Primary Hemostasis PDF

4 PRIMARY HEMOSTASIS PRIMARY HEMOSTASIS Primary hemostasis is initiated by the exposure of platelets to the subendothelial connective tissue components blood vessels (Collagen, microfilaments, basement membranes). 1. VASCULAR RESPONSE Vascular injury to a large or medium-size artery or vein requires...

4 PRIMARY HEMOSTASIS PRIMARY HEMOSTASIS Primary hemostasis is initiated by the exposure of platelets to the subendothelial connective tissue components blood vessels (Collagen, microfilaments, basement membranes). 1. VASCULAR RESPONSE Vascular injury to a large or medium-size artery or vein requires rapid surgical intervention to prevent exsanguination. When a smaller vessel, such as an arteriole, venule, or capillary, is injured, contraction occurs to control bleeding. This contraction of the blood vessel wall is called vasoconstriction. Vascular integrity or the resistance to vessel disruption requires three essential factors. These factors are: CIRCULATING PLATELETS Form plugs in blood vessel injuries to prevent bleeding. Platelets also release chemicals that help to attract other cells involved in wound healing to the site of injury. Adrenocorticosteroids Possess anti-inflammatory properties that can reduce vascular inflammation. hormones produced by the adrenal glands that can help to reduce inflammation. ASCORBIC ACID Necessary for collagen synthesis Deficiency can lead to fragile blood vessels and increased risk of bruising. Endothelial Prothrombotic-Antithrombotic Balance Prothrombic Platelet activating factor Tissue factor Vwf Plasminogen activator Inhibitor-1 Other coagulation factors (e.g factor V) Antithrombic Prostacyclin Thrombomodulin Tissue plasminogen activator Urokinase Heparin like molecules Endothelial Vasoconstrictor-Vasodilator Balance Constrictor Endothelin-1 Angiotensin-2 Prostaglandins Dilator Prostacyclin Nitric oxide 2. platelet RESPONSE Platelets have an average diameter of 2 to 4 um, with younger platelets being larger than older ones. In contrast to megakaryocytes platelets have no nucleus. The cytoplasm is light blue, with evenly dispersed, fine red-purple granules. An inactive or unstimulated platelet circulates as a thin, smoothsurfaced disc. This discoid shape is maintained by the microtubular cytoskeleton beneath the cytoplasmic membrane. Platelets are extremely sensitive cells and may respond to minimal stimulation by forming pseudopods that spontaneously retract. Stronger stimulation causes platelets to become sticky without losing their discoid shape; however, changes in shape to an irregular sphere with spiny pseudopods will occur with additional stimulation. This alteration in cellular shape is triggered by an increase in the level of cytoplasmic calcium. PLATELET ACTIVATION AGONISTS a. ADP b. thromboxane A2 c. platelet-activating factor d. collagen e. thrombin 2.1 Platelet Adhesion When vascular injury occurs, platelet come in contact with subendothelium (collagen, fibronectin). vWf binds to glycoprotein Ib/IIb or the GP Ib/IX/V complex on platelet surface If vascular injury exposes the endothelial surface and underlying collagen, platelets adhere to the subendothelial collagen fibers, spread pseudopods along the surface, and clump together (aggregate). Platelet adhesion to subendothelial connective tissues, especially collagen, occurs within 1 to 2 minutes after a break in the endothelium. 2.2 Platelet Activation Morphological and functional change in plateLETS. Cyclooxygenase (from the platelets) metabolizes arachidonic acid to form prostaglandin enderoperoxides, which are converted to thromboxane A2 (a vasoconstrictor and a platelet stimulator, causing platelet secretion and aggregation) Aspirin inhibits cyclooxygenase pathway (remission after 7 to 10days) 2.3 Platelet secretion Following activation, platelet undergoes a shape change most probably caused by contraction of microtubules From a disk shape to spherical shape with the extrusion of numerous pseudopods Platelet granules move to the center of the platelets and fuse with the open canalicular system connected to the outside of the platelet; in this way the content of the granules are extruded to the outside 2.4 Platelet aggregation Simultaneously with platelet release, platelet stimulating agents (collagen, ADP, epinephrine, thrombin) bind to the platelets, causing then to adherence to one another Platelet stimulating agents such as collagen, ADP, epinephrine, thrombin binds to platelets, causing them to adhere to one another. Fibrinogen binds to GP IIb/ IIIa receptors on adjacent platelets and joins them together in the presence of ionized calcium Fibrinogen is necessary as cofactor for platelet aggregation Bridges formed by fibrinogen in the presence of calcium produce a sticky surface on platelets. This results in aggregation. If these aggregates are reinforced by fibrin, they are referred to as a thrombus 3. Platelet Plug Consolidation and Stabilization Fibrinogen, under the influence of small amounts of thrombin, provides the basis for this consolidation and stabilization. This process involves the precipitation of polymerized fibrin around each platelet. The result is a fibrin clot that produces an irreversible platelet plug. PROMOTES COAGULATION SUBSTANCE SOURCE FUNCTION HMWK activation of intrinsic coagulation Alpha granules Contact pathway Fibrinogen Alpha granules Converted to fibrin clot formation Factor V Alpha granules Cofactor in fibrin clot formation FactorVIII:Vwf platelet adhesion to subendothelial to Alpha granules Assist provide coagulation surface PROMOTES AGGREGATION SUBSTANCE SOURCE FUNCTION ADP Dense granules Promote platelet aggregation Calcium Dense granules Promote platelet aggregation Platelet factor 4 Alpha granules Promote platelet aggregation PROMOTES vasoconstriction SUBSTANCE SOURCE FUNCTION Serotonin Dense granules Promotes vasoconstriction at injury site Thromboxane A2 Membrane Promotes vasoconstriction at injury site phospholipids Promote vascular repair SUBSTANCE SOURCE FUNCTION Platelet derived growth factor smooth muscle growth for vessel Alpha granules Promotes repair Beta thromboglobulin for fibroblasts to help in Alpha granules Chemotactic vessel repair Other systems affected SUBSTANCE SOURCE FUNCTION Plasminogen Precursor to plasmin, which induces clot Alpha granules lysis Alpha 2 antiplasmin Alpha granules Plasmin inhibitor; inhibits clot lysis C1 esterase inhibitor Alpha granules Complement system inhibitor