Novotný J, Penka M
Oddelení klinické hematologie FN Brno, pracoviste Bohunice.
Vnitr Lek. 2012 Jun;58(6):439-47.
Immune system and hemostasis are closely bound together. When one of these systems is activated, another is set in motion too. This is especially noticeable in polytraumas, inflammation, shocks etc. The most important activator of immune system and hemostasis is sepsis. In sepsis there is a vigorous stimulation of immune response because of a liberation of a lot of cytokines and proinflammatory molecules. This may lead to an extrem picture of systemic inflammatory response syndrome. In systemic inflammatory response syndrome a downregulation of thrombomodulin and endothelial protein C receptor on the surface of intact endothel may be detected and there is an upregulation of release of the tissue-type plasminogen activator with a switch to plasminogen activator inhibitor 1 release. There is lowering of activated protein C and fibrinolytic activation followed by fibrinolytic inhibition in septic patients. Consequently we can see consumption of coagulation factors, inhibitors (antithrombin, protein C, and tissue factor pathway inhibitor), microangiopatic hemolysis and thrombocytopenia with a picture of disseminated intravascular coagulation in these patients. The diagnosis of disseminated intravascular coagulation is not uniforme in the literature. Expression of tissue factor on monocytes and endothelium may aggravate this "circulus vitiosus" with serious microcirculatory failure in sense of MOF/MODS (mutliorgan failure/multiorgan dysfunction syndrome). The first steps in the therapy of sepsis represent the treatment of cause of sepsis, vigorous hydratation and maintenance of circulation and pulmonary function, glycemic control etc, the prevention and blocking of the undesirable activation of hemostasis and inflammation being equally important. The treatment with minidoses of heparin was implemented in the past and the question, if this therapy is indicated is not answered yet. The clinical studies of the suitability of the treatment with natural inhibitors of hemostasis (antithrombin, recombinant human activated PC or drotrecogin α activated, rhTFPI) were evaluated in the past and are still under way recently. The unequivocal contribution of these therapies was not proven and recombinant human activated PC was even pulled from the worldvide market.
免疫系统和止血功能紧密相连。当其中一个系统被激活时，另一个系统也会随之启动。这在多发伤、炎症、休克等情况中尤为明显。免疫系统和止血功能最重要的激活因素是脓毒症。在脓毒症中，由于大量细胞因子和促炎分子的释放，免疫反应会受到强烈刺激。这可能导致全身炎症反应综合征的极端表现。在全身炎症反应综合征中，可检测到完整内皮表面血栓调节蛋白和内皮蛋白C受体的下调，同时组织型纤溶酶原激活物的释放上调，并转而释放纤溶酶原激活物抑制剂1。脓毒症患者体内活化蛋白C降低且纤溶激活，随后出现纤溶抑制。因此，在这些患者中可看到凝血因子、抑制剂（抗凝血酶、蛋白C和组织因子途径抑制剂）的消耗、微血管病性溶血和血小板减少，并呈现出弥散性血管内凝血的表现。在文献中，弥散性血管内凝血的诊断并不统一。单核细胞和内皮细胞上组织因子的表达可能会加剧这种“恶性循环”，导致多器官功能衰竭/多器官功能障碍综合征意义上的严重微循环衰竭。脓毒症治疗的首要步骤包括治疗脓毒症的病因、积极补液以及维持循环和肺功能、控制血糖等，预防和阻断止血与炎症的不良激活同样重要。过去曾采用小剂量肝素治疗，但该疗法是否适用的问题尚未得到解答。过去曾对使用止血天然抑制剂（抗凝血酶、重组人活化蛋白C或活化的重组人组织因子途径抑制物）进行治疗的适用性进行临床研究，目前仍在进行中。这些疗法的确切作用尚未得到证实，重组人活化蛋白C甚至已从全球市场撤下。
