Pathophysiology of Bleeding and Clotting in the Cardiac Surgery Patient From Vascular Endothelium to Circulatory Assist Device Surface

Clinicians are faced with the challenge of navigating the precarious balance between bleeding and clotting. Bleeding disorders or failure to obtain adequate hemostasis during surgery may lead to severe hemorrhage. However, if thrombotic complications occur (eg, thromboembolic stroke), they may be far more difficult to treat. To achieve a stable equilibrium between bleeding and clotting, the treating physician should have a fundamental understanding of coagulation biology. In this article, we review the physiological role of the vascular endothelium in maintaining an antithrombogenic environment at baseline and a prothrombotic state after injury. Commonly used hemostatic and anticoagulant drugs and their mechanism of action are examined in this context. This is followed by a review of the most common inherited and acquired bleeding and clotting disorders, as well as the mechanism by which they lead to defects in coagulation biology. The approach to a bleeding patient is then discussed, including the interpretation of the most frequently used coagulation tests. Finally, we analyze mechanical assist device therapy as an extreme case of an acquired bleeding and clotting diathesis. The concept of blood coagulation dates back to the 1960s, when Davie, Ratnoff, and Macfarlane published articles in Nature and Science outlining the fundamental principle of a cascade of proenzymes activated through proteolytic cleavage that in turn activate “downstream” enzymes.1,2 Schematically, the coagulation system is divided into the extrinsic and intrinsic pathways (Figure 1 and Movie I in the online-only Data Supplement). The extrinsic pathway is triggered in response to tissue trauma and is initiated with exposure of tissue factor. The role of the intrinsic pathway is less clear in vivo but becomes important when the blood is activated via contact with artificial surfaces, such as a cardiopulmonary bypass circuit or a mechanical circulatory assist device (MCAD).3 Figure 1. Coagulation cascade. The extrinsic …