Validation of rotation thrombelastography in a model of systemic activation of fibrinolysis and coagulation in humans.
BACKGROUND
Thrombelastography (TEG) is a whole blood assay to evaluate the viscoelastic properties during blood clot formation and clot lysis. Rotation thrombelastography (e.g. ROTEM) has overcome some of the limitations of classical TEG and is used as a point-of-care device in several clinical settings of coagulation disorders. Endotoxemia leads to systemic activation of the coagulation system and fibrinolysis in humans.


OBJECTIVE
We validated whether ROTEM is sensitive to endotoxin induced, tissue factor-triggered coagulation and fibrinolysis and if its measures correlate with biohumoral markers of coagulation and fibrinolysis.


METHODS
Twenty healthy male volunteers participated in this randomized placebo-controlled trial. Volunteers received either 2 ng kg(-1) National Reference Endotoxin or saline.


RESULTS
Endotoxemia significantly shortened ROTEM clotting time (CT) by 36% (CI 0.26-0.46; P < 0.05) with a strong inverse correlation with the peak plasma levels of prothrombin fragments (F(1 + 2)) (r = -0.83, P < 0.05). Additionally, endotoxin infusion enhanced maximal lysis (ML) 3.9-fold (CI: 2.5-5.2) compared with placebo or baseline after 2 h (P < 0.05). Peak ML and peak tissue plasminogen activator (t-PA) values correlated excellently (r = 0.82, P < 0.05). ROTEM parameters clot formation time and maximal clot firmness were not affected by LPS infusion, whereas platelet function analyzer (PFA-100) closure times decreased.


CONCLUSIONS
Rotation thrombelastography (ROTEM) detects systemic changes of in vivo coagulation activation, and importantly it is a point of care device, which is sensitive to changes in fibrinolysis in humans. The ex vivo measures CT and ML correlate very well with established in vivo markers of coagulation activation (F(1 + 2)) and fibrinolysis (t-PA), respectively.
Spiel
A O
AO
Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
Mayr
F B
FB
Firbas
C
C
Quehenberger
P
P
Jilma
B
B
D000328:Adult; D001777:Blood Coagulation / Q000187:drug effects; D019446:Endotoxemia / Q000097:blood; D005342:Fibrinolysis / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000633:toxicity; D008297:Male; D008954:Models, Biological; D010976:Platelet Count; D013916:Thrombelastography / Q000295:instrumentation / Q000379:methods* / Q000706:statistics & numerical data; D014841:von Willebrand Factor / Q000378:metabolism
D008070:Lipopolysaccharides; D014841:von Willebrand Factor