Inherited platelet disorders constitute a large group of diseases involving a wide range of genetic defects that can lead to bleeding symptoms of varying severity.
Platelets are blood cells that help repair injured blood vessels. Also known as thromobocytes, platelets stop the loss of blood by plugging holes in blood vessels, the first step in the formation of a clot. Adenosine diphosphate (ADP) and thrombin are then released from the activated platelets and thromboxane A2 is generated, causing platelet aggregation. The platelet release reaction follows with the secretion of fibrinogen, von Willebrand factor, factor V, platelet factor 4, and B-thromboglobulin from the alpha granules and serotonin, calcium ions, ADP, and adenosine triphosphate (ATP) from the dense bodies. This forms the platelet plug. Platelet coagulant activity is then produced, primarily through platelet factor 3, which ultimately, with the plasma clotting factors, leads to the formation of the fibrin clot, the final step in the coagulation sequence. Like most blood cells, they form in the bone marrow and then migrate into the blood.
Role of Platelets Blood Coagulation
The critical role played by platelets in stopping bleeding and formation of clot is related to their function as cells that secrete effector molecules at the side of vascular injury. Platelets contain at least 3 types of intracellular granules, in which these mediators are stored and concentrated, known as alpha, dense and lysosomal granules.
While alpha granules contain mainly polypeptides, as fibrinogen, von Willebrandt factor, growth factors and protease
inhibitors, dense granules contain small molecules specifically ADP, ATP, serotonin, and calcium.
Humans with defective dense granule exocytosis suffer from delta storage pool disease associated with a moderate bleeding tendency. The most severe delta storage pool disease is observed in Hermansky-Pudlak syndrome (HPS), a rare autosomal recessive
disorder in which oculocutaneous albinism, bleeding, and lysosomal ceroid storage result from defects of melanosomes, platelet-dense granules, and lysosomes.
The term Delta-storage pool deficiency (SPD) has been used to identify patients who show only a diminished number of Delta-granules. Delta-Granules contain calcium, serotonin, pyrophosphate, adenosine diphosphate, and adenosine triphosphate. Delta-storage pool disease, also called dense granule deficiency, causes a mild to moderate bleeding tendency after minor trauma, venipuncture, and surgery marked by prolonged bleeding time. Inheritance is autosomal dominant. Severe platelet disorders may require platelet transfusions.