Lewis Bruce E, Wallis Diane E, Hursting Marcie J, Levine Robert L, Leya Fred
Loyola University Medical Center, 2160 South First Ave, Maywood, IL 60153, USA.
Chest. 2006 Jun;129(6):1407-16. doi: 10.1378/chest.129.6.1407.
We investigated the effects of the direct thrombin inhibitor argatroban, patient demographics, and the platelet count on thrombotic risks in heparin-induced thrombocytopenia (HIT), a serious thrombotic condition, to determine if argatroban provides effective antithrombotic therapy in patients with HIT without increasing bleeding.
We retrospectively analyzed thrombotic outcomes in 882 HIT patients (697 patients receiving mean argatroban doses of 1.7 to 2.0 mug/kg/min for 5 to 7 days, plus 185 historical control subjects) from previously reported prospective studies. Time-to-event analyses of our primary end point-a thrombotic composite of death due to thrombosis, amputation secondary to HIT-associated thrombosis, or new thrombosis within 37 days-and the individual components were conducted, with hazard ratios estimated for treatment with and without adjustments for patient age, gender, race, weight, and baseline platelet count.
Argatroban, vs control, significantly reduced the thrombotic composite risk (HIT: hazard ratio, 0.33; 95% confidence interval [CI], 0.20 to 0.54, p < 0.001; HIT with thrombosis: hazard ratio, 0.39; 95% CI, 0.25 to 0.62, p < 0.001), regardless of covariate adjustments. More argatroban-treated patients than control subjects remained thrombotic event free during follow-up, regardless of whether baseline thrombosis was absent (91% vs 73%) or present (72% vs 50%). Argatroban significantly reduced new thrombosis (p < 0.001) and death due to thrombosis (p </= 0.001). Major bleeding was similar between groups (6 to 7%, p = 0.74). Thrombotic risks were 2 times greater in nonwhite than in white patients, 1.7 times greater in female than male patients with HIT and thrombosis, and increased with decreasing weight or platelet count.
Argatroban, vs control, provides effective antithrombotic therapy in patients with HIT, without increasing bleeding. Patients at higher risk for HIT-associated thrombosis include women, nonwhites, and individuals with current HIT-associated thrombosis, lower body weight, or more severe thrombocytopenia.
我们研究了直接凝血酶抑制剂阿加曲班、患者人口统计学特征及血小板计数对肝素诱导的血小板减少症（HIT，一种严重的血栓形成疾病）血栓形成风险的影响，以确定阿加曲班能否在不增加出血风险的情况下为HIT患者提供有效的抗血栓治疗。
我们回顾性分析了来自先前报道的前瞻性研究中的882例HIT患者（697例接受平均剂量为1.7至2.0微克/千克/分钟的阿加曲班治疗5至7天，外加185例历史对照受试者）的血栓形成结局。对我们的主要终点——由血栓形成导致的死亡、HIT相关血栓形成继发的截肢或37天内新发生的血栓形成组成的血栓形成复合终点——及其各个组成部分进行了事件发生时间分析，估计了在调整和未调整患者年龄、性别、种族、体重及基线血小板计数情况下治疗的风险比。
与对照组相比，阿加曲班显著降低了血栓形成复合风险（HIT：风险比，0.33；95%置信区间[CI]，0.20至0.54，p<0.001；伴有血栓形成的HIT：风险比，0.39；95%CI，0.25至0.62，p<0.001），无论协变量调整情况如何。在随访期间，接受阿加曲班治疗的无血栓形成事件的患者比对照组更多，无论基线时有无血栓形成（分别为91%对73%）还是有血栓形成（分别为72%对50%）。阿加曲班显著降低了新发生的血栓形成（p<0.001）和因血栓形成导致的死亡（p≤0.001）。两组间严重出血情况相似（6%至7%，p = 0.74）。非白人患者的血栓形成风险是白人患者的2倍，患有HIT且伴有血栓形成的女性患者的血栓形成风险是男性患者的1.7倍，且血栓形成风险随着体重或血小板计数的降低而增加。
与对照组相比，阿加曲班可为HIT患者提供有效的抗血栓治疗，且不增加出血风险。HIT相关血栓形成风险较高的患者包括女性、非白人以及目前患有HIT相关血栓形成、体重较低或血小板减少更严重的个体。
