PLATELET ADHESION AND ACTIVATION, PLATELET RELEASE REACTION: Following blood vessel injury, platelets adhere to the exposed subendothelial connective tissues. Subendothelial microfibrils bind the larger multi-members of
VWF which bind to platelet membrane 1b complex. Under the influence of shear stress platelets move along the surface of vessels until the platelet surface GpIa/IIa engages collagen and halts translocation.
Following adhesion, platelets become more spherical and extrude long pseudopods which enhance interaction between adjacent platelets.Platelet activation is then achieved by glycoprotein 11b/111a binding fibrinogen to produce platelet aggregation. The 11b-111a receptor complex also forms a secondary binding site with VFW further promoting adhesion.
VON WILLEBRAND FACTOR VWF
Von willebrand factor (VWF) is involved in platelet adhesion to the vessel wall and to other platelets (aggregation). It also carries factor V111. It is a large complex muti-mericmolecule (molecular weight (MW)0.8-20x106) made up of several subunit chains ranging from dimmers (MW 5x105) to mutimers (MW 20x106) linked by disulphide bonds.
Von Willebrand Factor is encoded by a gene o chromosome 12 and is synthesized by endothelial cells and megakaryocytes. It is stored in Weibel-palade bodies in endothelial cells and in specific platelet alpha granules. Release of VWF from the endothelial cells occurs under the influence of several hormones. Stress and exercise or infusion of either adrenalin or desmopressin (1-deamino-8-D- arginine vasopressin, DDAVP) produces considerable increase in the level of circulation VWF.
PLATELET RELEASE REACTION IN platelet adhesion
Collagen exposure or thrombin action results in the secretion of platelet granule contents which include ADP, serotonin, fibrinogen, lysosomal enzymes, B-thrombogiobulin and heparin neutralizing factor IX (platelet factor Iv). There is membrane release of diacylglycerol (which activates protein phosphorylation via protein kinase C) and inositol triphosphate (which causes release of intracellular calcium ions).
There is also arachidoate release from the cell membrane leading to the formation of a labile substance, thromboxane A2, which lower platelet cyclic adenosine monophosphate (cAMP) and initiates the release reaction. Thromboxane A2 not only potentiates platelet aggregation but also has powerful vasoconstrictive activity.
The release reaction is inhibited by substances which increase the level of platelet cAMP. One such substance is the prostaglandin prostacyclin which is synthesized by the vascular endothelial cells. It is a potent inhibitor of platelet aggregation and prevents their deposition on normal vascular endothelium.
Released ADP and thromboxane A2 cause additional platelets to aggregate at the site of vascular injury. ADP causes platelets to swell and encourages platelet membranes of adjacent platelets to adhere to each other. As they do so further release reactions occur liberating more ADP and thromboxane A2 causing secondary platelet aggregation. This positive feedback process results in the formation of a platelet mass large enough to plug the area of endothelial injury.
PLATELET COAGULANT ACTIVITY
After platelet aggregation and release the exposed membrane phospholipids (platelet factor 3) is available for two reactions in the coagulation cascade. Both phospholipids-mediated reactions are calcium-ion dependent. The first (tenase) involves factors IXa, VIIIa and X in the formation of factor Xa. The second (prothrombinase) results in the formation of thrombin from the interaction of factors Xa, Va and prothrombin (II). The phospholipids surface forms an ideal template for the crucial concentration and orientation of these proteins.
- Platelets: Flow Cytometry- Platelets can be evaluated for functional defects using flow cytometry. This test uses lasers to determine proteins that are present on the
platelets surface and how they
- Platelets: BRIEF HISTORY- From antiquity to the 1800s, salicylates from plants sources (white willow, Salix alba) provided a folk remedy for pain and fever. In the mid-1800s, salicylic acid was synthesized in Europe, followed shortly thereafter by the synthesis of acetyl-salicylic.