Emotional pain in non-human mammals: from neural circuitry and opioid signaling to dysthymia-like states, grief-like behaviors, and physiological dysregulation.

Venous thromboembolism (VTE), encompassing deep vein thrombosis (DVT) and pulmonary embolism (PE), remains one of the most serious and potentially life-threatening complications following orthopedic trauma surgery []. Patients undergoing major lower-extremity orthopedic procedures—including total hip arthroplasty (THA), total knee arthroplasty (TKA), and hip fracture surgery—are considered among the highest-risk surgical populations for VTE development []. In the absence of pharmacological thromboprophylaxis, rates of venographically detected DVT reach 54% after THA and up to 64% after TKA, while fatal PE has been reported in up to 2.0% of patients undergoing total hip arthroplasty and up to 7.5% of those undergoing hip fracture surgery [,]. Even with contemporary anticoagulant prophylaxis, VTE still occurs in an estimated 4.4% of patients undergoing major arthroplasty procedures, with the greatest risk concentrated within the first 7 to 14 days postoperatively [,]. The pathophysiology of postoperative hypercoagulability in orthopedic trauma patients is multifactorial, encompassing all three components of Virchow’s triad: endothelial injury caused by the surgical procedure itself, venous stasis secondary to immobilization and tourniquet use, and a systemic prothrombotic state driven by the activation of the coagulation cascade []. This hypercoagulable state begins immediately after tissue injury. Tissue factor release, platelet activation, thrombin generation, and fibrin deposition occur early and persist throughout the perioperative period [,]. Despite decades of research, the accurate and timely identification of patients at highest thrombotic risk remains a clinical challenge. Conventional coagulation tests—including prothrombin time (PT), activated partial thromboplastin time (aPTT), and international normalized ratio (INR)—reflect only isolated components of the coagulation cascade under static, plasma-based conditions and have demonstrated limited sensitivity in detecting the complex hemostatic alterations that characterize postoperative hypercoagulability []. These assays fail to account for the contributions of platelets, factor XIII, and the fibrinolytic system, thereby providing an incomplete picture of the patient’s true coagulation status [].