N5315 Advanced Pathophysiology Hematologic System Core Concepts and Objectives with Advanced Organizers

N5315 Advanced Pathophysiology Hematologic System Core Concepts and Objectives with Advanced Organizers Hemostasis PLATELET PLUG FORMATION Platelet Structure Function Peripheral zone -Outer most portion of cell -Cell membrane -Made of phospholipids. -Open cannicular system provides channels for substances produced by platelets to be produces and releases. -Phospholipid membrane provides a site for coag proteins and adhesive proteins to bind. Also produces thromboxane A2 via arachidonic path. -Contains platelet receptors which cause platelet adhesion and aggregation. Sol-gel zone -Middle layer -Structural support of the cell. Organelle Zone -Contains the organelles. The mitochondria, the dense tubular system (stores calcium & contains enzymes for prostaglandin synthesis), dense granules (contains ATP, ADP, serotonin, calcium, vWF, fibronectin, vitronectin, & thrombospondin) & alpha granules (contains platelet derived growth factor, platelet factor 4, Factor V, Kininogen, Factor XI, plasminogen activator inhibitor-1) are all located here. Four Phases of Platelet Plug Formation Function Activation -1st step of platelet plug. -Platelets normally flow freely, but injury to endothelium exposes clotting factors. -Collagen is released after injury, making platelets charged. (activated) -Platelets then undergo shape change=increasing ability to adhere to injury site. Adherence Adherence -Platelets attach to injured endothelium. -Adhesion begins with vWF. -vWf adheres with collagen and clotting factors making a connective binding and anchoring the platelets in place. Aggregation -Platelets binding together. -After platelet is activated, they link with fibrinogen and bind platelets together. Secretion -Platelet granules release their contents. a. ADP=enhances adhesion, activates platelets, & recruits platelets b. Serotonin= recruits platelets. c. Fibronectin and thrombospondin=stabilize platelets that are adhered to the site of injury. d. Thromboxane A2= product of the arachidonic acid pathway but is stored inside the platelet too. It causes vasoconstriction and enhances platelet aggregation. e. Growth factors= promote tissue repair but play role in the development of atherosclerosis. The platelet plug is stabilized by fibrin and XIIIa which are the end products of the coagulation cascade.  Extrinsic Pathway o Primary pathway of coagulation. o Activated when tissue factor is exposed at injury site. o Tissue factor binds with clotting factors o Fibrin is placed over platelet plug o Factor XIIIa stabilizes fibrin.  Intrinsic Pathway o Not entirely understood bc factor XII (Hageman factor) doesn’t cause bleeding. o Main function is to enhance extrinsic pathway. o Pathway is activated when blood is exposed to negative changes on ADP and ATP, which activates factor XII(Hageman). o XII binds with other clotting factors, forming the prothrombinase complex in common pathway