Hemostasis and blood coagulation Lecture by Dr Sandeep :30-10:30 am

The term hemostasis means prevention of blood loss. It is achieved by several mechanisms 1) Vascular constriction 2) Formation of platelet plug 3) Formation of blood clot 4) eventual growth of fibrous tissue in to the blood vessel to close the hole Vascular constriction: Occurs by local myogenic spasm, local autocoid factors, and nervous reflex

Formation of platelet plug Platelets (thromobocytes) are 1-4 micron in diameter. They are formed in the bone marrow from megakaryocytes The normal platelet count is 150,000 to 300,000/microliter Even though they do not have nuclei they contain active factors

Like actin myosin molecules, they are contractile proteins similar in muscle cells The residues of golgi and ER helps in synthesize various enzymes and store large quantity of calcium They also have ATP and ADP They contain prostaglandins Fibrin stabilizing factor is present

It also contain growth factors helps in regrowth of vascular smooth muscle and fibroblasts Mechanism of platelet plug When platelet come in contact with damaged vascular surface, they stick to collagen fibers by changing their shape and character The contractile proteins helps in release of multiple active factors They release ADP and thromoboxane A2 to attract more platelets

Importance of platelet plug formation In day today life numerous microvessels will rupture These holes will be often repaired by platelets In pathological conditions, any decrease in platelet count results in small hemorrhagic spots called “purpura”

Blood coagulation More than 50 important substances that cause or affect blood coagulation Some promote coagulation called “procoagulants” and other inhibit, and they are called as “anticoagulants”

Clotting Factors in Blood and Their Synonyms Clotting Factor Synonyms Clotting Factor Synonyms Fibrinogen-Factor I Fibrinogen-Factor I Prothrombin-Factor II Prothrombin-Factor II Tissue factor-Factor III; tissue thromboplastin Tissue factor-Factor III; tissue thromboplastin Calcium - Factor IV Calcium - Factor IV Factor V-Proaccelerin; labile factor; Factor V-Proaccelerin; labile factor; Factor VII - Serum prothrombin conversion accelerator (SPCA); Factor VII - Serum prothrombin conversion accelerator (SPCA); proconvertin; stable factor proconvertin; stable factor Factor VIII -Antihemophilic factor A Factor VIII -Antihemophilic factor A

Factor IX -Christmas factor; antihemophilic factor B Factor IX -Christmas factor; antihemophilic factor B Factor X -Stuart factor; Stuart-Prower factor Factor X -Stuart factor; Stuart-Prower factor Factor XI - Plasma thromboplastin antecedent (PTA); antihemophilic factor C Factor XI - Plasma thromboplastin antecedent (PTA); antihemophilic factor C Factor XII - Hageman factor Factor XII - Hageman factor Factor XIII -Fibrin-stabilizing factor Factor XIII -Fibrin-stabilizing factor Prekallikrein -Fletcher factor Prekallikrein -Fletcher factor High-molecular-weight kininogen - Fitzgerald factor; HMWK) High-molecular-weight kininogen - Fitzgerald factor; HMWK) Platelets Platelets Protein C Protein C

Clotting takes place in 3 steps 1) Formartion of prothrombin by a complex of activated coagulation factors 2)Prothrombin gets converted into thrombin 3)The thrombin acts as an enzyme to convert fibrinogen into fibrin fibers

Initiation of coagulation Prothrombin activator is generally considered to be formed in two ways 1) By the extrinsic pathways that begins with the trauma to the vascular wall and its surroundings 2) By the intrinsic pathways that begins in the blood itself

Extrinsic pathways It starts with release of tissue factor. The traumatized tissue releases several This factor is composed of phospholipids plus lipoprotein complex

Intrinsic pathways This pathway begins with trauma to the blood itself or exposure of the blood to collagen form the traumatized blood vessel wall

Prevention of blood clotting in blood vessels Normally blood is fluid in the vascular compartment, the most important factor preventing clotting in the normal vascular system are 1) Smoothness of the endothelial cells 2) A layer of glycocalyx on the endothelium, which repels clotting factors and platelets 3) A protein called thrombomodulin which binds thrombin which slows clotting

Condition that causes excessive bleeding in human beings All the clotting factors are formed by the liver therefore, liver disease such as hepatitis, cirrhosis can sometime depress this Defeciency of Vit K –which is imp for synthesis of 5 factors Proteombin, Factor VII, Factor IX, Factor X, and protein C

Defeciency of factor VIII – a condition called hemophilia A Thrombocytopenia