Disorders of platelet function.
Platelets provide for primary hemostasis by forming a hemostatic plug at sites of vascular damage. They also provide a surface for the assembly of the coagulation protein complexes that generate thrombin, serve as a nidus for fibrin clots, and secrete factors involved in wound repair. Normal platelet function can be divided into four phases: adhesion, aggregation, secretion, and expression of procoagulant activity. Platelet adhesion initiates plug formation as platelets adhere to the connective tissue at the edges of a wound within seconds after vascular damage. When damage occurs in regions of slow blood flow, platelets adhere to subendothelial collagen, fibronectin, and laminin. However, when damage occurs in regions of rapid flow, platelet adhesion requires the presence of subendothelial von Willebrand factor (vWf) and a specific platelet receptor, the glycoprotein Ib/IX (GPIb/IX) complex. Following initial adhesion, platelets aggregate to complete the formation of a hemostatic plug. Platelet aggregation requires active platelet metabolism, platelet stimulation by agonists such as ADP, thrombin, collagen, or epinephrine; the presence of calcium or magnesium ions and specific plasma proteins such as fibrinogen or vWf; and a platelet receptor, the glycoprotein IIb/IIIa (GPIIb/IIIa) complex. Thus, platelet stimulation results in the generation of intracellular second messengers that transmit the stimulus back to the platelet surface, exposing protein binding sites on GPIIb/IIIa. Fibrinogen (or vWf) then binds to GPIIb/IIIa and crosslinks adjacent platelets to produce platelet aggregates. Platelet stimulation also results in platelet secretion and the elaboration of platelet procoagulant activity. During secretion, substances are released to propagate the aggregation response and to promote wound healing; the expression of procoagulant activity localizes thrombin generation to the site of vascular damage. Disorders of platelet function can be divided into those of congenital and those of acquired origin. Although congenital disorders are uncommon, acquired disorders are encountered frequently in clinical practice. Congenital absence of GPIb/IX and GPIIb/IIIa results in the Bernard-Soulier syndrome (BSS) and Glanzmann thrombasthenia (GT), respectively. Each is an autosomal recessive bleeding disorder in which absence of a protein complex renders the affected platelets incapable of undergoing either vWf-mediated adhesion (BSS) or fibrinogen-mediated aggregation (GT).(ABSTRACT TRUNCATED AT 400 WORDS)
Bennett
J S
JS
Hematology/Oncology Division, University of Pennsylvania School of Medicine, Philadelphia.
Kolodziej
M A
MA
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000933:Antifibrinolytic Agents / Q000627:therapeutic use; D001777:Blood Coagulation / Q000502:physiology; D016913:Blood Component Transfusion; D001791:Blood Platelet Disorders / Q000145:classification / Q000209:etiology / Q000628:therapy; D001792:Blood Platelets / Q000378:metabolism / Q000502:physiology*; D003018:Clot Retraction; D003894:Deamino Arginine Vasopressin / Q000627:therapeutic use; D064420:Drug-Related Side Effects and Adverse Reactions; D004966:Estrogens, Conjugated (USP) / Q000627:therapeutic use; D006801:Humans; D015539:Platelet Activation; D010973:Platelet Adhesiveness; D010974:Platelet Aggregation; D015398:Signal Transduction
D000305:Adrenal Cortex Hormones; D000933:Antifibrinolytic Agents; D004966:Estrogens, Conjugated (USP); D003894:Deamino Arginine Vasopressin