基于肝素酶对比试验对COVID-19重型非ICU患者抗凝治疗出血风险的评估与分析

Evaluation and analysis of bleeding risk of anticoagulation therapy in severe non-ICU patients with COVID-19 based on heparinase-modified TEG

目的探讨肝素酶对比试验(heparinase-modified TEG,hmTEG)在评估COVID-19重型非ICU患者凝血状态及抗凝治疗监测中的临床应用效果。方法回顾性分析2022年12月至2023年5月于本院确诊感染新型冠状病毒(SARS-CoV-2)的COVID-19重型非ICU患者临床资料。按依诺肝素初始剂量不同分为治疗剂量组和预防剂量组,通过比较2组患者接受肝素治疗前后,血小板计数、活化部分凝血活酶时间、凝血酶原时间、凝血酶时间、纤维蛋白原、D二聚体、TEG、hmTEG的参数变化,评估COVID-19重型非ICU患者接受不同剂量肝素抗凝后凝血功能的变化及出血风险。结果本研究共纳入179名COVID-19重型非ICU患者,其中治疗剂量组102名,预防剂量组77名。接受肝素抗凝前,除年龄(63.4±11.6 vs 59.8±9.1)D二聚体(678 ng/mL vs 621 ng/mL)和MA值[(69.1±10.2)mm vs(65.6±8.5)mm]外,治疗剂量组血小板计数、活化部分凝血活酶时间、凝血酶原时间、凝血酶时间、纤维蛋白原、R值、K时间、α角、凝血指数(CI),与预防剂量组比较均无统计学差异(P>0.05)。接受肝素抗凝后,治疗剂量组与预防剂量组hmTEG检测结果比较,CKR值[(12.2±4.1)min vs(10.2±3.3)min]、CKHR值[(8.1±3.2)min vs(7.1±2.6)min]差异有统计学意义(P<0.05),其余参数组间差异无统计学意义(P>0.05)。同时,治疗剂量组与预防剂量组比较,肝素残留或过量比例15.69%(16/102)vs 5.19%(4/77)显著增加(P<0.05)。但2组间VTE事件2.35%(2/85)vs 2.78%(2/72)、消化道出血2.35%(2/85)vs 1.39%(1/72)、ICU入住4.71%(4/85)vs 4.17%(3/72)、死亡事件3.53%(3/85)vs 2.78%(2/72)等发生率无差异(P>0.05)。结论在当前COVID-19流行趋势下,COVID-19重型非ICU患者血栓预防的肝素初始剂量选择需更为谨慎,为减少出血事件的发生,采用hmTEG对患者进行出血风险的个体化评估,更有利于肝素剂量的调整和控制。

Objective To investigate the clinical application of heparinase-modified TEG(hmTEG)in evaluating coagulation status and monitoring anticoagulant therapy in severe non-ICU patients with COVID-19.Methods The clinical data of severe non-ICU patients with COVID-19 confirmed to be infected with novel coronary disease(SARS-CoV-2)from December 2022 to May 2023 were analyzed retrospectively.The patients were divided into therapeutic dose group and prophylactic dose group according to the initial dose of enoxaparin.The changes of platelet count,activated partial thromboplastin time,prothrombin time,thrombin time,fibrinogen,D-dimer,TEG and hmTEG before and after heparin treatment were compared between the two groups,so as to evaluate the changes of coagulation function and bleeding risk of COVID-19 severe non-ICU patients after anticoagulation with different doses of heparin.Results A total of 179 severe non-ICU patients with COVID-19 were enrolled in this study,including 102 patients in therapeutic dose group and 77 patients in prophylactic dose group.Before receiving heparin anticoagulation,except for age(63.4±11.6 vs 59.8±9.1)D-dimer(678 ng/mL vs 621 ng/mL)and MA values[(69.1±10.2)mm vs(65.6±8.5)mm],there were no statistical differences in platelet count,activated partial thromboplastin time,prothrombin time,thrombin time,fibrinogen,R value,K time,αangle and coagulation index(CI)between the therapeutic dose group and the prophylactic dose group(P>0.05).After receiving heparin anticoagulation,there were significant differences in CKR value[(12.2±4.1)min vs(10.2±3.3)min]and CKHR value[(8.1±3.2)min vs(7.1±2.6)min]between therapeutic dose group and prophylactic dose group(P<0.05),but no significant differences in other parameters between groups(P>0.05).Meanwhile,the proportion of heparin overdose in the therapeutic dose group was significantly higher than that in the prophylactic dose group 15.69%(16/102)vs 5.19%(4/77)(P<0.05).However,there was no difference in the incidence of VTE events 2.35%(2/85)vs 2.78%(2/72),gastrointestinal bleeding 2.35%(2/85)vs 1.39%(1/72),ICU admission 4.71%(4/85)vs 4.17%(3/72)and death events 3.53%(3/85)vs 2.78%(2/72)between the two groups(P>0.05).Conclusion In the current epidemic trend of COVID-19,in order to reduce the occurrence of bleeding events,the heparin dose should be selected more carefully in the prevention of thrombosis in severe non-ICU patients with COVID-19.The individualized assessment of bleeding risk by hmTEG is more conducive to the adjustment and control of heparin dose.