Platelet dysfunction in the perioperative and critical care setting

Kwok M. Ho, Yusrah Harahsheh


Achieving haemostasis and, simultaneously, preventing venous thromboembolism (VTE) in the perioperative and critical care setting is challenging. Although the traditional coagulation parameters, including international normalised ratio (INR), activated partial thromboplastin time (aPTT) and platelet count, are important, evidence suggests that far more subtle aspects of platelet dysfunction may occur without antiplatelet therapy, and play a pivotal role both in critical bleeding and the pathogenesis of VTE. With advances in our ability to measure platelet activity and function beyond platelet count alone, we are making substantial progress in our understanding of how and when platelets interact and cross-talk with coagulation factors to achieve haemostasis and, conversely, contribute to the development of VTE after major surgery or trauma. With the ability to quantify the ability of platelets to aggregate, it is clear that platelet function tests have the potential to assist prediction of bleeding after cardiac surgery, especially for those who are treated with P2Y12-blockers. In addition, unregulated platelet activation or, conversely, platelet dysfunction in the absence of antiplatelet therapy, is increasingly being recognised as one of the key missing elements in the pathogenesis of VTE or critical bleeding, respectively. Our current understanding of the coagulation system—in particular the significance of platelet dysfunction and activation—may not be adaptive to benefit survival in all patients, especially after traumatic brain injury (TBI). Indeed, cardiolipin release from damaged neuronal mitochondria into the systemic circulation may explain why coagulopathy after TBI is associated with increased VTE instead of bleeding. Similarly, in patients with acquired coagulopathy due to liver disease, sepsis or trauma, excessive platelet activation has been observed explaining why these patients are not immune to developing VTE and, hence, VTE prophylaxis is still needed. While many drugs can inhibit platelet function through one of the three major platelet activation pathways—cyclooxygenase/thromboxane A2, P2Y12-ADP and thrombin—currently we do not have many interventions that can improve platelet function. Recent evidence suggested that an antioxidant polyphenol, resveratrol, may improve platelet function by reducing apoptosis and improving platelet mitochondrial function. We are now entering the exciting stage of precision-medicine in the area of coagulation in perioperative and critical care. Ultimately, we would be able use information beyond abnormal platelet count, INR and aPTT to guide platelet transfusion including withholding unnecessary platelet transfusion, and also avoid omission of VTE prophylaxis in the critically ill.