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阿加曲班治疗肝素诱导的血小板减少症女性患者。

Argatroban therapy in women with heparin-induced thrombocytopenia.

作者信息

Jang Ik-Kyung, Baron Suzanne J, Hursting Marcie J, Anglade Eddy

机构信息

Massachusetts General Hospital, Boston, Massachusetts 02114, USA.

出版信息

J Womens Health (Larchmt). 2007 Jul-Aug;16(6):895-901. doi: 10.1089/jwh.2006.0167.

Abstract

OBJECTIVES

Women have increased risk of developing heparin-induced thrombocytopenia (HIT), a serious, immune-mediated prothrombotic condition, and have a worse prognosis when affected. We compared gender differences for treatment and outcomes in HIT patients administered argatroban therapy.

METHODS

From a multicenter retrospective registry of argatroban-treated patients, we identified females (n = 42) and males (n = 50) with clinically diagnosed HIT who were administered argatroban <or=10 microg/kg/min. Upon diagnosis of HIT, heparin was discontinued. Continuous intravenous argatroban was instituted, adjusted to achieve activated partial thromboplastin times (aPTTs) 1.5-3 times baseline. Between-gender comparisons were made of argatroban dosing, aPTT responses, and clinical outcomes (death, amputation, new thrombosis, major bleeding).

RESULTS

At baseline, females and males were generally well matched, excepting platelet count (medians, 101 x 10(9)/L vs. 170 x 10(9)/L, p = 0.01), with 9 (21%) females and 19 (38%) males having HIT-related thrombosis. Typically, argatroban was initiated and maintained at 1.0-1.1 mug/kg/min for approximately 6 days, irrespective of gender. No differences were detected between females and males in aPTTs during therapy (respective medians, 57.3 vs. 59.5 seconds) or time to therapeutic aPTTs (7.3 vs. 10.3 hours), or platelet count recovery (2.5 vs. 7.4 days). Of patients with available data, 20 of 35 (57%) females and 19 of 35 (54%) males were converted to warfarin. The composite end point of death, amputation, or new thrombosis within 37 days of argatroban initiation occurred in 10 (24%) females and 8 (16%) males (p = 0.43). Within 37 days, 7 (17%) females and 7 (14%) males died (2 while on argatroban), 1 (2%) female required amputation (off argatroban), and 3 (7%) females and 2 (4%) males developed new thrombosis (3 while on argatroban). Major bleeding occurred in 1 (2%) female and 1 (2%) male.

CONCLUSIONS

Argatroban can be used effectively and safely to manage HIT in females, with dosing requirements, aPTT responses, and clinical outcomes comparable to those in men. Future, larger studies are warranted in establishing the unique characteristics of HIT in females.

摘要

目的

女性发生肝素诱导的血小板减少症(HIT)的风险增加,这是一种严重的、免疫介导的促血栓形成疾病,患病后预后较差。我们比较了接受阿加曲班治疗的HIT患者在治疗及预后方面的性别差异。

方法

从一个多中心回顾性登记研究中筛选出接受阿加曲班治疗的患者,确定临床诊断为HIT且阿加曲班给药速度≤10微克/千克/分钟的女性(n = 42)和男性(n = 50)。确诊HIT后,停用肝素。开始持续静脉输注阿加曲班,并进行调整以使活化部分凝血活酶时间(aPTT)达到基线值的1.5 - 3倍。比较了两性之间阿加曲班的给药剂量、aPTT反应及临床结局(死亡、截肢、新发血栓形成、大出血)。

结果

基线时,除血小板计数外(中位数分别为101×10⁹/L和170×10⁹/L,p = 0.01),女性和男性总体匹配良好,9名(21%)女性和19名(38%)男性发生了HIT相关血栓形成。通常,无论性别,阿加曲班均以1.0 - 1.1微克/千克/分钟的速度开始并维持约6天。治疗期间女性和男性的aPTT(中位数分别为57.3秒和59.5秒)、达到治疗性aPTT的时间(7.3小时和10.3小时)或血小板计数恢复时间(2.5天和7.4天)均未检测到差异。在有可用数据的患者中,35名女性中的20名(57%)和35名男性中的19名(54%)转换为华法林治疗。在开始使用阿加曲班后37天内,死亡、截肢或新发血栓形成的复合终点事件在10名(24%)女性和8名(16%)男性中发生(p = 0.43)。在37天内,7名(17%)女性和7名(14%)男性死亡(2名在使用阿加曲班期间),1名(2%)女性需要截肢(停用阿加曲班后),3名(7%)女性和2名(4%)男性发生了新发血栓形成(3名在使用阿加曲班期间)。大出血在1名(2%)女性和1名(2%)男性中发生。

结论

阿加曲班可有效、安全地用于治疗女性HIT,其给药要求、aPTT反应及临床结局与男性相当。未来需要开展更大规模的研究以明确女性HIT的独特特征。

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