Platelets and Hemostasis 2024 PDF

LESSON 4. HEMOSTASIS. Blood clotting. 1. PLATELETS 2. HEMOSTASIS 2.1. Vascular Spasm 2.2. Platelet Plug Formation 2.3. Blood Clotting 2.3.1. The Extrinsic Pathway 2.3.2. The Intrinsic Pathway 2.3.3. The Common Pathway 2.3....

LESSON 4. HEMOSTASIS. Blood clotting. 1. PLATELETS 2. HEMOSTASIS 2.1. Vascular Spasm 2.2. Platelet Plug Formation 2.3. Blood Clotting 2.3.1. The Extrinsic Pathway 2.3.2. The Intrinsic Pathway 2.3.3. The Common Pathway 2.3.4. Clot Retraction 2.3.5. Role of Vitamin K in Clotting 2.4. Hemostatic Control Mechanisms 1. PLATELETS red bone marrow Blood Hormone thrombopoietin 2  Platelets help stop blood loss from damaged blood vessels by forming a platelet plug. Their granules also contain chemicals that promote blood clotting. Platelets have a short life: 5-9 days. Aged and dead platelets are removed by fixed macrophages in the spleen and liver.  2. HEMOSTASIS Hemostasis = sequence of responses that stops bleeding. When blood vessels are damaged the hemostatic response must be: – quick, – localized to the region of damage, – carefully controlled Three mechanisms reduce blood loss: (1) vascular spasm (2) Platelet plug formation (3) blood clotting (coagulation) Ç 4 2.1. Vascular spam Vascular spasm = when arteries or arterioles are damaged, the circularly arranged smooth muscle in their walls contracts. This reduces blood loss for several minutes to several hours, during which time the other hemostatic mechanisms go into operation. The spasm is caused by: – damage to the smooth muscle – substances released from activated platelets – reflexes initiated by pain receptors 5 1. Platelet adhesion: platelets contact and stick to damaged blood vessel (collagen fibers of connective tissue underlying damaged endothelial cells). 2. Platelet release reaction: platelets activated: They extend projections that enable them to contact with one another They begin to liberate contents of their vesicles: – ADP and thromboxane A2: activate nearby platelets. – Serotonin and thromboxane A2: vasoconstrictors (decreases blood flow) 3. Platelet aggregation: The release of ADP makes other platelets sticky and causes them to adhere to the originally activated platelets. Form a mass called a platelet plug. 6  A platelet plug is very effective in preventing blood loss in a small vessel. Although initially the platelet plug is loose, it becomes quite tight when reinforced by fibrin threads formed during clotting. Normally, blood remains in its liquid form within its vessels. If it is drawn from the body, it thickens and forms a gel. The gel separates from the liquid. The straw-colored liquid, called serum, is simply blood plasma minus the clotting proteins. The gel is called a clot. It consists of insoluble protein fibers called fibrin in which the formed elements of blood are trapped.  2.3. Blood Clotting Clotting or coagulation = series of chemical reactions that culminates in formation of fibrin threads. Clotting involves several substances known as clotting (coagulation) factors. These factors include calcium ions (Ca2+), several inactive enzymes that are synthesized by liver cells, and molecules associated with platelets or released by damaged tissues. Most clotting factors are identified by Roman numerals, indicate order of their discovery. 8  Clotting is a cascade of enzymatic reactions in which each clotting factor activates many molecules of the next one. Finally, a large quantity insoluble protein, fibrin, is formed. Clotting can be divided into three stages: 1. 2 pathways, the extrinsic pathway and the intrinsic pathway, lead to the formation of prothrombinase. Once prothrombinase is formed, the steps involved in the next two stages of clotting are referred to as the common pathway. 2. Prothrombinase converts prothrombin (formed by the liver) into thrombin. 3. Thrombin converts soluble fibrinogen (formed by the liver) into insoluble fibrin. Fibrin forms the threads of the clot  2.3.1. The Extrinsic Pathway Few steps. Occurs rapidly. A tissue protein called tissue factor (TF), also known as thromboplastin, leaks into the blood from cells outside blood vessels and initiates the formation of prothrombinase. In the presence of Ca2+, TF begins a sequence of reactions that u activates clotting factor X. Once factor X is activated, it combines with factor V in the presence of Ca2+ to form prothrombinase,.  2.3.2. The Intrinsic Pathway More complex, more slowly. Its activators are either in direct contact with blood or contained within the blood. Contact with collagen fibers (or with the glass sides of a blood collection tube) activates clotting factor XII, which begins a sequence of reactions that eventually activates clotting factor X. Platelet phospholipids and Ca2+ can also participate in the activation of factor X. Once factor X is activated, it combines with factor V to form the active enzyme prothrombinase. 2.3.3. The Common Pathway Prothrombinase and Ca2+ catalyze the conversion of prothrombin to thrombin. Thrombin, in the presence of Ca2+, converts fibrinogen, which is soluble, to fibrin, which is insoluble. 12 2.3.4. Clot Retraction Clot retraction is the consolidation or tightening of the fibrin clot. Permanent repair of the blood vessel can then take place. 2.3.5. Role of Vitamin K in Clotting Normal clotting depends on adequate levels of vitamin K in the body. It is required for the synthesis of four clotting factors: II, VII, IX, X. Normally produced by bacteria that inhabit the large intestine, vitamin K is a fat-soluble vitamin. 13 2.4. Hemostatic Control Mechanisms The fibrinolytic system dissolves small, inappropriate clots; it also dissolves clots at a site of damage once the damage is repaired. Dissolution of a clot is called fibrinolysis. When a clot is formed, an inactive plasma enzyme called plasminogen is incorporated into the clot. Both body tissues and blood contain substances that can activate plasminogen to plasmin (fibrinolysin). Once plasmin is formed, it can dissolve the clot. Several other mechanisms also control blood clotting. Anticoagulants are present in blood: – antithrombin, which blocks the action of several factors; – heparin, combines with antithrombin and increases its effectiveness in blocking thrombin. – activated protein C (APC), inactivates the two major clotting factors not blocked by antithrombin and enhances activity of plasminogen activators. 14 15