Hemostasis - DPT Final PDF

Hemostasis  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...

Hemostasis  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 as a result of blood coagulation, - (4) eventual growth of fibrous tissue into the blood clot to close the hole in the vessel permanently.  1st - Vascular Constriction - Immediately after a blood vessel has been cut or ruptured, the trauma to the vessel wall itself causes the smooth muscle in the wall to contract; - this immediately reduces the flow of blood from the ruptured vessel. - The contraction results from - (1) local myogenic spasm, - (2) local autacoid factors from the traumatized tissues and blood platelets, - (3) nervous reflexes - The nervous reflexes are initiated by pain nerve impulses or other sensory impulses that originate from the traumatized vessel or nearby tissues.  Vascular Constriction - more vasoconstriction probably results from local myogenic contraction of the blood vessels initiated by direct damage to the vascular wall. - for the smaller vessels, the platelets are responsible for much of the vasoconstriction by releasing a vasoconstrictor substance, thromboxane A2. - The more severely a vessel is traumatized, the greater the degree of vascular spasm. - The spasm can last for many minutes or even hours, during which time the processes of platelet plugging and blood coagulation can take place.  2nd - Platelet Plug - If the cut in the blood vessel is very small, the cut is often sealed by a platelet plug - Platelets (thrombocytes) are minute discs 1 to 4 micrometers in diameter - They are formed in the bone marrow from megakaryocytes - 150,000 and 300,000 per microliter - do not have nuclei and cannot reproduce – half-life in the blood of 8 to 12 days - eliminated by the tissue macrophage system in the spleen - CYTOPLASM: Platelets - (1) actin and myosin molecules, which are contractile proteins similar to those found in muscle cells, and thrombosthenin, that can cause the platelets to contract. - (2) residuals of both the ER and the Golgi apparatus that synthesize various enzymes and especially store large quantities of Ca ions. - (3) mitochondria and enzyme systems that are capable of forming ATP and ADP.  Platelets - (4) enzyme systems that synthesize prostaglandins, which are local hormones that cause many vascular and other local tissue reactions; - (5) an important protein called fibrin-stabilizing factor, - (6) a growth factor that causes vascular endothelial cells, vascular smooth muscle cells, and fibroblasts to multiply and grow,causing cellular growth that eventually helps repair damaged vascular walls. - Platelets CELL MEMBRANE: - The cell membrane of the platelets - its surface is a coat of glycoproteins that repulses adherence to normal endothelium - causes adherence to injured areas of the vessel wall, especially to injured endothelial cells - adherence to any exposed collagen from deep within the vessel wall. - the platelet membrane contains large amounts of phospholipids that activate multiple stages in the blood-clotting process - MECHANISM OF PLATELET PLUG - When platelets come in contact with a damaged vascular surface, especially with collagen fibers in the vascular wall, - They begin to swell; they assume irregular forms with numerous irradiating pseudopods protruding from their surfaces; - their contractile proteins contract forcefully and cause the release of granules that contain multiple active factors; - they become sticky so that they adhere to collagen in the tissues and to a protein called von Willebrand factor that leaks from the plasma;  Platelet Plug - they secrete large quantities of ADP; and their enzymes form thromboxane A2. - The ADP and thromboxane act on nearby platelets to activate them, - and the stickiness of these additional platelets causes them to adhere to the original activated platelets - attract more and more additional platelets, thus forming a platelet plug - first a loose plug, but it is successful in blocking blood loss if the vascular opening is small.  Platelet Plug - during the subsequent process of blood coagulation, fibrin threads form - attach tightly to the platelets, thus constructing an solid plug - important for closing minute ruptures in very small blood vessels that occur many thousands of times daily - A person who has few blood platelets develops each day thousands of small hemorrhagic areas under the skin and throughout the internal tissues  3rd - Blood Coagulation - The clot begins to develop in, - 15 to 20 seconds if the trauma to the vascular wall has been severe, - in 1 to 2 minutes if the trauma has been minor - Within 3 to 6 minutes after rupture of a vessel, if the vessel opening is not too large, the entire opening or broken end of the vessel is filled with clot. - After 20 minutes to an hour, the clot retracts; this closes the vessel still further -  Fate of Blood Clot - (1) It can become invaded by fibroblasts, which subsequently form connective tissue all through the clot, - small hole of a vessel wall - complete organization of the clot into fibrous tissue within 1 to 2 weeks - (2) it can dissolve - when excess blood has leaked into the tissues and tissue clots have occurred where they are not needed - Enzymes within the clot itself dissolve the clot  Mechanism of Blood Coagulation - procoagulants and anticoagulants - In the blood stream, the anticoagulants normally predominate, - so thatthe blood does not coagulate while it is circulating in the blood vessels. - But when a vessel is ruptured, procoagulants from the area of tissue damage become “activated” and, - override the anticoagulants, and then a clot develops  General Mechanism - (1) In response to rupture, a complex cascade of chemical reactions occurs in the blood involving many blood coagulation factors. - Thenet result is formation of a complex of activated substances collectively called prothrombin activator. - (2) The prothrombin activator catalyzes conversion of prothrombin into thrombin. - (3) The thrombin acts as an enzyme to convert fibrinogen into fibrin fibers that trap platelets, blood cells, and plasma to form the clot.  Conversion of Prothrombin to Thrombin - the prothrombin activator, in the presence of ionic Ca++, causes conversion of prothrombin to thrombin - the thrombin causes polymerization of fibrinogen molecules into fibrin fibers within another 10 to 15 seconds - rate-limiting factor in causing blood coagulation is usually the formation of prothrombin activator - prothrombin first attaches to prothrombin receptors on the platelets already bound to the damaged tissue -  Clot Retraction - Within a few minutes after a clot is formed, it begins to contract and usually expresses most of the fluid from the clot within 20 to 60 minutes – serum - Platelets become attached to the fibrin fibers in such a way that they tie different fibers together - continue to release fibrin-stabilizing factor, which causes more and more cross-linking bonds - activate thrombosthenin, actin and myosin molecules - contractile proteins  Clot Retraction - The contraction is activated and accelerated by thrombin as well as by, - calcium ions released from calcium stores in the mitochondria, endoplasmic reticulum, and Golgi apparatus of the platelets. - As the clot retracts, the edges of the broken blood vessel are pulled together - contributing still further to the ultimate state of hemostasis  Initiation of Coagulation - Prothrombin activator formed by, - (1) the extrinsic pathway that begins with trauma to the vascular wall and surrounding tissues - (2) the intrinsic pathway that begins with trauma to the blood itself or exposure of the blood to collagen from a traumatized blood vessel wall  Extrinsic Pathway - 1. Release of tissue factor. Traumatized tissue releases a complex of several factors called tissue factor or tissue thromboplastin. - 2. Activation of Factor X. The tissue factor further complexes with blood coagulation Factor VII and, - in the presence of calcium ions, acts enzymatically on Factor X to form activated Factor X (Xa).  Extrinsic Pathway - 3. Effect of activated Factor X (Xa) to form prothrombin activator. - The activated Factor X combines immediately with tissue phospholipids that are part of tissue factor or with additional phospholipids released from platelets as well as with Factor V to form the complex called prothrombin activator. - Within a few seconds, in the presence of calcium ions (Ca++), this splits prothrombin to form thrombin, and the clotting process proceeds. -  Intrinsic Pathway - 1. Blood trauma causes (1) activation of Factor XII and (2) release of platelet phospholipids - When Factor XII is disturbed, such as by coming into contact with collagen or with a wettable surface such as glass, converts it into “activated Factor XII.” - the blood trauma also damages the platelets - andthis releases platelet phospholipids that contain the lipoprotein called platelet factor 3  Intrinsic Pathway - 2. Activation of Factor XI. The activated Factor XII acts enzymatically on Factor XI to activate this factor. - This reaction also requires HMW (high- molecular-weight) kininogen and accelerated by prekallikrein. is - 3. Activation of Factor IX by activated Factor XI. The activated Factor XI then acts enzymatically on Factor IX to activate this factor also.  Intrinsic Pathway - 4. Activation of Factor X. The activated Factor IX, acting in concert with activated Factor VIII and with the platelet phospholipids and platelet factor 3 from the traumatized platelets, activates Factor X. - Factor VIII is the factor that is missing in a person who has classic hemophilia, for which reason it is called antihemophilic factor. - Platelets are the clotting factor that is lacking in the bleeding disease called thrombocytopenia. - 5. Action of activated Factor X to form prothrombin activator. activated Factor X combines with Factor V and platelet or tissue phospholipids to form the complex called prothrombin activator.  Role of Calcium - Except for the first two steps in the intrinsic pathway, calcium ions are required for promotion or acceleration of all the blood-clotting reactions. - In the living body, the calcium ion concentration rarely falls low enough to significantly affect the kinetics of blood clotting. - when blood is removed from a person, it can be prevented from clotting by reducing the calcium ion concentration below the threshold level for clotting, - either by deionizing the calcium by causing it to react with substances such as citrate ion or by precipitating the calcium with substance such as oxalate ion.  Interaction Between the Pathways - the extrinsic pathway can be explosive; With severe tissue trauma, clotting can occur in as little as 15 seconds. - Theintrinsic pathway is much slower to proceed, usually requiring 1 to 6 minutes to cause clotting.  Bleeding - almost all disorders the blood clotting factors are formed by the liver - hepatitis, cirrhosis and acute yellow atrophy - Vitamin K is necessary for liver formation of - prothrombin, Factor VII, Factor IX, Factor X and protein C - Vitamin K is continually synthesized in the intestinal tract by bacteria, so that vitamin K deficiency rarely occurs in the normal person as a result of vitamin K absence from the diet - (except in neonates before they establish their intestinal bacterial flora).  Bleeding - disorders in GI disease, vitamin K deficiency often occurs as a result of poor absorption of fats from the GIT - vitamin K is fat-soluble - failure of the liver to secrete bile into the GIT - obstruction of the bile ducts or liver disease - Inadequate fat digestion and absorption - vitamin K is injected into all surgical patients with liver disease or with obstructed bile ducts 4 to 8 hours before performing the surgical procedure.  Hemophilia - Hemophilia is a bleeding disease that occurs almost exclusively in males. - In 85 per cent of cases - abnormality or deficiency of Factor VIII - hemophilia A or classic hemophilia. - In 15 per cent deficiency of Factor IX.Hemophilia B - Both of these factors are transmitted genetically by way of the female chromosome.  Hemophilia - A woman will never have hemophilia because at least one of her two X chromosomes will have the proper genes. - 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.  Hemophilia - Bleeding usually does not occur except after trauma, - bleeding can often last for days after extraction of a tooth. - Factor VIII has two active components, a large component and a smaller component - The smaller component is most important in the intrinsic pathway for clotting - classic hemophilia. - von Willebrand’s disease - loss of the large component - Rx - injection of purified Factor VIII - costly  Thrombocytopenia - the bleeding is usually from many small venules or capillaries - Small punctate hemorrhages occur throughout all the body tissues. - The skin of such a person displays many small, purplish spots, giving the disease the name thrombocytopenic purpura - bleeding will not occur until the number of platelets in the blood falls below 50,000/µl - Levels as low as 10,000/µl are frequently lethal  Thrombocytopenia - Clot retraction test - idiopathic thrombocytopenia - Autoimmune - Rx – PC, Splenectomy  Thrombi and Emboli - An abnormal clot that develops in a blood vessel is called a thrombus. - Once a clot has developed, continued flow of blood is likely to break it away from its attachment and cause the clot to flow with the blood - freely flowing clots are known as emboli. - emboli that originate in large arteries or in the left side of the heart can flow peripherally and plug arteries or arterioles in the brain, kidneys - Emboli that originate in the venous system or in the right side of the heart generally flow into the lungs to cause pulmonary arterial embolism.  Thromboembolic Conditions - (1) Any roughed endothelial surface of a vessel - caused by arteriosclerosis, infection or trauma is likely to initiate the clotting process. - (2) Blood often clots when it flows very slowly through blood vessels, - where small quantities of thrombin and other procoagulants are always being formed.  Use of t-PA - Genetically engineered t-PA (tissue plasminogen activator) - When delivered directly to a thrombosed area through a catheter, it is effective in activating plasminogen to plasmin, which in turn can dissolve some intravascular clots. - if used within the first hour or so after thrombotic occlusion of a coronary artery, the heart is often spared serious damage.  Thrombosis and Embolism - Clotting always occurs when blood flow is blocked for many hours - the immobility of patients confined to bed - leg veins - the common iliac vein and inferior vena cava - a large part of the clot disengages from its attachments to the vessel wall and flows freely with the venous blood through the right side of the heart - into the pulmonary arteries to cause massive blockage of the pulmonary arteries, called massive pulmonary embolism ------- t-PA therapy  Disseminated Intravascular Coagulation - the clotting mechanism becomes activated in widespread areas of the circulation - presence of large amounts of traumatized or dying tissue in the body that releases great quantities of tissue factor - the clots are small but numerous - widespread septicemia - either circulating bacteria or bacterial toxins (endotoxins) activate the clotting mechanisms. - Plugging of small peripheral vessels greatly diminishes delivery of oxygen and other nutrients to the tissues - leads to or aggravates circulatory shock - septicemic shock – bleeding due to consumption of all factors  Anticoagulants - Heparin - Commercial heparin is extracted from several different animal tissues and prepared in almost pure form. - Injection of 0.5 to 1 mg/k g of body weight, causes the clotting time to increase from a normal of about 6 minutes to 30 or more minutes - immediately preventing or slowing further development of a thromboembolic condition. - The action of heparin lasts about 1.5 to 4 hours - The injected heparin is destroyed by an enzyme in the blood known as heparinase. BLEEDING TIME:1-6 MINS CLOTTING TIME:6-10 MINS PROTHROMBIN TIME:12 SEC