Lecture 5 ZRo Hemostasis and Blood Coagulation Lecture Notes PDF

Hemostasis and Blood Coagulation Lecture 5 Ishraq Jasim [email protected]  Events in Hemostasis The term hemostasis means prevention of blood loss Whenever a vessel is cut or ruptured, hemostasis is achieved by several mechanisms...

Hemostasis and Blood Coagulation Lecture 5 Ishraq Jasim [email protected]  Events in Hemostasis The term hemostasis means prevention of blood loss Whenever a vessel is cut or ruptured, hemostasis is achieved by several mechanisms: (1) Vascular constriction (2) Formation of a platelet plug (3) Formation of a blood clot (4) Growth of fibrous tissue into the blood clot  1. Vascular Constriction The contraction results from: 1. Local myogenic spasm (vasoconstriction) 2. Local autacoid factors 3. Nervous reflexes (pain nerve). Platelets release a vasoconstrictor thromboxane A2 which is responsible on contraction of the small vessels. The more severely a vessel is traumatized, the greater of degree of vascular spasm.  Formation of the Platelet Plug (Primary Hemostasis) Very small cut is often sealed by a platelet plug rather than by a blood clot.  Physical and Chemical Characteristics of Platelets Platelets (thrombocytes) are minute discs 1-4 µm in diameter. Formed from megakaryocytes. The normal concentration: 150,000 - 450,000 / µl. It has a half-life in the blood: 8-12 days.  Platelets don’t have nuclei and they cannot reproduce. Importance of platelets cell membrane: it has 1. Coat of glycoproteins: causes adherence of platelets to injured endothelial cells. 2. Phospholipids: activate multiple stages in the blood-clotting process. Mechanism of the Platelet Plug Change their own characteristics after contact a damaged vascular surface (collagen fibers). They begin to swell; they assume irregular forms with numerous irradiating pseudopods protruding from their surfaces Force contraction of their contractile protein s release of granules that contain multiple active factors They become sticky adherance to collagen in the tissues and to von Willebrand factor that leaks into the traumatized tissue from the plasma. They secrete large quantities of ADP; and thromboxane A2 Importance of the Platelet Mechanism for Closing Vascular Holes The platelet-plugging mechanism is extremely important for closing minute ruptures in very small blood vessels A person who has low platelets count develops small hemorrhagic areas (petechiae or purpura), but this does not occur in the normal person. 3- Blood Coagulation The clot begins to develop in 15 - 20 seconds if the trauma to the vascular wall has been severe, and in 1 - 2 minutes if the trauma has been minor. Clotting time is about 3-6 min after rupture of a vessel, if the vessel opening is not too large. Clot retraction occurs after 20 min- 1hour, to further closes the vessel. Platelets also play an important role in this clot retraction. 4. Dissolution of the Blood Clot Once a blood clot has formed, it can follow one of two courses: 1) It can become invaded by fibroblasts, which subsequently form connective tissue all through the clot. 2) It can dissolve, when excess blood has leaked into the tissues and tissue clots have occurred where they are not needed, special substances within the clot itself usually become activated. These function as enzymes to dissolve the clot.  Mechanism of Blood Coagulation More than 50 important substances cause or affect blood coagulation have been found in the blood and in the tissue. Procoagulants: promote coagulation (activated after injury). Anticoagulants: inhibit coagulation (normally predominate). Coagulation depends on the balance between both. Clotting Factors in Blood and Their Synonyms Important difference between the extrinsic and intrinsic pathways Activation of Plasminogen to Form Plasmin: When a clot is formed, a large amount of plasminogen is trapped in the clot. The injured tissues and vascular endothelium very slowly release a powerful activator called tissue plasminogen activator (t-PA). Tissue plasminogen activator (t-PA) converts plasminogen to plasmin, which in turn removes the remaining unnecessary  Clot Retraction-Serum Contract the clot within a few min Expresses most of the fluid from the clot within 20-60 min Release pro-coagulant (fibrin-stabilizing factor) to increase cross-linking bonds between adjacent fibrin fibers Pulled the edges of the broken B.V after retraction, to the ultimate state of hemostasis. Failure of clot retraction may indicate to thrombocytopenia.  Prevention of blood clotting in the normal vascular system- intravascular anticoagulants 1. Endothelial Surface Factors 2. Antithrombin Action of Fibrin and Antithrombin III 3. Heparin  Factors that prevent clotting 1- Endothelial Surface Factors: ❑ The smoothness of the endothelial cell surface, which prevents contact activation of the intrinsic clotting system. ❑ A layer of glycocalyx on the endothelium (glycocalyx is a muco-poly-saccharide adsorbed to the surfaces of the endothelial cells), which repels clotting factors and platelets, thereby preventing activation of clotting. ❑ A protein bound with the endothelial membrane,  Thrombomodulin functions Slow the clotting process by capture the thrombin (thrombomodulin-thrombin complex). Thrombomodulin-thrombin complex also activates a protein C, that acts as an anticoagulant by inactivating activated factors V and VIII ❑ When the endothelial wall is damaged: 1. Its smoothness and its glycocalyx & thrombomodulin layer are lost. 2. Activates both factor XII and the platelets 3. Setting off the intrinsic pathway of clotting. ❑ If Factor XII and platelets come in contact with the subendothelial collagen,  2- Antithrombin Action of Fibrin and Antithrombin III: Both fibrin and antithrombin III act as anticoagulants through: ❑ The fibrin fibers that themselves are formed during the process of clotting ❑ An alpha-globulin called antithrombin III or antithrombin-heparin cofactor. 3- Heparin: It is powerful anticoagulant, but its concentration in the blood is normally low. It is produced mast cells & basophil cells. It has little or no anticoagulant properties, but when it combines with antithrombin III, the effectiveness of antithrombin III for removing thrombin increases, and thus it acts as an anticoagulant. The complex of heparin-antithrombin III removes several other activated coagulation factors : Activated factors XII, XI, X, and IX.  Lysis of Blood Clots Plasmin Plasma proteins called plasminogen (pro- fibrinolysin); inactive form. After activated, becomes a plasmin (or fibrinolysin), a proteolytic enzyme. Plasmin digests fibrin fibers and some other protein coagulants such as: fibrinogen, Factor V, Factor VIII, prothrombin, and Factor XII. Its important to remove minute clots from millions of tiny peripheral vessels that eventually would become occluded were there no way to clear them. Conditions That Cause Excessive Bleeding in Human Beings Causes of Bleeding Disorders -Defect in the vessel wall -Platelet deficiency or dysfunction -Derangement of coagulation factors Vitamin K Deficiency Vitamin K is necessary for liver formation of five of the important clotting factors: prothrombin, Factor VII, Factor IX, Factor X, and protein C.  Hemophilia Hemophilia is a bleeding disorder that occurs almost exclusively in males (X-linked recessive inheritance) In female if one of her X chromosomes is deficient, she will be a hemophilia carrier, transmitting the disease to half of her male offspring and transmitting the carrier state to half of her female offspring In 85 % of cases, it is caused by an abnormality or deficiency of Factor VIII; this type of hemophilia is Thrombo-embolism