Orthopedic Injury‐Induced Hypercoagulability in Rats

Abstract

Trauma‐associated hypercoagulability is estimated to occur in 28% of injured patients, leading to thromboembolic complications such as deep venous thrombosis and pulmonary embolism. Orthopedic injury accounts for >45% of injuries requiring hospitalization. However, few clinically relevant models exist to examine the specific mechanisms underlying orthopedic injury‐induced hypercoagulability. Therefore, the aim of this study was to establish a novel rodent model of hypercoagulability after bilateral hindlimb injury mimicking the hypercoagulability found in trauma patients. For this purpose, 16‐week‐old male Wistar rats (n=5, mean body weight=381±21 g) were anesthetized; had carotid catheters placed for serial blood sampling; and were subjected to bilateral hindlimb fibula fracture with controlled soft tissue and muscular crush injury followed by injection of bone homogenate, mimicking injuries sustained with bilateral femur fracture. Blood samples were drawn into 4% sodium citrate, incubated for 30 min at room temperature while rocking, and analyzed by native thromboelastography (TEG) at 3, 6, 12, and 24 h post‐injury. TEG is a viscoelastic assay that allows for comprehensive assessment of clot formation and degradation in whole blood which, unlike standard clinical coagulation tests, can detect hypercoagulability. Baseline TEG studies were performed in triplicate immediately after catheter placement. Compared to baseline measurements, mean TEG parameters did not significantly differ at 3 and 6 h time points. However, significant hypercoagulability was noted at 12 h in maximal amplitude of clot firmness (1.2‐fold increase, p=0.002), overall clot strength (TEG ‘G’ value, 2.1‐fold increase, p=0.003), and thrombin generation (1.2‐fold increase, p=0.003); these parameters remained persistently elevated at 24 h (1.3, 2.5, and 1.2‐fold higher than baseline, respectively; all p<0.003). There were no significant differences compared to baseline at any time points in the TEG parameters R (reflecting time to clot initiation), K or angle (reflecting fibrin polymerization kinetics), or lysis index (reflecting fibrinolysis; all p>0.05). In summary, a rodent model of bilateral hindlimb orthopedic injury recapitulates post‐injury hypercoagulability identified in human trauma patients, as identified by TEG. Hypercoagulability is specifically manifested as increased clot strength and thrombin generation, with no changes alterations in time to clot formation, fibrin polymerization kinetics, or fibrinolysis. We propose that this model will allow for investigation of mechanisms mediating injury‐induced hypercoagulability to assist in identifying novel strategies for thromboprophylaxis.Support or Funding InformationNIH HL105324, NIH HL130577, NIH TR001417, and NIH GM115428This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.