肿瘤相关静脉血栓栓塞症的防治新认识

New knowledge of prophylaxis and treatment about cancer⁃associated thrombosis

肿瘤相关血栓(cancer-associated thrombosis,CAT)是肿瘤患者的第二大死亡原因,仅次于肿瘤自身进展,并可导致患者住院时间延长和再住院,造成严重的社会医疗负担。JAK2、ALK、KRAS突变等肿瘤特异性基因突变与实体肿瘤患者的CAT风险密切相关。接受免疫检查点抑制剂治疗的患者有很高的CAT风险,1年的累计发病率为10.86%。因此,准确的风险评估至关重要。Khorana评分(Khorana risk score,KRS)是首个评估CAT风险的模型,并已在多项研究中得到验证。新一代模型是基于KRS的升级改良,如Vienna CAT模型、PROTECHT模型、CONKO模型,但尚未经过大规模的外部验证。由于肿瘤与CAT密切相关,国内外制定了多个CAT相关预防指南,均建议肿瘤术后患者接受预防性抗凝治疗。低分子肝素(low molecular weight heparin,LMWH)是最广泛用于预防CAT的抗凝药物,新型口服抗凝药物(new oral anticoagulants,NOAC)亦被用于CAT预防。预防性抗凝治疗虽有导致大出血发生率增加的风险,但患者总体获益大于风险。治疗CAT的策略复杂,NOAC可作为非消化道肿瘤患者的一线药物,而胃肠道肿瘤患者抗凝首选LMWH。由于CAT患者同时接受抗凝治疗与抗肿瘤治疗,故需考虑药物间的相互作用,注意避免药物所致的出血,尤其是联合用药对NOAC药代动力学的影响。目前尚不明确CAT抗凝治疗的最佳持续时间,指南均建议CAT初发患者完成3~6个月抗凝治疗后,应继续接受无限期的抗凝。医师在确定肿瘤患者的抗凝疗程时,应评估血栓复发风险、出血风险,优化治疗方案。

Cancer-associated thrombosis(CAT)is the second leading cause of death in cancer patients,second only to the progression of the tumor.It leads to extended hospitalization and re-hospitalization,resulting in a serious social medical burden.Tumor-specific gene mutations such as JAK2,ALK,and KRAS mutations are closely related to the risk of CAT in patients with solid tumors.Patients treated with immune checkpoint inhibitors have a high risk of CAT,with a 1-year cumulative incidence rate of 10.86%.Therefore,accurate risk assessment is important.The Khorana risk score(KRS)is the first model to assess CAT risk and has been validated in several studies.The new generation models are based on the improvement of KRS,but they have not yet undergone large-scale external verification,such as the Vienna CAT model,PROTECHT model,and CONKO model.Due to the strong correlation between tumors and CAT,several CAT-related prevention guidelines have been established domestically and abroad.All of these guidelines recommend that patients undergo preventive anticoagulation therapy after tumor surgery.Low molecular weight heparin(LMWH)is the most widely used anticoagulant drug to prevent CAT.New oral anticoagulants(NOAC)are also used to prevent CAT,despite the incidence of hemorrhaging increases,the overall benefits to patients outweigh the risks.The strategy for treating CAT is complex.For patients with non-gastrointestinal tumors,NOAC can be used as a first-line drug,while LMWH is recommended for anticoagulation in patients with gastrointestinal tumors.Since CAT patients receive anticoagulation and anti-tumor therapy at the same time,drug interactions need to be considered to avoid drug-induced bleeding,especially the impact of combined medication on NOAC pharmacokinetics.The ideal length of anticoagulation therapy for CAT remains unclear.Guidelines recommend that patients with CAT should indefinitely continue the anticoagulation therapy after completing 3 to 6 months of ini-tial anticoagulation therapy.Therefore,when determining the course of anticoagulation therapy for cancer patients,physicians should evaluate the risk of recurrence of thrombosis and bleeding,and optimize the treatment plan.