title: Coagulation phenotypes in septic shock as evaluated by calibrated automated thrombography.
abstract: Sepsis induces alterations of coagulation suggesting both hypercoagulable or hypocoagulable features. The result of their combination remains unknown, making it difficult to predict whether one prevails over the other. Thrombin generation tests (TGTs) stand as an interesting tool to establish an integrative phenotype of coagulation. It has been reported that septic patients display a hypocoagulable trait using TGT. However, protein C (PC) system response was not evaluated. We aimed at describing the thrombin generation profile in patients with septic shock under conditions that are sensitive to PC system to evaluate the net results of coagulation abnormalities and to determine whether hypercoagulable or hypocoagulable traits coexist within a given individual. Thrombin generation was studied in plasma from patients presenting with septic shock at diagnosis and 6 h after a conventional therapeutic management using calibrated automated thrombography with or without thrombomodulin (TM) addition. Patients exhibit clear alterations of TGT that present as both consumption-related hypocoagulability (evidenced without TM addition) but also hypercoagulability by decreased sensitivity to the PC system evidenced with TM addition. No difference could be demonstrated between survivors and nonsurvivors at Day 28, but patients who do not respond to therapeutics at 6 h seem to be more hypercoagulable. More importantly, if our results evidence heterogeneity between patients, we show that alterations of coagulation result in an equilibrium in the majority of patients, thus suggesting "normocoagulability"; but, in the presence of a biological imbalance between baseline thrombin generation and sensitivity to TM, the global effect mostly tends toward hypercoagulability. Thus, TGT may help identify distinct biological coagulation phenotypes in the complex alterations induced by sepsis.
authors.affiliation: *Inserm U 1116, Groupe Choc, Equipe 2, Faculté de Médecine, Vandoeuvre les Nancy, France; †University Hospital Ambroise Paré, Intensive Care unit, Section Thorax-Vascular disease-Abdomen-Metabolism, Assistance Publique des Hôpitaux de Paris, Boulogne-Billancourt; ‡University Hospital Ambroise Paré, Laboratory of haematology and immunology, Assistance Publique des Hôpitaux de Paris, Boulogne-Billancourt; §CHU Nancy, Service de Réanimation Médicale Brabois; Pôle Cardiovasculaire et Rénimation Médicale, Hôpital Brabois; Vandoeuvre les Nancy, France ¶Univ Paris-Sud, Laboratoire d'hématologie, Châtenay-Malabry Cedex; and **Faculté de Médecine Paris Ile de France Ouest, Université Versailles Saint Quentin en Yvelines, Versailles, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Perrin
authors.forename: Cyril
authors.initials: C
authors.lastname: Charron
authors.forename: Jean-Hugues
authors.initials: JH
authors.lastname: François
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Cramer-Bordé
authors.forename: Bruno
authors.initials: B
authors.lastname: Lévy
authors.forename: Delphine
authors.initials: D
authors.lastname: Borgel
authors.forename: Antoine
authors.initials: A
authors.lastname: Vieillard-Baron
mesh_terms: D000368:Aged; D001777:Blood Coagulation; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011486:Protein C / Q000378:metabolism*; D012772:Shock, Septic / Q000097:blood / Q000401:mortality / Q000628:therapy; D015996:Survival Rate; D013918:Thrombin Time / Q000295:instrumentation / Q000379:methods; D018180:Thrombomodulin / Q000378:metabolism; D013997:Time Factors
chemical_list: D011486:Protein C; D018180:Thrombomodulin