Secondary Hemostasis

• Formation of clot (thrombus).
• Enzymes - active other coagulation factors -most are serine proteases ex II, VII, IX, X, XI, XII, XIII, Prekallikrein
• Cofactors -Amplify the coagulation cascade ex. TF, V, VII and HMWK
• THREE GROUPS OF COAGULATION FACTORS 1. Fibrinogen Group 2. Prothrombin Group 3. Contact Group
• Fibrinogen Group 1. Consist of factors I, V, Vili and XIII
• FIBRINOGEN GROUP

  • These factors are consumed during the process of coagulation.
  • Factor V and VIII are known to decrease during blood storage in vitro.
  • These factors are known to increase during the following: a. Pregnancy b. Inflammation c. Use of oral contraceptive drugs
• Prothrombin Group 1. Consist of factors II, VII, IX and X.
• Prothrombin Group 1. Consist of factors II, VII, IX and X. 2. All these factors are known to be Vitamin K dependent during their synthesis. 3. Vitamin K is available to the body (dietary or bacterial production). 4. Inhibited by warfarin. 5. Stable and well preserved in stored plasma.
• Contact Group 1. Consist of factors XI, XII, prekallikrein and HMWK 2. Involved in intrinsic pathway. 3. Moderately stable. 4. Not consumed during coagulation process.
• Factor I (Fibrinogen) 1. Large and stable globulin with a molecular weight of 341,000. 2. It is the precursor of fibrin. 3. When fibrinogen is exposed to thrombin, two peptides split from the fibrinogen molecule leaving a fibrin monomer. 4. The fibrin monomers aggregate together to form the final fibrin clot.
• Factor II (Prothrombin) 1. Stable protein with a molecular weight of 63,000. 2. With the presence of ionized Calcium, prothrombin is converted to thrombin by the enzymatic action of thromboplastin. 3. Prothrombin has a half-life of almost 3 days with 70% consumption during clotting
• Tissue Thromboplastin (Fomerly Factor III) 1. TT is a term given to any non-plasma substance containing complex from tissues. lipoprotein

  2. TT can be secreted from the following:

  a. Brain

  b. Lungs

  c. Vascular endothelium

  d. Liver

  e. Placenta

  f. Kidneys

  3. These tissue types are capable of converting prothrombin to thrombin.
• Ionized Calcium (Formerly Factor IV) 1. Ionized calcium is necessary for the activation of thromboplastin. 2. IC is the physiologically active form of calcium. 3. Small amount of IC is needed for the activation of coagulation. 4. Calcium deficiency would not be expressed as a coagulation dysfunction, except in cases of massive transfusion.
• Factor V (Proaccelerin) 1. Factor V is extremely labile globulin protein. 2. It has a half-life of 16 hours. 3. Consumed in the clotting process
• Factor VII (Proconvertin) 1. Not essential component of the intrinsic thromboplastin-generating mechanism. 2. It is not destroyed or consumed in clotting and is found in both plasma and serum. 3. The function of Factor VII is the activation of tissue thromboplastin and the acceleration of the production of thrombin from prothrombin. 4. It is reduced by Vitamin K antagonists.
• Factor VIII (Antihemophilic Factor A) 1. It is an acute phase reactant that is consumed during clotting. 2. Not found in serum. 3. Extremely labile: a. 50% loss in vitro at 4 deg. Celsius for 12 hours b. 50% loss in vivo within 8-12 hours after transfusion. 4. Falsely decreased in the presence of Lupus Anticoagulante 5. Endothelial cells are known to synthesize and secrete VIII/VWF multimers.
• Factor IX (Plasma Thromboplastin Component) 1. Stable protein. 2. Its either consumed or destroyed by aging at 4°C for 2 weeks. 3. Essential component of the intrinsic thromboplastic generating system. 4. Influences the amount of thromboplastin than the rate of thromboplastin formation.
• Factor X (Stuart Factor) 1. Stable protein. 2. Not consumed during clotting 3. Together with Factor V. and X in the presence of calcium ions forms the final COMMON PATHWAY 4. The activity of Factor X appears to be related to Factor VII.
• Factor XI (Plasma Thromboplastin Antecedent) 1. Can be found in serum because it is anty partially consumed during clotting process 2. Important in intrinsic thromboplastin generating mechanism
• Factor XII (Hageman Factor) 1. Stable factor. 2. It is not consumed during clotting process. 3. Adsorption of Factor XII and kininogen to subendothelium (collagen) exposed by blood vessel injury initiates the intrinsic coagulation pathway.
• Factor XIII (Fibrin Stabilizing Factor) 1. Fibrin-stabilizing factor in the presence of ionized calcium produces a stabilized fibrin clot. - Fine Fibrin Clots Factor XIII + Calcium ions ↓ Stable Fibrin Clot
• The initiation of the coagulation process may occur via one of two pathways:

  a. INTRINSIC PATHWAY b. EXTRINSIC PATHWAY
• Regardless of the initiating pathway, the two pathways converge into a final COMMON PATHWAY.
• The outcome of the coagulation process is to produce a fibrin clot
• Extrinsic Pathway 1. The EP is initiated by the entry of Tissue Thromboplastio into the circulating blood. 2. Factor Vil binds to Tissue Thromboplastin in the tissue cell membranes and is activated to Factor Vila. 3. Factor Vita is capable of activating Factor X to Factor Xa in the presence of lonized Calcium. 4. Note 5. Factor Vill participates only in the extrinsic pathway.
• Common Pathway 1. Once Factor X is activated to Factor Xa, the extrinsic and intrinsic pathways enter a COMMON PATHWAY. 2. Activation of Factor Xa, it remains platelet bound and activates Factor V. 3. The complex of Factor Xa and Va on the platelet surface will cleave Factor il into THROMBIN (factor lla). 4. It is accelerated by Factor V and Calcium
• Fibrin Formation 1. Clotting is the visible result of the conversion of plasma fibrinogen into stable fibrin clot 2. Thrombin (Factor lia) converts the following: a. Fibrinogen (Factor I) into Fibrin Clot b. Factor Xill to Factor XIIla 3. Fibrinogen is converted into fibrin monomers by thrombin. 4. Fibrin monomers are linked together by Factor Xilla into Fibrin polymers. 5. The fibrin polymers form a meshy network and the final fibrin solution is converted to a gel.
• RETRACTION process is caused by the action of platelets trapped along with RBC and WBC in the clot
• Endothelium and Platelet major site of ihibition
• Protein C- degrades Factor Va and Vlla
• Protein S- degrades Factor Va and Vlla
• Antithrombin III - major inhibitor of thrombin
• Heparin cofactor II -inhibit thrombin
• Alpha 2 Macroglobulin -inhibit activities of thrombin, kallikrein, plasmin
• C1 Inhibitor - inactivator of factor Xila and Kallikrien
• Alpha 1 Antitrypsin - inhibitor of thrombin, Xa and XIa
• Christmas factor is also known as FACTOR 9
• Factor 1 is FIBRINOGEN
• Factor 2 is PROTHROMBIN
• Factor 3 is TISSUE THROMBOPLASTIN