Abstract | BACKGROUND: Postinjury hypercoagulability occurs in >25% of injured patients, increasing risk of thromboembolic complications despite chemoprophylaxis. However, few clinically relevant animal models of posttraumatic hypercoagulability exist. We aimed to evaluate a rodent model of bilateral hindlimb injury as a preclinical model of postinjury hypercoagulability. METHODS: RESULTS: Injured rats became hypercoagulable relative to baseline by 6 hours based on thromboelastography maximal amplitude (MA) and G (p < 0.005); sham rats became hypercoagulable to a lesser degree by 24 hours (p < 0.005). Compared with sham animals, injured rats were hypercoagulable by MA and G within 6 hours of injury, remained hypercoagulable by MA and G through at least 24 hours (all p < 0.01), and showed impaired fibrinolysis by taurocholic acid LY30 at 12 hours (p = 0.019) and native LY30 at 24 hours (p = 0.045). In terms of antifibrinolytic mediators, α-2 antiplasmin was elevated in trauma animals at 24 hours (p = 0.009), and plasminogen activator inhibitor 1 was elevated in trauma animals at 6 hours (p = 0.004) and 12 hours (p < 0.001) when compared with sham. CONCLUSIONS: Orthopedic injury in rodents induced platelet and overall hypercoagulability within 6 hours and fibrinolytic impairment by 12 to 24 hours, mimicking postinjury hypercoagulability in injured patients. This rodent model of orthopedic injury may serve as a preclinical testing ground for potential therapies to mitigate hypercoagulability, maintain normal fibrinolysis, and prevent thromboembolic complications.
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Authors | Kristen T Carter, Ana C Palei, Frank T Spradley, Brycen M Witcher, Larry Martin, Robert L Hester, Matthew E Kutcher |
Journal | The journal of trauma and acute care surgery
(J Trauma Acute Care Surg)
Vol. 89
Issue 5
Pg. 926-931
(11 2020)
ISSN: 2163-0763 [Electronic] United States |
PMID | 32890345
(Publication Type: Journal Article)
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Chemical References |
- Plasminogen Activator Inhibitor 1
- Serpine1 protein, rat
- alpha-2-Antiplasmin
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Topics |
- Animals
- Disease Models, Animal
- Fibrinolysis
(physiology)
- Hindlimb
(injuries)
- Humans
- Leg Injuries
(blood, complications)
- Male
- Plasminogen Activator Inhibitor 1
(analysis)
- Rats
- Thrombophilia
(blood, etiology, physiopathology)
- alpha-2-Antiplasmin
(analysis)
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