Biochemical dynamics relevant to the safety of low-dose, intraclot alteplase for deep vein thrombosis.
Biochemical dynamics relevant to the safety of low-dose, intraclot alteplase for deep vein thrombosis.
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与低剂量血栓内阿替普酶治疗深静脉血栓的安全性相关的生化动力学。
DOI：
10.1016/j.trsl.2012.01.025
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发表时间：
2012-09
期刊：
影响因子：
--
通讯作者：
Horne MK 3rd
中科院分区：
文献类型：
--
作者：
Lozier JN;Cullinane AM;Nghiem K;Chang R;Horne MK 3rd
TPA已被证明是治疗深静脉血栓的有效方法(Radiology 2008；246：619&J VASc Interv Radiol 2011；22：1107)。我们试图将tPA、纤维蛋白原、纤溶抑制剂和D-二聚体的药代动力学与血栓内注射tPA的安全性和有效性联系起来。在一项开放标签研究中，30名受试者通过使用脉冲喷雾导管向血栓内渗透≤10 mg剂量的tPA来接受tPA治疗下肢深静脉血栓。我们在第一次注射tPA后的8小时内测量了各种参数。平均tPA剂量为8.0 mg(SD 1.5 mg)后，tPA平均水平为每毫升75个单位(95%可信区间19-131个单位/毫升)。TPA水平在治疗结束后2小时内恢复到基线水平。PAI-1在tPA治疗后被消耗，但上升到显著高于基线水平(P<；0.001)。纤维蛋白原略有下降，但所有受试者的纤维蛋白原仍为-125 mg/dL。α-2-抗纤溶酶活性在给药后由平均115U/m L降至56U/m L(P<；0.001)，并持续下降8小时。TPA给药后，血浆纤溶酶原浓度立即降至89单位/毫升(P<；0.001)，此后无明显变化。除四名受试者外，所有受试者的D-二聚体水平均为20μg/ml，其中一名受试者是唯一一名未能实现血栓溶解的受试者。低剂量血栓内tPA的安全性是因为它在循环中持续时间短，没有低纤维蛋白原血症，以及反射性升高的PAI-1。D-二聚体保持在20μg/ml的受试者有不能实现溶栓的风险。
Intraclot tPA has been shown to be an effective treatment for DVT (Radiology 2008;246:619 & J Vasc Interv Radiol 2011;22:1107). We sought to correlate pharmacokinetics of tPA, fibrinogen, fibrinolytic inhibitors, and D-dimers with the safety and efficacy of intra-clot tPA. Thirty subjects received intraclot tPA for lower extremity DVT by infiltrating the thrombus with ≤ 10 mg doses tPA in an open-label study, using a pulse-spray catheter. We measured various parameters over 8 hours following a first dose of tPA. Mean tPA levels of 75 units per mL (95% confidence interval 19–131 units/mL) were seen immediately after administration of a mean tPA dose of 8.0 mg (SD 1.5 mg). tPA levels returned to baseline within 2 hours of completion of treatment. PAI-1 was consumed following tPA treatment, but rose to levels significantly greater than baseline (P < 0.001). Fibrinogen decreased slightly, but remained > 125 mg/dL for all subjects. α2-antiplasmin decreased from a mean of 115 units/mL to 56 units/mL after tPA administration (P < 0.001), and remained decreased for 8 hours. Plasminogen at baseline (112 units/mL) decreased to 89 units/mL immediately after tPA administration (P <0.001), and was unchanged thereafter. D-dimer levels were >20 μg/mL in all but four subjects, one of whom was the only one to fail to achieve clot lysis. The safety of low-dose, intra-clot tPA is due to its short persistence in the circulation, lack of hypofibrinogenemia, and a reflexive rise PAI-1. Subjects whose D-dimers remain <20 μg/mL are at risk of not achieving thrombolysis.
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DOI：
10.1016/j.jvir.2011.03.023
发表时间：
2011-08-01
影响因子：
2.9
作者：
Chang, Richard;Horne, McDonald K., III;Lozier, Jay N.
通讯作者：
Lozier, Jay N.
影响因子：
7.5
作者：
Horne, MK;Chang, R
通讯作者：
Chang, R
DOI：
10.1016/j.jvir.2007.03.013
发表时间：
2007-06-01
影响因子：
2.9
作者：
O'Sullivan, Gerard J.;Lohan, Derek G.;Kee, Stephen T.
通讯作者：
Kee, Stephen T.
DOI：
10.1016/j.jvir.2007.10.027
发表时间：
2008-03-01
影响因子：
2.9
作者：
Hilleman, Daniel E.;Razavi, Mahmood K.
通讯作者：
Razavi, Mahmood K.
影响因子：
2.9
作者：
BOOKSTEIN, JJ;VALJI, K
通讯作者：
VALJI, K