AHT 1210 Module C1 Hemostasis PDF

AHT 1210 Module C1 Hemostasis Hemostasis: the activation of a series of events that stop the loss of blood whenever blood vessels are damaged - It occurs continuously in all animals to deal with normal wear and tear on the vascular endothelium and also whenever a blood vessel is injured by o...

AHT 1210 Module C1 Hemostasis Hemostasis: the activation of a series of events that stop the loss of blood whenever blood vessels are damaged - It occurs continuously in all animals to deal with normal wear and tear on the vascular endothelium and also whenever a blood vessel is injured by outside trauma Hemostatic Plug Formation: - Normal, intact vascular endothelial cells are thromboresistant. This is achieved because the endothelial cells secrete certain substances - When injury disrupts the endothelial cells, platelets and plasma components are exposed and this activates the hemostatic mechanism - The end result of hemostasis is the formation of the hemostatic plug or clot, which mechanically seals the injury - Hemostatic plug is composed of fibrin, platelets, RBC and WBC 3 major components of hemostasis 1. Vascular 2. Platelet 3. Plasma Vascular Phase Vasoconstriction Release of activator substances Exposure of the subendothelium Vasoconstriction functions to reduce blood When damaged, endothelial cells and other When the endothelium is damaged, the flow to the injured area injured cells release substances involved in collagen in the subendothelium is exposed This reduced blood flow has 2 beneficial fibrinolysis to the blood. effects: 1. The slowed speed of blood flow This results in the activation of the intrinsic promotes platelet adhesion and extrinsic clotting systems 2. It reduces the amount of blood lost Platelet Response Platelet adhesion Platelet activation Platelet aggregation Platelets stick to the subendothelial collagen Change shape which increase surface area ADP and thrombin will attract nearby and basement membrane that is exposed to platelets which stick to the adherent the blood after a vessel is injured Secretes granules which attract other platelets and form the plated plug platelets, causes further vasoconstriction  and influences coagulation Substances that affect platelet aggregation - NSAIDs Acts as a platform for fibrin deposits - Chelating agents (EDTA) Plasma Coagulation Natural anticoagulants and inhibitors Fibrinolysis Component The sequence of reactions involving the When vascular damage occurs, the The mechanism which fibrin are hydrolyzed coagulation factors which result in the hemostatic mechanism is activated, but it is (destroyed) formation of fibrin, an essential component essential that hemostasis is limited to and of the hemostatic plug localized at the site of injury and does not The function of fibrinolysis is to regulate the spread throughout the circulatory system hemostatic mechanism by limiting clot formation and removal of the hemostatic The function of the natural anticoagulants plug as healing occurs and inhibitors is to regulate hemostasis by limiting clot forming - antithrombin and heparin Pathways of the Cascade Sequence Intrinsic Pathway Requires the activation of platelets and coagulation factors Extrinsic Pathway Requires the action of tissue thromboplastin Calcium and vitamin K is also involved in coagulation as it regulates the synthesis of various factors The Common Pathway Both the extrinsic and intrinsic pathways result in the formation of “Thrombokinase” which is actually a group of substances 1. The conversion of prothrombin to thrombin by thrombokinase - This is a very important reaction because thrombin is the most powerful and active enzyme produced by the coagulation reactions 2. The conversion of fibrinogen to fibrin by thrombin Module C2 Thrombopoiesis - Involves the megakaryocytic cell line in the bone marrow, differs from production of other blood cells in that 1. The megakaryocyte get larger as they mature 2. There is no cellular division, rather there is endometriosis within the developing megakaryocytes. This results in clumped, multiple nuclei within the cell 3. The functional end product, which enters the circulation is a cytoplasmic fragment of the megakaryocyte - Platelets or thrombocytes have a lifespan of 8-10 days in circulation Platelet Morphology Peripheral Zone Consists of the plasma membrane and its outer coating the glycocalyx The glycocalyx is important in platelet adhesion Contains coagulation factors Sol-gel Zone Lies just below the plasma membrane and consists of microtubules and microfilaments It also contains contractile proteins and is responsible for cell shape changes Organelle Zone Contains granules which are important in blood blood clotting In dogs up to 25% platelets may be larger than normal Module C3 Disorders Affecting Thrombocytes Thrombocytosis: an increased number of circulating platelets Can be due to: - Splenic contraction (excitement/exercise) - Stress or steroid therapy - Bone marrow disease (rare) Thrombocytopenia: decreased platelet numbers - Common in small animals - Idiopathic - On a CBC, the number of platelets is low and the platelets may be large Causes of thrombocytopenia: 1. Increased utilization - Blood loss - Disseminated intravascular coagulation (DIC) 2. Increased destruction - Immune mediated thrombocytopenia - Circulating anti platelet antibodies destroy platelets - Can be due to drug therapy, infectious disease Impaired Platelet Function 1. Drugs such as NSAIDs, theophylline, furosemide, cephalosporins and estrogen 2. Uremia 3. Von Willebrand disease Tests of Hemostasis - Tests for the vascular and platelet components of hemostasis Buccal Mucosal Bleeding Time (BMBT) - Is a crude screening test that is performed by measuring how long it takes for bleeding to stop from a fresh cut of determined size - A prolonged BMBT indicates: - A platelet disorder - An intrinsic blood vessel problem - Von Willebrand disease - Disorders of the blood vessels are diagnosed by further tests, which rule out platelet abnormalities and vonWillebrand disease Platelet Component - abnormalities in the platelet component can be due to either decreased numbers or abnormal function - Thrombocytopenias are fairly common; they occur as a result of disease or can be immune mediated - Platelet Count (PC) - A platelet estimated is performed as part of the complete blood count (CBC) by the microscopic examination of a stained blood smear - If the platelet estimate indicates an abnormal platelet number, then a platelet count can be done - The blood must be free from platelet clumps Tests for Thrombocytopenia - Bone marrow examination - Platelet function tests  Whole Blood Clotting Time (WBCT) This test is performed by measuring the time it takes for blood to clot once it has been collected into a glass tube Normal is