Human disease info

Inherited defects in platelet function are rare and produce mucosal bleeding when severe. Ac­quired defects in platelet function are common and are chiefly associated with drug ingestion— particularly of aspirin—or with underlying he­matologic disease. They become clinically im­portant if accompanied by another hemostatic de­fect, such as thrombocytopenia, or during therapy with anticoagulants. Acquired platelet function defects may also cause excessive bleeding at sur­gery. Evaluation of platelet disorders requires spe­cialized testing .

Congenital platelet disorders include throm­basthenia (Glanzmann’s syndrome), character­ized by a prolonged bleeding time, absent platelet aggregation despite normal platelet adhesion to collagen, and episodes of mucosal bleeding. The disorder is transmitted by an autosomal recessive gene. Thrombasthenic platelets lack two surface glycoproteins (lib and Ilia) necessary for fibrino­gen binding to the platelet membrane and for platelet aggregation. Bleeding may be life-threat­ening. The only therapy is transfusion of normal platelets. Platelet-release defects resulting in im­paired platelet aggregation comprise several syn

dromes. First, a mild bleeding tendency results from an “aspirin-like” defect in which all platelet structures are normal, but normal activation does not take place when platelets are exposed to the usual agonists. The causes of this syndrome in­clude defective phospholipase activation or a de­ficiency in enzymes of the prostaglandin path­way, such as cyclooxygenase or thromboxane synthase. Several types of storage-pool deficiency present with impaired platelet-release reactions, associated with poor platelet aggregation, a long bleeding time, and mucosal bleeding. The storage pool deficiencies are varied: they comprise de­fects in platelet granule storage of ADP or sero­tonin or abnormalities in platelet granule struc­ture. In the Hermansky-Pudlak syndrome, platelet granule abnormalities are associated with albinism. An acquired storage pool defect occurs after exposure of blood to extracorporeal circu­lation and, rarely, in myeloproliferative disease. Since ADP release is necessary for normal platelet function, defective storage or release results in a hemorrhagic tendency. Bleeding episodes in af­fected patients are usually limited to trauma, sur­gery, or childbirth. Aspirin and nonsteroidal as­pirin-like drugs should be avoided. As in thrombasthenia, platelet transfusion provides the only therapy.

Platelet adhesion is abnormal in two inherited bleeding disorders: von Willebrand’s disease and the Bernard-Soulier syndrome. Von Willebrand’s disease is a common bleeding disorder that affects both sexes and is transmitted as an autosomal re­cessive trait. In this condition, platelets are nor­mal in structure and number but fail to adhere to the vascular subendothelium because of the- lack of a plasma factor essential for platelet interaction with collagen in the vessel wall. The von Wille­brand’s factor (VWF), which is synthesized in vas­cular endothelial cells and in megakaryocytes, normally circulates in a macromolecular complex with coagulation Factor VHI. In addition to de­creased, absent, or abnormal VWF, patients with von Willebrand’s disease also have decreased co­agulation Factor VIII. In von Willebrand’s disease, laboratory findings include a prolonged bleeding time, poor platelet adhesion, and normal platelet aggregation, but absent agglutination of platelets by the antibiotic ristocetin, which requires VWF. The clinical manifestations include mucosal bleeding, menorrhagia, and bruising. Both labo­ratory and clinical abnormalities are corrected by administration of VWF. Further discussion of von Willebrand’s disease follows the discussion of hemophilia A.

In Bernard-SouJier syndrome, a very rare au­tosomal recessive disease, giant platelets are ob­served on the blood smear, the bleeding time is prolonged, and mucosal hemorrhage is common. A platelet membrane glycoprotein (lb) that me­diates VWF binding is absent. Plasma VWF is nor­mal, but VWF cannot correct defective platelet adhesion in the absence of the platelet receptor. Treatment is limited to platelet transfusion.

The gray-platelet syndrome consists of a lack of platelet alpha granules containing VWF, fibro-nectin and thrombospondin, the proteins neces­sary for normal platelet adhesion and aggregation. Their deficiency leads to a mild bleeding ten­dency, correctable by platelet transfusion.
Thrombocytopathy or impaired expression of platelet procoagulant activity, i.e., the accelera­tion of thrombin formation by the surface of ac­tivated platelets, produces a mild bleeding ten­dency mainly following trauma or surgery.

Tags: agonists, autosomal recessive gene, cyclooxygenase, drug ingestion, hemostatic, hermansky pudlak syndrome, life threat, path way, phospholipase, platelet adhesion, platelet aggregation, platelet disorders, prostaglandin, sero, storage pool, surface glycoproteins, thrombocytopenia, thromboxane, tonin

• PHYSIOLOGY OF THE SYSTEMIC CIRCULATION
• CARDIAC DEVELOPMENT
• CARDIOVASCULAR PHYSIOLOGY DURING PREGNANCY - ELECTROPHYSIOLOGY
• ACQUIRED DISORDERS OF PLATELET FUNCTIOII
• GROSS ANATOMY
• MICROSCOPIC ANATOMY
• MYOCARDIAL METABOLISM
• CARDIOVASCULAR RESPONSE TO EXERCISE
• QUALITATIVE PLATELET DISORDERS
• PHYSIOLOGY OF THE PULMONARY CIRCULATION
• PHYSIOLOGY OF THE CORONARY CIRCULATION
• CIRCULATORY PHYSIOLOGY
• ELECTRICAL CONDUCTION SYSTEM