Bleeding Disorders

The body possesses innate mechanisms to control bleeding in the setting of an injury. An understanding of these basic physiologic processes is critical to aid in the identification and diagnosis of bleeding disorders. The hemostatic system is responsible for maintaining blood in a fluid state, free of the aggregation of platelets and thrombus formation with the help of prostacyclin, antithrombin III and nitric oxide within the endothelial cells. These naturally occurring substances found in the blood assist in the prevention of clots by causing conversion of plasminogen to plasmin to promote fibrinolysis. Damage or injury to the endothelium will initiate a cascade of events in an attempt to control bleeding. Disruption of the endothelium will first cause local vasoconstriction to occur, limiting blood flow to the area. Primary hemostasis initiates by platelets with the release of von Willebrand factor (vWF), a large plasma glycoprotein made and stored in endothelial cells and megakaryocytes. Platelets and vWF will combine to form a plug at the site of injury. Circulating vWF continues to bind with collagen and Factor VIII as well as other endothelial substances, allowing the platelet plug to adhere to the area of injury. Through activation of the clotting cascade (see image) and secondary hemostasis, this initial platelet plug will get reinforced to a sturdy fibrin clot. The clotting cascade operates through a dual process system in which the various clotting factors become activated with the result being the formation of a fibrin strand or clot at the site of tissue injury. A deficiency of any of the essential clotting factors will result in difficulty forming a fibrin clot, and excessive bleeding can occur.

Bleeding disorders fall into two main categories: inherited and acquired. Inherited bleeding disorders have a genetic predisposition and involve a deficiency of coagulation factors. Acquired bleeding disorders can be caused by conditions that an individual may develop at any point during their lifetime. These can be broader in range and dependent on comorbid conditions. The focus of this discussion will be on congenital coagulopathies; acquired bleeding disorders will be considered to be outside the scope of the information presented here.