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Coagulation system and platelets are fully activated in uncomplicated sepsis

Mavrommatis, Antonis C. MD; Theodoridis, Thodoris MD; Orfanidou, Androula MSc; Roussos, Charis MD, PhD; Christopoulou-Kokkinou, Vana MD; Zakynthinos, Spyros MD

Clinical Investigations
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Objective: To test the hypothesis that the coagulation system and platelets are activated in sepsis, the uncomplicated and usually earliest stage of the septic process, and to compare the findings detected in sepsis with those found in severe sepsis and septic shock.

Design: Prospective study comparing patients with sepsis, severe sepsis, and 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 served as control subjects.

Intervention: None.

Measurements and Main Results: After blood sampling, molecular activation markers of coagulation (prothrombin fragments 1 and 2, fibrinopeptide A, thrombin-antithrombin complexes, and monomers of fibrin) and of platelets (β-thromboglobulin and platelet factor 4), several coagulation factors, global tests of coagulation (prothrombin time and activated partial thromboplastin time), and platelet count (PTL) were measured. In sepsis, prothrombin fragments 1 and 2, fibrinopeptide A, thrombin-anti-thrombin complexes, and monomers of fibrin were increased to 2.52 ± 0.21 nmol/L, 20.88 ± 2.52 ng/mL, 33.8 ± 2.9 μg/L, and 69% positive, respectively, compared with control subjects (0.86 ± 063 nmol/L, 1.14 ± 0.15 ng/mL, 16.07 ± 1.01 μg/L, and 0%, respectively). β-Thromboglobulin and the β-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 increase in fibrinogen, coagulation factors, global coagulation tests, and PTL 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 causative infectious pathogen.

Conclusion: Coagulation system and platelets are strongly activated in sepsis. In this stage, only factor XII is decreased. In contrast, in severe sepsis and mainly in septic shock, most of the coagulation factors are depleted, 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.

From the Department of Critical Care and Pulmonary Services (Drs. Mavrommatis, Roussos, Zakynthinos), University of Athens Medical School, and the Hematology Laboratory (Drs. Theodoridis, Orfanidou, Christopoulou-Kokkinou), Evangelismos Hospital, Athens, Greece.

Address requests for reprints to: Spyros Zakynthinos, MD, Critical Care Department, Evangelismos Hospital, 45-47 Ipsilandou St, GR-10675 Athens, Greece.

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