Thromboelastometry (TEM®) Findings in Disseminated Intravascular Coagulation in a Pig Model of Endotoxinemia

Herbert Schöchl,Soheyl Bahrami,Wolfgang Voelckel,Arthur Schulz,Cristina Solomon,Alexander Hanke,Martijn Van Griensven,Heinz Redl

doi:10.2119/molmed.2010.00159

Abstract

Standard coagulation tests have a low specificity and sensitivity for diagnosing disseminated intravascular coagulation. The aim of this study was to determine whether whole blood thromboelastometry (TEM) detects lipopolysaccharide (LPS)-induced changes in coagulation. Blood samples from 10 pigs were drawn at baseline, before and at the end of LPS infusion and 2, 3, 4 and 5 h after the start of endotoxinemia. Simultaneous to TEM, standard coagulation tests and extended coagulation analysis including tissue plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1) were performed. Endotoxinemia resulted in a significant acceleration of the nonactivated TEM (NATEM) clotting time 2 h after the end of LPS infusion; in contrast, the changes in international normalized ratio and activated partial thromboplastin time suggested delayed initiation of coagulation. NATEM maximum clot firmness (MCF) and fibrin-based thromboelastometry test (FIBTEM)-MCF decreased significantly from baseline until the last time point (from 64.6 ± 7.8 and 35.1 ± 12.8 mm to 52.8 ± 4.6 and 21.4 ± 11.8 mm, respectively; P = 0.01 for both parameters). A sharp, transient increase of t-PA had no effect on maximum lysis in the NATEM test. PAI-1 increased significantly 3 h after the start of LPS infusion, paralleled by a decrease in maximum lysis. In conclusion, TEM was superior to standard coagulation tests in reflecting initial activation of coagulation during endotoxinemia. TEM further suggested consumption of coagulation substrate; at the same time, inhibition of plasminogen activation was accompanied by improved clot stability. Further investigations are necessary to establish the clinical relevance of these findings.

Highlights

Massive infection activates the procoagulant pathway, resulting in disseminated intravascular coagulation (DIC), microthrombosis and organ failure [1,2,3]
Coagulation Tests Endotoxinemia resulted in a significant shortening of the CT 2 h after the end of LPS infusion (P = 0.037 compared with baseline)
The International Society on Thrombosis and Haemostasis established a scoring system to diagnose DIC based on prothrombin time, platelet count, fibrinogen concentration and fibrin-related markers

Summary

Introduction

Massive infection activates the procoagulant pathway, resulting in disseminated intravascular coagulation (DIC), microthrombosis and organ failure [1,2,3]. Diagnosis of DIC is complex because of the lack of specific tests [5]. Routine coagulation analysis such as prothrombin time (PT) and activated partial thromboplastin time (aPTT) are available in most laboratories but have a low specificity and sensitivity for diagnosing DIC [6]. Increased activation of the procoagulant pathway and activation or inhibition of the fibrinolytic system cannot be portrayed accurately by these standard assays [7,8,9,10]. Diverse reagents help to evaluate different aspects of the coagulation and fibri-

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