产科DIC的病理生理学

Pathophysiology of DIC in obstetric disorders
产科DIC的病理生理学
It is important to understand the normal coagulation process in order to characterise the abnormalities observed during DIC.
为了描述DIC的异常特征，理解正常的凝血过程十分重要。

1.The coagulant response begins with exposure of tissue factor (TF) and binding of factor VIIa
to activate factor X for conversion of pro-thrombin to thrombin.[1]
凝血反应始于组织因子（TF）的暴露以及VIIa与Xa结合使凝血酶原转变为凝血酶[1]。

2.Thrombin generation is further propagated through the intrinsic pathway and the explosive
burst of thrombin results in cleavage of fibrinogen into fibrin.[2]
凝血酶通过内源性途径进一步生成，凝血酶的爆发式生成导致了纤维蛋白原裂解为纤维蛋白[2]。

3.Clot formation is homeostatically regulated to achieve the desired haemostatic effect and this
involves a number of regulatory responses that are spatially and temporally differentiated.
血块的形成是自稳性调节而获得理想的止血效果，这涉及了大量的时空特异性的调解节反应。

4.Normal endothelium at the margins of injury switches from thrombin procoagulant to
anticoagulant activity via its binding to the endothelial receptor, thrombomodulin (TM).[3]
伤口边缘的正常内皮通过与内皮受体凝血酶调节蛋白（TM）结合，由促凝变为抗凝[3]。

5.The thrombin–TM complex activates protein C bound to the endothelial protein C receptor
(EPCR).[4]
凝血酶-凝血酶调节蛋白复合物激活结合与内皮蛋白C受体(EPCR)上的蛋白C[4]。

6.The generated activated protein C (APC) degrades activated factor V and VIII with co-factor
support from protein S to inhibit further clot formation.[5]
产生的活化的蛋白C在来自于蛋白S的辅助因子的支持下降解Va 和VIIIa，抑制血块的进一步形成。

7.Other important anticoagulants involved are anti thrombin and tissue factor pathway inhibitor
(TFPI). The former inactivates thrombin and factor Xa whilst TFPI forms a quaternary complex with tissue factor, factor VIIa and Xa to inhibit the cascading effect towards thrombin generation.[6]
涉及的其它的抗凝血物质是抗凝血酶（AT）和组织因子途径抑制剂（TFPI）。

前者灭活凝血酶和Xa，而TFPI与组织因子、VIIa 、Xa形成四聚体抑制凝血酶生成的级联效应。

8.Normal clot formation is followed by its own regulated dissolution. This process of
fibrinolysis involves thrombin-induced tissue plasminogen activator (t-PA) dependent generation of plasmin from plasminogen.[7]
正常的血块形成紧接着自身调节的溶解，这一纤溶过程涉及了凝血酶诱导的组织纤溶酶原激活物（t-PA）依赖的纤溶酶原向纤溶酶的转化。

9.Regula tion of fibrinolysis is mainly through plasminogen activator inhibitor (PAI-1) and
thrombin activatable fibrinolysis inhibitor (TAFI).[8]
纤溶的调节主要通过纤溶酶原激活物抑制剂-1和凝血酶活化的纤溶抑制剂。

10.PAI-2 is also involved physiologically in pregnancy.
纤溶酶原激活物抑制剂-2也涉及了妊娠生理凝血机制。

11.Whilst these protein–protein interactions are key to the formation and regulation of
coagulation, the availability of an assembling surface critically affects the magnitude of the reaction. In vitro, the availability of negatively charged phospholipid surfaces can accelerate the prothrombinase reaction by 250,000-fold.[9]
虽然这些蛋白-蛋白相互作用是凝血形成和调节的关键，但是装配表面的存在也关键性的影响着反应的级别。

在体外，负电性磷脂表面的存在可以使得凝血酶原反应加速250000倍。

12.In vivo, the relevance of this is demonstrated by the observation that factor Xa infusions
alone are not thrombogenic unless co-infused with negatively charged phospholipids.[10]
在体内，除非一同输注负电性磷脂，单独输注Xa因子是不会生成血栓的，显示这种相关性。

13.Increasing the phospholipids content was shown to convert this haemostatic response into
that of DIC.[9]Whilst phosphatidylserine (PS) behaves as a procoagulant phospholipid, phosphatidylethanolamine (PE) enhances APC activity to promote anticoagulation.[11]
增加磷脂的含量使得止血反应转变为DIC。

磷脂酰丝氨酸是促凝血的，而磷脂酰乙醇胺提高了APC的活性，促进抗凝。

14.Central to the development of DIC is the excessive generation of thrombin in vivo. Whilst
thrombin generation is generally dependent on prothrombinase complex assembly on platelet surfaces, cell-free phospholipid can also support such reactions in vivo. [12, 13]
DIC发展的中心是体内凝血酶的过度生成。

凝血酶的生成通常依赖于血小板表面装配的凝血酶原复合物，而游离的磷脂也促进了体内的这些反应。

15.These form as a result apoptosis or damaged cell membranes to externalise the inner leaflet
and expose PS. Microparticles which carry the externalised PS are generally procoagulant and their circulating levels increase in pregnancy.[14]
做为结果，这些形式凋亡或者损伤了细胞膜，使得磷脂双分子层的内叶外化和磷脂酰丝氨酸暴露。

携带外化的脂酰丝氨酸的微粒通常是促凝的，它们的循环水平在妊娠期升高。

16.Of relevance too is the provision of phospholipid surfaces by lipoproteins such as oxidised
low-density lipoprotein and verylow-density lipoprotein (VLDL), the latter of which can increase several fold in DIC.[15, 16]
另一相关是脂蛋白提供的磷脂表面，例如氧化的低密度脂蛋白和极低密度脂蛋白，后者在DIC时增加几倍。

17.In addition, lipoprotein dysregulation can influence thrombin activity through the relative loss
of high-density lipoprotein (HDL) with its anticoagulant-promoting properties.[17]
另外，脂蛋白调节异常可以通过具有抗凝特性的高密度脂蛋白的相对丢失来影响凝血酶的活性。

18.Circulating lipoproteins have been shown to correlate with a higher incidence of
pre-eclampsia.[18]
循环的脂蛋白显示与先兆子痫的发生率有关。

19.Women with pre-eclampsia exhibited three fold increase in VLDL, with significantly lower
HDL concentrations. This imbalance between the pro and anti-coagulant lipoproteins may contribute to endothelial dysfunction and the pathogenesis of pre-eclampsia.
先兆子痫孕妇VLDL浓度升高3倍，HDL浓度显著降低。

这种促凝和抗凝脂蛋白间的失衡导致了内皮的功能异常和先兆子痫的发病机制。

20.Pivotal role of thrombin in the balance between coagulation and fibrinolysis. Normal clotting
begins with the exposure of tissue factor (TF), which enables factor VIIa to activate factor X
and lead to thrombin (IIa) generation.
Thrombin is procoagulant in converting fibrinogen (Fgn) to fibrin but also controls anticoagulation through generation of activated protein C (aPC) to degrade activated factor V and VIII. Clot dissolution to generate fibrin-degradation products (fdp) occurs through thrombin-induced tissue plasminogen activator (tPA) and regulation of fibrinolysis involves activation of thrombin activatable fibrinolysis inhibitor (TAFI). Thrombin is therefore central to the bal ance between pro and anticoagulant functions as well as pro and antifibrinolytic activities. Dotted lines denote inhibition.
凝血酶在凝血和纤溶平衡中起的关键作用。

正常的凝血开始于组织因子（TF）的暴露，TF使得VIIa激活X，并导致凝血酶的生成。

凝血酶在将纤维蛋白原转化成纤维蛋白的过程中是促凝的，但也通过降解Va和VIIIa的激活的蛋白C的生成控制抗凝。

产生纤维蛋白降解产物（fdp）的血块溶解通过凝血酶诱导的组织纤溶酶原激活物发生。

纤溶的调节涉及了TAFI的激活。

因此，凝血酶是促凝和抗凝以及纤溶和抗纤溶功能平衡的中心。

虚线表示抑制。

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