新型口服抗凝药相关白细胞碎裂性血管炎文献病例分析

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目的:分析新型口服抗凝药(NOAC)相关白细胞碎裂性血管炎(LCV)的临床特点。方法:检索PubMed、Embase、ScienceDirect、Ovid、Scopus数据库(截至2020年8月),收集报道NOAC相关LCV的病例报告类文献,提取患者相关信息(性别、年龄、原发病、合并疾病、NOAC应用情况、合并用药情况、LCV发生情况、治疗及转归等)进行描述性统计分析。结果:共收集到NOAC相关LCV患者13例,美国6例,土耳其、西班牙各2例,希腊、南韩、丹麦各1例;男性8例,女性5例;年龄28~95岁,≥60岁者9例;应用阿哌沙班和利伐沙班者各5例,达比加群酯3例。7例有NOAC用药剂量记录,均在说明书推荐范围内。12例患者有服用NOAC至发生LCV时间的记录,为3~18 d,其中7~10 d者7例。13例患者均出现皮肤病变,表现为紫癜和/或皮疹,累及四肢和躯干者4例、下肢7例、下肢和躯干1例、上肢和躯干1例。12例患者进行了病变部位皮肤活检,11例出现中性粒细胞浸润,1例仅出现嗜酸粒细胞浸润。诊断LCV后,13例患者均停服在用NOAC,其中12例换用其他抗凝药,9例接受糖皮质激素治疗;8例LCV痊愈,5例症状改善。结论:NOAC相关LCV多发生在用药7~10 d,主要临床表现为紫癜和皮疹,多累及下肢;停用可疑药物,视病情给予糖皮质激素治疗,预后良好。“,”Objective:To analyze the clinical characteristics of novel oral anticoagulants (NOAC)-related leukocytoclastic vasculitis (LCV).Methods:PubMed, Embase, ScienceDirect, Ovid, and Scopus databases were searched as of August 2020 and case reports on NOAC-related LCV were collected. Relevant information in patients including gender, age, primary disease, co-existing disease, NOAC application, combined medication, LCV occurrence, treatment and outcome of LCV, and etc. was extracted and analyzed using descriptive statistical method.Results:A total of 13 patients were collected; 6 were from the United States, 2 from Turkey, 2 from Spain, and 3 from Greece, South Korea, and Denmark, respectively. There were 8 males and 5 females, aged 29 to 95 years, and 9 patients were ≥60 years old. Apixaban was applied in 5 patients, rivaroxaban in 5 patients, and dabigatran etexilate in 3 patients. Dose of NOAC was recorded in 7 patients, all of which were within the recommended range of the instructions. Time from taking NOAC to the occurrence of LCV was recorded in 12 patients, ranging from 3-18 days (7-10 days in 7 patients) after the first medication. All 13 patients developed skin lesions, presenting as purpura and/or rash. Skin lesions involved limbs and trunk in 4 patients, lower limbs in 7 patients, lower limbs and trunk in 1 patient, and upper limbs and trunk in 1 patient. Twelve patients underwent skin biopsy at the lesion site; 11 patients had neutrophil infiltration and 1 had only eosinophil infiltration. NOAC was stopped in all the 13 patients after diagnosis of LCV. Among them, other anticoagulants were switched in 12 patients and glucocorticoids were given in 9 patients. Finally, 8 were cured and 5 were improved.Conclusions:NOAC-related LCV usually occurred 7-10 days after the first medication, mainly manifested as purpura and rash and often involved the lower extremities. The prognosis was good after drug withdrawal and appropriate application of glucocorticoid according to patient conditions.
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