Comparative response of platelet fV and plasma fV to activated protein C and relevance to a model of acute traumatic coagulopathy.
Comparative response of platelet fV and plasma fV to activated protein C and relevance to a model of acute traumatic coagulopathy.
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DOI：
10.1371/journal.pone.0099181
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Cap AP
中科院分区：
文献类型：
--
作者：
Campbell JE;Meledeo MA;Cap AP
急性创伤性凝血功能障碍（ATC）与活化蛋白C （aPC）从健康个体的40 pM增加到175 pM有关。aPC主要通过裂解活性凝血因子Va （fVa）发挥其活性。据报道，血小板具有比血浆fVa更能抵抗aPC切割的fVa；这项工作检验了在aPC升高的情况下正常血小板足以维持凝血的假设。对正常血浆、fV缺陷血浆（fVdp）和fVdp中分离的正常血小板进行凝血反应：凝血酶原（PT）试验、浊度测定和血栓弹性成像（TEG），包括aPC对样品的剂量反应。PT和浊度测定表明，正常血浆对aPC的耐药剂量远高于ATC。此外，洗涤正常血小板的平均生理数量（200,000个血小板/mm3）足以消除aPC高达10 nM的抗凝作用，比ATC浓度甚至人重组aPC的稳态药理学浓度高出近两个数量级。aPC在有或没有血小板的正常血浆样品中对凝块溶解也没有显著影响。尽管在静态模型中，血小板fVa对aPC的抵抗略优于血浆fVa，但在ATC或药理学递送的aPC模拟中，fVa都不能充分劈裂以降低凝血参数。aPC可能是ATC的相关指标，也可能与ATC中产生的其他改变活性的产物协同作用。
Acute traumatic coagulopathy (ATC) has been linked to an increase in activated protein C (aPC) from 40 pM in healthy individuals to 175 pM. aPC exerts its activity primarily through cleavage of active coagulation factor Va (fVa). Platelets reportedly possess fVa which is more resistant to aPC cleavage than plasma fVa; this work examines the hypothesis that normal platelets are sufficient to maintain coagulation in the presence of elevated aPC. Coagulation responses of normal plasma, fV deficient plasma (fVdp), and isolated normal platelets in fVdp were conducted: prothrombin (PT) tests, turbidimetry, and thromboelastography (TEG), including the dose response of aPC on the samples. PT and turbidimetric assays demonstrate that normal plasma is resistant to aPC at doses much higher than those found in ATC. Additionally, an average physiological number of washed normal platelets (200,000 platelets/mm3) was sufficient to eliminate the anti-coagulant effects of aPC up to 10 nM, nearly two orders of magnitude above the ATC concentration and even the steady-state pharmacological concentration of human recombinant aPC, as measured by TEG. aPC also demonstrated no significant effect on clot lysis in normal plasma samples with or without platelets. Although platelet fVa shows slightly superior resistance to aPC's effects compared to plasma fVa in static models, neither fVa is sufficiently cleaved in simulations of ATC or pharmacologically-delivered aPC to diminish coagulation parameters. aPC is likely a correlative indicator of ATC or may play a cooperative role with other activity altering products generated in ATC.
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DOI：
10.1097/ta.0b013e318169cd3c
发表时间：
2008-05-01
影响因子：
--
作者：
Brohi, Karim;Cohen, Mitchell J.;Pittet, Jean-Francois
通讯作者：
Pittet, Jean-Francois
影响因子：
20.3
作者：
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通讯作者：
Castoldi, Elisabetta
影响因子：
64.8
作者：
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通讯作者：
Ginsburg, D
影响因子：
6.5
作者：
Cushman, M;Costantino, JP;Krag, DN
通讯作者：
Krag, DN
影响因子：
--
作者：
Bravo MC;Orfeo T;Mann KG;Everse SJ
通讯作者：
Everse SJ