• Dagmar Oberhofer, Nastja Kucisec-Tepes, Jasna Skok, Niksa Vucić, and Kresimir Cala.
• Zavod za anesteziologiju i intenzivno lijecenje, Opće bolnice Sveti Duh, Zagreb, Hrvatska.
• Acta Med Croatica. 2004 Jan 1;58(5):389-94.

AimTo determine whether sequential change in coagulation parameters such as activated partial thromboplastin time (aPTT), prothrombin time (PT), platelets count and fibrinogen level may predict the outcome of patients in sepsis.Study DesignCohort longitudinal study.Patients And MethodsPatients with positive two or more clinical criteria for sepsis were eligible for the study. Thirty patients were included, 24 male and 6 female. Eight patients survived, while 22 deceased. Median age of survivors was 66 years (range 23-77), and in non-survivors it was 69 years (range 48-79), p=0.37. In 9 patients malignancy was an underlying disease. APACHE II score was calculated at admittance, median value for survivors was 10 (range 7-15) and for non-survivors it was 26 (range 6-35), p=0.001. Calculated MODS score at the time blood cultures was 2 (range 0-9) for survivor and 6.5 (range 2-13) for non-survivors, p=0.007. Blood cultures were taken at the onset of sepsis, and in 29 patients they were positive. Coagulation parameters were measured at admittance, at the onset of sepsis and 48 hours after the introduction of the specific antimicrobial therapy.ResultsAnalysis of variance for repeated measurements between survivors and non-survivors has shown that there were no differences in values of coagulation parameters. The only significant difference between these groups of patients was APACHE II and MODS score. In 7 patients with severe thrombocytopenia (<33,000 x 10(9)/L) as a result of irreversible septic shock a clinically visible bleeding was present in only one patient.DiscussionDisseminated intravascular coagulation (DIC) is a clinical-pathological syndrome in which wide-spread intravascular coagulation is induced by procoagulants that are introduced or produced in the blood circulation and overcome the natural anticoagulant mechanisms. DIC causes tissue ischemia from occlusive microthrombi as well as bleeding from both the consumption of platelets and coagulation factors and the anticoagulant effect of products of secondary fibrinolysis. In sepsis, tissue factor which is the most common trigger of DIC can be generated and expressed on membranes of monocytes and endothelial cells during the systemic inflammatory response syndrome (SIRS). The wide-spread generation of thrombi in sepsis induces deposition of fibrin which leads to vessels obstruction and consumption of substantial amounts of haemostatic factors i.e. platelets, fibrinogen, factors V, VIII and others, protein C and antithrombin III (AT III). Intravascular thrombi trigger secretion of tissue plasmin activator (tPA) from endothelial cells which sets of compensatory thrombolysis which may reopen the occluded blood vessels. But byproducts of thrombolysis such as fibrin/fibrinogen degradation products may enhance bleeding by interfering with platelet aggregation, fibrin polymerization and thrombin activity. The typical feature of sepsis is depression of three powerful anticoagulant systems: protein C pathway, AT III pathway and tissue pathway factor inhibitor (TPFI). This sequence of events led us to hypothesize that alterations in coagulation parameters such as PT, aPTT, fibrinogen, platelets count may predict the outcome of disease, as it is well documented that the development of DIC confers prognosis of sepsis. The failure to distinguish survivors from non-survivors by the alteration in the coagulation parameters in this study may be due to a relatively low sample size or to the clinical necessity of an attending physician to substitute the deficient blood or coagulation product.ConclusionThe coagulation parameters PT, aPTT, platelet count and fibrinogen level can not serve as predictors of outcome in patients with sepsis. Further studies including more discerning coagulation parameters: AT III, D-dimer, soluble fibrin monomer, thrombin/antithrombin complex, plasmin/antiplasmin complex, fibrinopeptid A, fibrinopeptid B are necessary to evaluate whether these procoagulant and anticoagulant factors may help in predicting outcome and severity of sepsis.

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