Brain regulation of thrombosis and hemostasis: from theory to practice.

T hrombosis and hemostasis impact stroke neurology and cerebrovascular disease. Decision making for stroke prevention and stroke treatment almost invariably involves phar-macotherapies that involve coagulation, with drugs ranging from aspirin to anticoagulants, both new and old. Nevertheless, the focus on pharmacotherapy modulation of coagulation processes tends to overlook some basic pathophysiological realities: the organ affected by stroke has its own unique system for regulation of thrombosis and hemostasis. The purpose of this article is to review the brain's intrinsic capacity for thrombosis and hemostasis regulation. At first glance, it may seem that this is esoteric subject matter. Indeed, until recently, it seemed that this material was largely of theoretical interest. It is now evident that thrombosis, hemostasis, and the brain have enormous practical significance for the field of stroke neurology. Intrinsic regulation of thrombosis and hemostasis can no longer be ignored if one is to intervene pharmacologically in ways that impact coagulation. Manipulation of sys-temic coagulation factors will necessarily have consequences implicating intrinsic brain regulatory mechanisms. This article will review thrombosis and hemostasis from an organ-specific perspective and one organ in particular: the brain. The article will address how brain regulation of thrombosis and hemostasis manifests itself in the context of organ-specific regulation. The phenomenon of cerebral microbleeds will then be discussed as a pivotal and perhaps paradigmatic example of the importance of this issue. The terms thrombosis, hemostasis, and coagulation are sometimes used interchangeably, but more precisely refer to different processes. Hemostasis defines the avoidance or arrest of bleeding by maintaining blood within a vessel. Thrombosis is the formation of clot within a blood vessel, resulting in obstruction of flow, whereas coagulation refers to a liquid transformed into a coherent solid or semisolid mass. 1 Coagulation is primarily regulated by circulating soluble factors, circulating cells, and vessel wall constituents, combined with vascular integrity and blood flow. Circulating cells are considered the components of primary hemostasis, whereas circulating coagulation factors constitute secondary hemostasis. 1 The 4-component model of coagulation (hepatic factors, bone marrow–derived hematopoietic cells, vascu-lar tree, and endothelium) represents a useful conceptual approach to this complex system, in which primary hemosta-sis consists of the relevant bone marrow–derived cells (plate-lets and monocytes) while the liver provides the coagulation factors of secondary hemostasis. 1 Another model incorporates the classical Virchow triad, consisting of alterations of blood flow, blood wall, and blood constituents. This model is typically used to explain predilec-tion for …