Asia is significantly different from that in Europe and the United States,and it is still controversial whether and what kind of thromboprophylaxis is needed.The purpose of our study is to investigate the incidence and risk factors of venous thrombosis caused by immunomodulatory drugs in Chinese MM patients in order to provide reference for the establishment of thrombosis prevention regimen.Methods Clinical data were retrieved from MM patients who received immunomodulatory drugs(thalidomide or lenalidomide)in our hospital between January 2017 and February 2019,including basic demographic characteristics,baseline laboratory examination results,combined medication and the presence of venous thromboembolism(VTE).The incidence of VTE was evaluated and related risk factors were discussed.Results 185 MM patients were included in the study,among which five(2.70%)occurred VTE events,including one case of pulmonary embolism and four cases of lower extremity venous thrombosis.After logistic regression analysis of basic demographic characteristics,baseline laboratory examination results,combined medication and other indicators,no risk factor was found of venous thrombosis caused by immunomodulators.According to the VTE risk assessment model for cancer patients,136 patients with high risk status were recommended to be anticoagulant with low molecular weight heparin or warfarin according to the guidelines,but actually only 5 patients and 10 patients were respectively treated with low molecular weight heparin and warfarin as prophylaxis,and 159 patients were treated with aspirin alone to prevent thrombosis.Five patients with VTE events were all in high-risk status,one of them did not get any preventive measures,and the other four received aspirin alone.None of them were reasonably given preventive drugs as recommended by the guidelines,suggesting that there were generally insufficient preventive measures for thrombosis in MM patients.For highrisk patients,the incidence rate of VTE was 0 in those treated with guideline-recommended prophylaxis,and 3.4%in those with aspirin alone,but 33.3%in those with no prophylaxis.Conclusion This study verified that the incidence of VTE in Asia MM patients was significantly lower than that in European and American countries.As one of the most common adverse reactions of immunomodulatory drugs,VTE can affect the prognosis of patients,so enough attention should be paid to the prevention of venous thrombosis.It is necessary to accumulate more data to establish the risk assessment model of VTE events in Chinese MM patients,so as to provide reference for the development of VTE prevention guidelines for Chinese patients.