MLAB 1227: Coagulation Keri Brophy -Martinez

1. MLAB 1227: CoagulationKeri Brophy-Martinez Secondary Hemostasis Part Three

2. Extrinsic Pathway Activation • Cell injury releases TF into vasculature • TF provides the phospholipid component where the coagulation factors interact • TF complexes with Ca++ and VIIa to activate X

3. Extrinsic Pathway:Coagulation Factors • Factor III: Tissue Thromboplastin/Tissue Factor (TF) • Manufactured in most body tissues – especially lungs, brain, placenta, RBC membranes. Does not circulate unless damage occurs to tissues • Purpose : • Attracts calcium ions to help the formation of procoagulant enzyme complexes. • Converts prothrombin to thrombin

4. Extrinsic Pathway: Coagulation Factors • Factor VII – Proconvertin (Stabile Factor) • Produced in liver • Vitamin K dependent • Is especially sensitive to Coumadin anticoagulant therapy • Purpose • Activated by tissue thromboplastin(TF)

5. Extrinsic Pathway • Monitored by the Protime (PT) test • Monitors oral coagulation therapy such as coumadin, coumarin • Detects abnormalities in Factor VII, exclusively, but can also pick up deficiencies in the common pathway

6. Common Pathway • Activation of either or both pathways results in the conversion of factor X to Xa • In the common pathway all prothrombin is converted to thrombin, which in turn is converted to fibrin on the phospholipid surface at the site of injury.

7. Common Pathway • Thrombin – enzyme not normally present in plasma. Three functions: • Converts fibrinogen (I) to fibrin (Ia) • Causes potent platelet aggregation • Aids in stabilizing fibrin clot by activating Factor XIII • Activates Protein C to control the extent of clotting

8. Common Pathway: Coagulation Factors • Factor X – Stuart Factor (Stuart-Prower) • Produced in liver • Vitamin K dependent • Activated form acts with V, Ca++ and PF3 to form active thromboplastin

9. Common Pathway: Coagulation Factors • Factor V: Proaccelerin (Labile Factor) • Produced in liver • Deteriorates rapidly in room temperature • Purpose • Essential in thromboplastin formation • Increased in pregnancy & inflammation • Consumed during coagulation, not found in serum

10. Common Pathway: Coagulation Factors • Factor II: Prothrombin • Manufactured in the liver • Vitamin K dependent • Purpose • Upon exposure to V, Xa, PF3 and Ca++, it is converted to thrombin • Stimulates platelet aggregation in presence of Ca++

11. Common Pathway: Formation of Fibrin • Thrombin acts upon fibrinogen (Factor I) to form fibrin (Ia) • Fibrin clot is stabilized by Factor XIII by crosslinking the fibrin polymers

12. Common Pathway:Coagulation Factors • Factor I: Fibrinogen • MW = 341,000 • Normal value in plasma 200-400 mg/dl • Manufactured in the liver • Absent in serum • Purpose • Upon exposure to thrombin, forms fibrin

13. Common Pathway: Coagulation Factors • Factor XIII – Fibrin Stabilizing Factor • Produced in liver and platelets • Necessary to form a stable clot – causes a crosslinking of fibrin monomers

14. Misc: Coagulation Factors • Factor IV: Calcium • Obtained through diet and bone storage • Needed in intrinsic and extrinsic pathways • Removed by citrate • Purpose • Acts as a cofactor in many reactions of the coagulation cascade • Needed for binding to the phospholipid surface, proper platelet function, XIII activation

15. Misc: Coagulation Factors • There is no Factor VI

16. Misc. • All enzymatic reactions require a phospholipid surface, either supplied by the membranes of activated platelets (PF3) or damaged tissues (TF). This phospholipid requirement limits coagulation reactions to the site and prevents clotting.

17. HELP!!! How Will I Ever Get This Down…. 1. Simplified enzymatic coagulation event VIII V XII ----XI---IX------X---------II-------IIa--------I VII

18. Next steps… • Change the sequence to Arabic numerals 8 5 12—11—9—10—2—T –1 7 **”T”= thrombin

19. Learning the PT/PTT Pathways 8 5 12—11—9—10—2—T –1 7 **”T”= thrombin PT PTT

20. Vitamin K Dependant Factors C s s 8 5 12—11—9—10—2—T –1 7 **Think of the central core for those requiring Vitamin K. Protein C and S also require Vitamin K. Protein C inhibits factors 8 and 5. Indicated by “X”

21. Extended Coagulation sequence 8 5 12—11—9—10—2—T –1 7 13

22. Misc. 8 5 12—11—9—10—2—T –1 7 Thrombin sensitive factors Factors destroyed by plasmin Factors found in platelets 13

23. References • McKenzie, Shirlyn B., and J. Lynne. Williams. "Chapter 30." Clinical Laboratory Hematology. Boston: Pearson, 2010. Print.