Clinical evaluation of a bleeding patient (Proceedings)


Clinical evaluation of a bleeding patient (Proceedings)

Apr 01, 2009

Abnormal bleeding or bruising is frequently encountered in veterinary clinical practice. Accurate diagnosis and treatment of the bleeding patient requires a basic understanding of the pathophysiology of hemostasis. A working knowledge of the hemostatic mechanism along with a complete medical history, thorough physical examination, and specific laboratory tests are integral steps in the diagnostic process. The most appropriate treatment options can only be identified after the cause of bleeding has been determined.


Hemostasis, the body's balancing mechanism of arresting hemorrhage while simultaneously maintaining blood flow within the vascular compartment, occurs through a complex series of events involving the vessels, platelets, plasma coagulation factors and the fibrinolytic system. The role that each component plays in hemostasis is dependent on the size of the vessel and the amount of damage that has occurred. Bleeding in smaller vessels may be controlled by a simple response involving the vasculature and platelets (e.g., normal wear and tear on capillaries), whereas incorporation of the plasma coagulation factors are necessary for hemorrhage control involving larger damaged vessels.

The first response to blood vessel injury is vasoconstriction, which allows for diversion of blood flow around the injured area. Once the endothelial lining of the vessel is disrupted, the subendothelial connective tissue (i.e., collagen fibers) is exposed. Circulating platelets pool to the area of injury and, with the help of certain adhesive proteins (i.e., collagen, fibrinogen, fibronectin, von Willebrand factor), adhere to the endothelial lining to arrest the initial episode of bleeding. This process is known as platelet adhesion. Once the platelets adhere to the subendothelium, they change shape and secrete certain biochemical substances that enhance platelet layering in the injured area. The platelets form a complete but unstable plug. This portion of the hemostatic process involving the vasculature and platelets is referred to as primary hemostasis and is usually adequate to stop bleeding in smaller vessels.

With greater damage to larger vessels, coagulation factors are needed to form a stable fibrin clot, a process known as secondary hemostasis. Blood coagulation involves a complex process by which the multiple coagulation factors contained in blood interact in three major pathways: the intrinsic, extrinsic and common pathways.

Plasma coagulation factors (denoted by Roman numerals) are produced in the liver, many with the help of vitamin K. They circulate in the blood in the inactive form and become activated only when exposed to certain substances. Initiation of the extrinsic and intrinsic clotting pathways leads to subsequent activation of all factors in a cascade-like effect.

Tissue factor (thromboplastin) is released from the injured vessel wall and initiates the extrinsic clotting pathway. This is an extravascular process in that tissue thromboplastin is not normally found in blood and must gain entry to the vascular system. Clotting via the intrinsic pathway begins when blood comes into contact with a foreign substance or surface (i.e., damaged endothelium). Activated platelets release a phospholipid allowing coagulation factors in this pathway to activate one another. In the intrinsic pathway, all factors necessary for clot formation are within the intravascular compartment. Both the extrinsic and intrinsic pathways merge into the common pathway, where the end result is the creation of fibrin, a threadlike protein. The fibrin threads form an insoluble meshwork over the site of the platelet plug, consolidating and stabilizing the clot.

**For simplicity of presentation, the pathways have been reviewed as divided processes. The reader must realize that classic cascade presentation of fibrin formation has many underlying complexities and interrelationships that go beyond the scope of this paper.

The fourth and final step in the hemostatic process is fibrinolysis. Once the vessel is healed, fibrinolytic enzymes digest the clot that has been formed, restoring normal blood flow. Clot lysis produces small pieces of fibrin, referred to as fibrin split products (FSP) (or fibrin degradation products FDP), which are cleared from circulation by the liver. Small levels of FSPs always appear in the circulation as a result of bleeding and clotting secondary to normal wear-and-tear on vessels. FSP levels increase during episodes of excessive bleeding with diffuse coagulation (i.e., disseminated intravascular coagulation {DIC}) and in patients with compromised liver function. Following clot digestion, vessel wall endothelium is reestablished and returned to its original state.

In summary, bleeding disorders can be categorized into three groups: disorders of platelet function or number, disorders of clotting factors, and a combination of both.