Evaluation of sepsis-induced coagulopathy in critically ill patients

Zbog interakcije upalnog odgovora i koagulacijske kaskade, poremećaji koagulacijskog sustava su česta komplikacija sepse. Kliničke manifestacije obuhvaćaju širok spektar hemostatskih promjena koje variraju od suptilnih oblika koagulopatija do fulminantne diseminirane intravaskularne koagulacije (DIC). Specifična karakteristika sepsom inducirane koagulopatije (SIC) je pretjerana aktivacija koagulacijskih procesa uz izraženu supresiju fibrinolize. Tri patogenetska elementa su ključna kod nastanka DIC-a u sepsi: aktivacija koagulacije, agregacija trombocita i oštećenje vaskularnog endotela. Dodatno, oslabljena je aktivnost antikoagulantnog sustava i suprimirana funkcija fibrinolitičkog sustava. Još uvijek ne postoji zlatni standard u dijagnostičkom postupku SIC-a pa se postavljanje dijagnoze temelji na konvencionalnim laboratorijskim mjerenjima, dijagnostičkim kriteijima za SIC i DIC te viskoelastičnim testovima za praćenje hemostaze. Laboratorijska mjerenja obuhvaćaju klasične koagulacijske pretrage dostupne u većini bolničkih laboratorija: broj trombocita, protrombinsko vrijeme i internacionalni normirajući omjer, razgradne produkte fibrina (FDPs) i fibrinogen. Pad u broju trombocita, produljeno protrombinsko vrijeme, povišene razine FDP-a i smanjene razine fibrinogena su uobičajeni abnormalni nalazi koagulacije koji prate sepsu. Dijagnostički kriteriji su definirani od strane Međunarodnog društva za trombozu i hemostazu (ISTH) i Japanskog udruženja za akutnu medicinu (JAAM), a obuhvaćaju kombinaciju rezultata koagulacijskih testova. Viskoelastični testovi za praćenje hemostaze, kao što su rotacijska tromboelastometrija (ROTEM) i tromboelastografija (TEG), koriste se u dopuni postupka dijagnostike kao indikatori aktivnosti fibrinolitičkog sustava. Iako ne postoji jasno definirano liječenje koagulopatije u sepsi, dostupno liječenje ovisi o fazi bolesti i obuhvaća antikoagulantnu terapiju (nefrakcionirani i niskomolekularni heparin, antitrombin, trombomodulin) u ranijem tijeku bolesti te nadoknadu trombocita i faktora koagulacije ukoliko su nastupile komplikacije vezane uz krvarenje. Budući da se smatra lošim prognostičkim faktorom, rana detekcija SIC-a s odgovarajućom terapijom je cilj evaluacije kritično oboljelih bolesnika sa sepsom.Due to the interaction of the inflammatory response and the coagulation cascade, disorders of the coagulation system are a frequent complication of sepsis. Clinical manifestations include a wide range of hemostatic changes that vary from subtle forms of coagulopathies to fulminant disseminated intravascular coagulation (DIC). A specific characteristic of sepsis-induced coagulopathy (SIC) is excessive activation of coagulation processes with marked suppression of fibrinolysis. Three pathogenetic elements are essential in the development of DIC in sepsis: coagulation activation, platelet aggregation and vascular endothelial cell damage. Additionally, the activity of the anticoagulant system is reduced and the function of the fibrinolytic system is suppressed. There is still no gold standard for diagnosing SIC, so the diagnosis is based on conventional laboratory measurements, diagnostic criteria for SIC and DIC, and viscoelastic hemostatic assays. Laboratory measurements include classic coagulation tests available in most hospital laboratories: platelet count, prothrombin time and international standardizing ratio, fibrin degradation products (FDPs) and fibrinogen. Thrombocytopenia, prolonged prothrombin time, elevated FDP levels, and decreased fibrinogen levels are common coagulation abnormalities accompanying sepsis. Diagnostic criteria have been released by the International Society on Thrombosis and Hemostasis (ISTH) and the Japanese Association for Acute Medicine (JAAM) that consists of a combination of coagulation test results. Viscoelastic hemostatic assays, such as rotational thromboelastometry (ROTEM) and thromboelastography (TEG), are used to complement the measurement of fibrinolytic system activity. Although there is no clearly defined management for septic coagulopathy, available treatment depends on the stage of the disease and includes anticoagulants (unfractionated and low-molecular-weight heparin, antithrombin, thrombomodulin) in the earlier course of the disease and replenishment of platelets and coagulation factors if complications related to bleeding have occurred. As it is a poor prognostic factor, early detection of SIC with appropriate therapy is the goal of the evaluation of critically ill patients with sepsis