新型布尼亚病毒感染患者凝血功能异常及其临床意义

目的探讨新型布尼亚病毒感染后患者发热伴血小板减少症状(SFTS)发病期和恢复期的凝血和血栓相关指标及其临床意义。方法选择2020年4月12日至8月12日在安徽医科大学第一附属医院收治的新型布尼亚病毒感染后SFTS患者,其中SFTS发病期36例,SFTS恢复期18例,并招募36名健康人作为健康对照组,采集血浆标本。回顾性分析血浆凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、纤维蛋白原含量(FIB)、血浆凝血酶时间(TT)、抗凝血酶-Ⅲ(AT-Ⅲ)、纤维蛋白降解产物(FDP)、D-二聚体(D-D)、血栓调节蛋白(TM)、凝血酶-抗凝血酶复合物(TAT)、纤溶酶-α2纤溶酶抑制物复合物(PIC)、组织型纤溶酶原激活剂-抑制剂1复合物(t-PAIC)浓度。统计比较3组间上述指标的差异。结果与健康对照组比较,SFTS发病组PT[12.5(12.1,13.6)s比10.8(10.5,11.5)s,P<0.05]较长,但仍在正常参考值范围内(14.0~21.0 s);APTT[49.1(42.0,58.2)s比28.5(26.6,30.4)s,P<0.05]较长;FDP[6.07(2.67,8.64)μg/ml比1.00(0.80,1.87)μg/ml]和D-D[2.27(1.04,2.98)μg/ml比0.30(0.21,0.47)μg/ml]较高(P均<0.001);血浆TAT[16.05(8.05,26.58)ng/ml比3.55(2.60,4.85)ng/ml]和PIC浓度[4.44(2.52,5.54)μg/ml比0.84(0.60,1.35)μg/ml]较高(P均<0.001);TM[(19.41±8.29)TU/ml比(9.33±1.89)TU/ml]和t-PAIC浓度[(37.52±21.10)ng/ml比(7.06±3.37)ng/ml]较高(P均<0.001)。SFTS恢复组患者血浆中TAT浓度为9.10(3.95,18.40)ng/ml,仍高于正常参考范围(<4 ng/ml),PIC浓度低于SFTS发病组[1.91(1.45,2.93)μg/ml比4.44(2.52,5.54)μg/ml,P<0.05],TM和t-PAIC低于SFTS发病组(P均<0.05)。结论SFTS患者发病期机体凝血系统激活,血管内皮受到损伤;恢复期血管内皮损伤情况减轻,但机体依然存在一定程度的凝血系统障碍,提示当体内病毒清除后,仍需继续监测凝血指标。

Abnormal coagulation activity and the related clinical significance in patients with novel bunyavirus infection

Objective To explore the related indexes of coagulation and thrombosis and their clinical significance in patients with severe fever with thrombocytopenia symptoms(SFTS)during the onset and recovery period after novel bunyavirus infection.Methods A total of 36 patients diagnosed with SFTS(SFTS onset group)and 18 convalescent SFTS patients,who were hospitalized in the First Affiliated Hospital of Anhui Medical University from April 12,2020,to October 12,2020 were recruited in this study.Thirty-six healthy controls were recruited from volunteers.Plasma was collected and prothrombin time(PT),activated partial thromboplastin time(APTT),fibrinogen(FIB),thrombin time(TT),antithrombin-Ⅲ(AT-Ⅲ),fibrin degradation product(FDP)and D-dimer(D-D)were determined by automatic blood coagulation analyzer.Thrombomodulin(TM),thrombin-antithrombin complex(TAT),plasminase-α2 plasminase inhibitor complex(PIC)and tissue plasminogen activator-plasminogen activator inhibitor 1 complex(t-PAIC)were determined by an automatic chemiluminescence analyzer.Results Compared with the healthy control group,PT was significantly prolonged(12.5[12.1,13.6]s,vs 10.8[10.5,11.5]s,P<0.05)in SFTS onset group,but was still within the reference range(14.0-21.0 s),and APTT(49.1[42.0,58.2]s vs 28.5[26.6,30.4]s,P<0.05)was also significantly prolonged in SFTS onset group.Compared with healthy control group,FDP(6.07[2.67,8.64]μg/ml vs 1.00[0.80,1.87]μg/ml,P<0.001),D-D(2.27[1.04,2.98]μg/ml vs 0.30[0.21,0.47]μg/ml,P<0.001),TAT(16.05[8.05,26.58]ng/ml vs 3.55[2.60,4.85]ng/ml,P<0.001),PIC(4.44[2.52,5.54]μg/ml vs 0.84[0.60,1.35]μg/ml,P<0.001),TM([19.41±8.29]TU/ml vs[9.33±1.89]TU/ml,P<0.001),and t-PAIC([37.52±21.10]ng/ml vs[7.06±3.37]ng/ml,P<0.001)values were all significantly higher in the SFTS onset group(all P<0.001).The level of TAT in the SFTS recovery group(9.10[3.95,18.40]ng/ml)was still out of the reference range(<4 ng/ml),while the level of PIC in the SFTS recovery group was lower than in SFTS onset group(1.91[1.45,2.93]μg/ml vs 4.44[2.52,5.54]μg/ml,P<0.05).Compared with SFTS onset group,the levels of TM and t-PAIC were lower in the SFTS recovery group(P<0.05).Conclusions Coagulation system activation and vascular endothelial injury are evidenced in SFTS patients.In the convalescence period,the vascular endothelial injury is recovered,however,there is still a certain degree of coagulation dysfunction,therefore,it is necessary to monitor the coagulation indicator of discharged patients post SFTS.