Disturbances of hemostasis in sepsis
Authors:
J. Novotný; M. Penka
Authors‘ workplace:
Oddělení klinické hematologie FN Brno, pracoviště Bohunice, přednosta prof. MUDr. Miroslav Penka, CSc.
Published in:
Vnitř Lék 2012; 58(6): 439-447
Category:
Reviews
Overview
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.
Key words:
sepsis – SIRS – protein C system – disseminated intravascular coagulation – recombinant human activated protein C – drotrecogin α activated
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Diabetology Endocrinology Internal medicineArticle was published in
Internal Medicine
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