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The Severity of Sepsis-Associated Coagulopathy Is Linked With the Amount of Dysfunctional Organs and the Overall Outcome of the Patient FREE TO VIEW

Jean-Francois Mathieu, MS; Sylvie Boucher, BS
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University of Montreal, LaPrairie, QC, Canada

Chest. 2014;146(4_MeetingAbstracts):233A. doi:10.1378/chest.1994662
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SESSION TITLE: Sepsis & Septic Shock Posters

SESSION TYPE: Original Investigation Poster

PRESENTED ON: Wednesday, October 29, 2014 at 01:30 PM - 02:30 PM

PURPOSE: Severe Sepsis(SS)is linked with acute organ dysfunctions.Hemodynamic Instability is the main cause of organ failures.Production of pro-inflammatory cytokines induce a Sepsis-Associated Coagulopathy(SAC),via 3 mechanisms:Activation of Coagulation Cascade,Down-Regulation of Natural Anticoagulants,Inhibition of endogenous fibrinolytic system.The purpose was to see if SAC could lead to Multiple Organ Failure.

METHODS: 74 patients in the ICU with a diagnosis of sepsis,were sreened for these criteria:All-cause mortality during hospital stay,Number of Organs showing an acute Dysfunction(NOD),Hematologic values,including platelets,PT,D-Dimers,fibrinogen,Protein-C(PC),Antithrombin (AT),Calculation of our modified Hemostatic Score(HS):Platelets >100(0 point),50-100(1),< 50(2);Increase of PT in seconds:<3(0),3-6(1),>6(2);D-Dimers:N(0),>N(2),>5 times the upper limit of N(3);PC:N(0),0.50Un/l(1),<0.50Un/l(2);AT:N(0),0.50Un/l(1),< 0.50Un/l(2).

RESULTS: All-cause mortality was 55%(41/74).The 41 patients who died showed a mean NOD of 5.5,compared to the 33 survivors who exhibited an average NOD of 3.5(p<0.001).We have separated the patients in two groups:The first one included patients with a NOD < or=2,showing a low rate of mortality(1/11 or 9%).The second one included patients with a NOD > or=3, with a higher rate of mortality(40/63 or 63%).Both groups were then subdivided,on the basis of PC and AT,as single biomarkers;and HS,as a combination of five hematologic biomarkers.Group 1:Survivors(n=10;mean PC=0.64,AT=0.59,HS=5.6).Dead patient(n=1;PC=0.23,AT=0.27,HS 8.0).Group 2:Survivors(n=23;mean PC=0.48,AT=0.53,HS=7.0).Dead patients(n=40;mean PC=0.34,AT=0.42,HS=9.0).

CONCLUSIONS: International Society on Thrombosis and Hemostasis has developed a scoring system to define DIC.We have deleted fibrinogen,an acute phase reactant,increased in SS.We then added PC/AT,two natural anticoagulants.We wanted to create a new HS,including the 2nd procoagulant mechanism in SS.Data obtained showed a border between 2 and 3 NOD,regarding how severe would be SAC and outcome.

CLINICAL IMPLICATIONS: Recombinant human Activated Protein-C(rhAPC),was withdrawn,because of poor results of PROWESS-SHOCK trial.The main inclusion criterion was hemodynamic(septic shock)while rhAPC has hematologic mechanisms of action.Patients that benefit most from rhAPC,are those with the worst manifestations of SAC.Further studies are needed,with hematologic inclusion criteria,and 3 or more NOD.Most probably,rhAPC could still help sub-groups of SS patients(eg,with DIC).

DISCLOSURE: The following authors have nothing to disclose: Jean-Francois Mathieu, Sylvie Boucher

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