title: Influence of resuscitation fluids, fresh frozen plasma and antifibrinolytics on fibrinolysis in a thrombelastography-based, in-vitro, whole-blood model.
abstract: Hyperfibrinolysis has been identified as a mechanism of trauma coagulopathy associated with poor outcome. The aim of the study was to create a trauma coagulopathy model (TCM) with a hyperfibrinolysis thrombelastography (TEG) pattern similar to injured patients and test the effects of different resuscitation fluids and antifibrinolytics on fibrinolysis. TCM was established from whole blood by either 15% dilution with isotonic saline, lactated Ringer's, Plasma-Lyte, 5% albumin, Voluven, Hextend, 6% dextran in isotonic saline or 30% dilution with lactated Ringer's plus Voluven and supplementation with tissue factor and tissue plasminogen activator (tPA). These combinations resulted in a TCM that could then be 'treated' with tranexamic acid (TXA) or 6-aminocaproic acid (ACA). Clot formation was evaluated by TEG. Whole-blood dilution by 15% with crystalloids and albumin in the presence of tissue factor plus tPA resulted in an abnormal TEG pattern and increased fibrinolysis, as did dilution with synthetic colloids. TXA 1 μg/ml or ACA 10 μg/ml were sufficient to suppress fibrinolysis when TCM was diluted 15% with lactated Ringer's, but 3 μg/ml of TXA or 30 μg/ml of ACA were needed for fibrinolysis inhibition induced by simultaneous euvolemic dilution with lactated Ringer's plus Voluven by 30%. A total of 15% dilution of whole blood in the presence of tissue factor plus tPA results in a hyperfibrinolysis TEG pattern similar to that observed in severely injured patients. Synthetic colloids worsen TEG variables with a further increase of fibrinolysis. Low concentrations of TXA or ACA reversed hyperfibrinolysis, but the efficient concentrations were dependent on the degree of fibrinolysis and whole-blood dilution.
authors: Center for Translational Injury Research, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
authors: Vadim
authors: V
authors: Kostousov
authors: Yao-Wei W
authors: YW
authors: Wang
authors: Bryan A
authors: BA
authors: Cotton
authors: Charles E
authors: CE
authors: Wade
authors: John B
authors: JB
authors: Holcomb
authors: Nena
authors: N
authors: Matijevic
mesh_terms: D015119:Aminocaproic Acid / Q000494:pharmacology; D000933:Antifibrinolytic Agents / Q000494:pharmacology*; D001778:Blood Coagulation Disorders / Q000209:etiology; D003102:Colloids; D000077324:Crystalloid Solutions; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D007552:Isotonic Solutions / Q000494:pharmacology*; D008297:Male; D008954:Models, Biological; D019999:Pharmaceutical Solutions / Q000494:pharmacology; D010949:Plasma; D013916:Thrombelastography; D014148:Tranexamic Acid / Q000494:pharmacology; D014947:Wounds and Injuries / Q000150:complications*
chemical_list: D000933:Antifibrinolytic Agents; D003102:Colloids; D000077324:Crystalloid Solutions; D007552:Isotonic Solutions; D019999:Pharmaceutical Solutions; D014148:Tranexamic Acid; D015119:Aminocaproic Acid