HIV replication alters the composition of extrinsic pathway coagulation factors and increases thrombin generation.
HIV replication alters the composition of extrinsic pathway coagulation factors and increases thrombin generation.
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DOI：
10.1161/jaha.113.000264
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发表时间：
2013-07-29
影响因子：
5.4
通讯作者：
INSIGHT SMART Study Team
中科院分区：
文献类型：
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作者：
Baker JV;Brummel-Ziedins K;Neuhaus J;Duprez D;Cummins N;Dalmau D;DeHovitz J;Lehmann C;Sullivan A;Woolley I;Kuller L;Neaton JD;Tracy RP;INSIGHT SMART Study Team
HIV感染导致凝血激活，这可能增加动脉粥样硬化和静脉血栓栓塞性疾病的风险。我们假设HIV复制可能通过改变外源性途径因子来增加凝血功能。在抗逆转录病毒治疗管理策略（SMART）试验的一部分HIV参与者中测量了外部途径因素。使用基于因子组成的经验证的计算建模来估计凝血酶生成。我们通过3项单独的分析来描述抗逆转录病毒疗法（ART）治疗与未治疗状态（艾滋病毒复制）的效果：（1）对接受和未接受ART的患者进行横断面比较（n=717）;（2）推迟与开始ART的随机比较（n=217）;和（3）停止与继续ART的随机比较（n=500）。与病毒抑制相比，HIV复制始终显示某些促凝血剂的短期增加（例如，FVIII升高15%至23%; P<0.001）和关键抗凝剂的降低（例如，抗凝血酶[AT]降低5%至9%和蛋白C降低6%至10%; P<0.01）。HIV复制的净效应是增加凝血潜能（例如，计算模型中凝血酶生成量增加24%至48%; P<0.01）。ART治疗逆转了HIV复制的变化模式，并且在所有3项独立比较中一致。HIV复制导致外在途径因子的复杂变化，其净效应是将凝血潜能增加到可能与临床相关的程度。FVIII和AT变化的关键影响表明，HIV相关凝血异常可能涉及全身性炎症背景下的肝细胞功能变化。URL：ClinicalTrials.gov.唯一标识符：NCT 00027352。
HIV infection leads to activation of coagulation, which may increase the risk for atherosclerosis and venous thromboembolic disease. We hypothesized that HIV replication increases coagulation potentially through alterations in extrinsic pathway factors. Extrinsic pathway factors were measured among a subset of HIV participants from the Strategies for Management of Anti‐Retroviral Therapy (SMART) trial. Thrombin generation was estimated using validated computational modeling based on factor composition. We characterized the effect of antiretroviral therapy (ART) treatment versus the untreated state (HIV replication) via 3 separate analyses: (1) a cross‐sectional comparison of those on and off ART (n=717); (2) a randomized comparison of deferring versus starting ART (n=217); and (3) a randomized comparison of stopping versus continuing ART (n=500). Compared with viral suppression, HIV replication consistently showed short‐term increases in some procoagulants (eg, 15% to 23% higher FVIII; P<0.001) and decreases in key anticoagulants (eg, 5% to 9% lower antithrombin [AT] and 6% to 10% lower protein C; P<0.01). The net effect of HIV replication was to increase coagulation potential (eg, 24% to 48% greater thrombin generation from computational models; P<0.01 for all). The pattern of changes from HIV replication was reversed with ART treatment and consistent across all 3 independent comparisons. HIV replication leads to complex changes in extrinsic pathway factors, with the net effect of increasing coagulation potential to a degree that may be clinically relevant. The key influence of changes in FVIII and AT suggests that HIV‐related coagulation abnormalities may involve changes in hepatocyte function in the context of systemic inflammation. URL: ClinicalTrials.gov. Unique identifier: NCT00027352.