Coagulation system and platelets are fully activated in uncomplicated sepsis

Objective: To test the hypothesis that the coagulation system and platelets are activated in sepsis, the uncomplicated and usually earliest stage of t he septic process, and to compare the findings detected in sepsis with thos e found in severe sepsis and septic shock. Design: Prospective study comparing patients with sepsis, severe sepsis, an d septic shock, and healthy volunteers. Setting: General intensive care unit in a tertiary university hospital. Patients: Seventy-four consecutive septic patients (45 with sepsis, 15 with severe sepsis, and 14 with septic shock). Fourteen healthy volunteers serv ed as control subjects. Intervention: None. Measurements and Main Results:After blood sampling, molecular activation ma rkers of coagulation (prothrombin fragments 1 and 2, fibrinopeptide A, thro mbin-antithrombin complexes, and monomers of fibrin) and of platelets (p-th romboglobulin and platelet factor 4), several coagulation factors, global t ests of coagulation (prothrombin time and activated partial thromboplastin time), and platelet count (PTL) were measured. In sepsis, prothrombin fragm ents 1 and 2, fibrinopeptide A, thrombin-antithrombin complexes, and monome rs of fibrin were increased to 2.52 +/- 0.21 nmol/L, 20.88 +/- 2.52 ng/mL, 33.8 +/- 2.9 mu g/L, and 69% positive, respectively, compared with control subjects (0.86 +/- 063 nmol/L, 1.14 +/- 0.15 ng/mL, 16.07 +/- 1.01 mu g/L, and 0%, respectively). beta-Thromboglobulin and the beta-thromboglobulin-to -platelet factor 4 ratio were also increased to 107.87 +/- 11.87 IU/mL and 8.86 +/- 1.06, compared with controls (18.36 +/- 2.99 IU/mL and 2.67 +/- 0. 52, respectively). With the exception of a decrease in factor XII and an in crease in fibrinogen, coagulation factors, global coagulation tests, and PT L were not changed in sepsis. In severe sepsis and mainly in septic shock, coagulation factors were markedly decreased, global coagulation tests were prolonged, and PTL was reduced. All changes were independent of the causati ve infectious pathogen. Conclusion: Coagulation system and platelets are strongly activated in seps is. In this stage, only factor XII is decreased. In contrast, in severe sep sis and mainly in septic shack, most of the coagulation factors are deplete d, PTL is decreased, and global coagulation tests are prolonged, indicating exhaustion of hemostasis. Finally, Gram-positive, Gram-negative, and other microorganisms produce identical impairment of coagulation.