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Learning Objectives

  1. Learn the basic molecular events in clot formation and fibrinolysis.

  2. Understand the basic classification of disorders in hemostasis.

  3. Identify the appropriate laboratory tests for evaluation of the bleeding patient and the thrombotic patient.

  4. Learn the prominent clinical and laboratory features of the individual disorders of hemostasis.

The coagulopathies are grouped into disorders of bleeding and thrombosis. The hemorrhagic diseases are further subdivided into the 2 major categories of coagulation factor disorders and platelet disorders. To understand the diseases with abnormal coagulation that follow, a brief introduction to normal hemostasis precedes the discussions of the diseases.

Introduction to Hemostasis

Normal hemostasis is the controlled activation of coagulation factors and platelets leading to clot formation, with subsequent clot lysis, in a process that stops hemorrhage without excess clotting (thrombosis). Effective hemostasis is a rapid and localized response to an interruption in vascular integrity (vessel wall injury), such that clots are formed only when and where they are needed.

Clot Formation

Clot formation involves platelet activation and the subsequent generation of fibrin via the coagulation cascade. The 2 processes are discussed separately in the sections that follow.

Platelet Plug Formation

Platelet plug formation is initiated in vivo by exposure of platelets to vascular subendothelium when a vessel is injured. The platelets adhere to the subendothelium, spread out along the surface, and release substances that promote the aggregation of other platelets at that site. The platelets also accelerate fibrin clot formation by providing a reactive surface for several steps in the coagulation cascade.

Clot formation involves platelet activation and the subsequent generation of fibrin via the coagulation cascade.

Adhesion of platelets to the subendothelial surface is facilitated by a plasma protein, von Willebrand factor (vWF), especially in vessels with high shear forces (eg, the fast blood flow in arteries has a higher shear force than slow blood flow in veins). vWF binds to a specific receptor on the platelet surface. Deficiency of vWF results in poor adherence of platelets to subendothelium. The severity of bleeding in von Willebrand disease (vWD) varies widely among patients. Another related platelet adhesion defect occurs in patients whose platelets lack the receptor for vWF. This bleeding disorder, known as Bernard–Soulier disease, results from an inability of platelets to bind vWF.

Platelet activation occurs from interaction of platelet agonists, most of which are soluble, with specific receptors on the platelet membrane. Physiologically important agonists include adenosine diphosphate (ADP), thrombin, epinephrine, collagen, and thromboxane A2, which is derived from arachidonic acid. A sequence of membrane and cytoplasmic events is initiated by the agonist–receptor interaction, involving an increase in cytoplasmic calcium ion concentration and a platelet shape change from a disc to a spiny sphere. The change in cytoplasmic calcium concentration leads to contractile ...

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