He X H, Zhu Q L, Yuan Y H, Long X D, Xia X H, Wang S, Hu C
Department of Children's Cardiovascular Disease, Hunan Provincial People's Hospital, Changsha 410005, China.
Department of Ultrasoud, Hunan Provincial People's Hospital, Changsha 410005, China.
Zhonghua Er Ke Za Zhi. 2021 Feb 2;59(2):95-100. doi: 10.3760/cma.j.cn112140-20200719-00737.
To investigate the safety of warfarin for Kawasaki disease (KD) with coronary artery aneurysm (CAA) and its prognosis. Twenty one children with KD complicated with giant CAA, multiple CAA in one coronary artery or thrombosis in coronary artery were enrolled in this prospective study. Warfarin was used to control the goal international normalized ratio (INR) ranging from 2.0 to 3.0. The CAA diameter, number, location and thrombus in coronary artery were recorded at the beginning of treatment, 1, 2, 3, 4 weeks and 2, 3, 6, 12 months after treatment, as well as the influence on INR, electrocaroliogram, creatine kinase-MB (CK-MB), troponin I. Standardized warfarin bleeding risk training and management was implemented. Children were divided into implementation group and non-implementation group according to the status of actual implementation of their parents. The incidence of bleeding events was compared between the two groups. Comparisons between groups were performed using a Rank sum test and a Fisher exact test. In the 21 patients (15 males and 6 females), the age of onset ranged from 2 months to 6 years. There were 4 cases with grade Ⅱ, 7 cases with grade Ⅲ, 7 cases with grade Ⅳ and 3 cases with grade Ⅴ according to the severity of coronary arterial lesions before treatment. The time of clinical detection of thrombus in 10 children with thrombosis ranged from the fourth day to the fourth month. The dose distribution of warfarin was 0.06-0.10 mg/(kg·d), and the INR was 1.80-2.59. Among the 10 cases with thrombus, 8 cases had disappearance of thrombi and 2 cases with grade Ⅴ had thrombus organization to different degree. After treatment, the coronary artery ectasia of the 4 cases with grade Ⅱ all returned to normal. Among the 7 cases with grade Ⅲ, 3 cases of coronary artery aneurysms returned to normal, and 4 cases did not change. Among the 7 cases with grade Ⅳ , 5 cases of coronary artery aneurysms shrank to grade Ⅲ, and 2 cases remained unchanged. Three cases with grade Ⅴ lesions had no changes in aneurysm. Neither new thrombus nor new CAA was detected during the treatment. There was no significant change in electrocardiogram before and after treatment. No statistically significant difference was found regarding the troponin I (0.07 (0-3.01) 0.04 (0-0.29) μg/L, =0.932, >0.05) and CK-MB (20.6 (11.2-58.2) . 29.0 (16.7-47.0) U/L, =1.906, >0.05) before and after treatment. The incidence of bleeding events in the implementation group was significantly lower than that in the non-implementation group (2/15 . 4/6, Fisher=5.689, =0.031). The application of goal INR of 2.0-3.0 and adjustment of warfarin dose according to the severity of CAA combined with standardized and strict warfarin bleeding risk training and management, can increase the safety of warfarin therapy in children with KD, improve the prognosis of coronary artery lesions, promote the dissolution of thrombi, prevent new thrombosis, and effectively reduce the incidence of bleeding complication.
探讨华法林用于川崎病(KD)合并冠状动脉瘤(CAA)的安全性及其预后。本前瞻性研究纳入21例KD合并巨大CAA、单支冠状动脉多发CAA或冠状动脉血栓形成的患儿。使用华法林将国际标准化比值(INR)控制在2.0至3.0之间。记录治疗开始时、治疗后1、2、3、4周以及2、3、6、12个月时的CAA直径、数量、位置及冠状动脉内血栓情况,以及对华法林、心电图、肌酸激酶同工酶(CK-MB)、肌钙蛋白I的影响。实施标准化的华法林出血风险培训与管理。根据患儿家长实际实施情况将患儿分为实施组和未实施组,比较两组出血事件发生率。组间比较采用秩和检验及Fisher确切概率法。21例患儿(男15例,女6例),发病年龄2个月至6岁。治疗前根据冠状动脉病变严重程度,Ⅱ级4例,Ⅲ级7例,Ⅳ级7例,Ⅴ级3例。10例有血栓形成的患儿临床发现血栓时间为发病后第4天至第4个月。华法林剂量分布为0.06 - 0.10 mg/(kg·d),INR为1.80 - 2.59。10例有血栓形成的患儿中,8例血栓消失,2例Ⅴ级患儿血栓不同程度机化。治疗后,4例Ⅱ级冠状动脉扩张患儿均恢复正常。7例Ⅲ级患儿中,3例冠状动脉瘤恢复正常,4例无变化。7例Ⅳ级患儿中,5例冠状动脉瘤缩小至Ⅲ级,2例无变化。3例Ⅴ级病变患儿动脉瘤无变化。治疗期间未发现新的血栓及新的CAA形成。治疗前后心电图无明显变化。治疗前后肌钙蛋白I(0.07(0 - 3.01)μg/L比0.04(0 - 0.29)μg/L,Z = 0.932,P > 0.05)和CK-MB(20.6(11.2 - 58.2)U/L比29.0(16.7 - 47.0)U/L,Z = 1.906,P > 0.05)差异无统计学意义。实施组出血事件发生率显著低于未实施组(2/15比4/6,Fisher确切概率法P = 5.689,P = 0.031)。应用目标INR 2.0 - 3.0并根据CAA严重程度调整华法林剂量,结合标准化、严格的华法林出血风险培训与管理,可提高华法林治疗KD患儿的安全性,改善冠状动脉病变预后,促进血栓溶解,预防新的血栓形成,并有效降低出血并发症的发生率。