1. MLAB 1227: C OAGULATION K ERI B ROPHY - M ARTINEZ Secondary Hemostasis Part Three

2. E XTRINSIC P ATHWAY A CTIVATION 1. Cell injury releases TF into vasculature ▫ TF provides the phospholipid component where the coagulation factors interact 2. TF complexes with Ca ++ and VIIa to activate X

3. E XTRINSIC P ATHWAY : C OAGULATION F ACTORS 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. E XTRINSIC P ATHWAY : C OAGULATION F ACTORS 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. E XTRINSIC P ATHWAY 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. C OMMON P ATHWAY 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. C OMMON P ATHWAY Thrombin – enzyme not normally present in plasma. 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 Suppress fibrinolysis

8. C OMMON P ATHWAY : C OAGULATION F ACTORS Factor X – Stuart Factor (Stuart-Prower) Produced in liver Vitamin K dependent Activated form acts with V, Ca ++ and PF 3 to form active thromboplastin

9. C OMMON P ATHWAY : C OAGULATION F ACTORS 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. C OMMON P ATHWAY : C OAGULATION F ACTORS Factor II: Prothrombin Manufactured in the liver Vitamin K dependent Purpose Upon exposure to V, Xa, PF 3 and Ca ++, it is converted to thrombin Stimulates platelet aggregation in presence of Ca ++

11. C OMMON P ATHWAY : F ORMATION OF F IBRIN Thrombin acts upon fibrinogen (Factor I) to form fibrin (Ia) Fibrin clot is stabilized by Factor XIII by crosslinking the fibrin polymers

12. C OMMON P ATHWAY : C OAGULATION F ACTORS 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. C OMMON P ATHWAY : C OAGULATION F ACTORS Factor XIII – Fibrin Stabilizing Factor Produced in liver and platelets Necessary to form a stable clot – causes a crosslinking of fibrin monomers

14. M ISC : C OAGULATION F ACTORS 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. M ISC : C OAGULATION F ACTORS There is no Factor VI

16. M ISC. All enzymatic reactions require a phospholipid surface, either supplied by the membranes of activated platelets (PF 3 ) or damaged tissues (TF). This phospholipid requirement limits coagulation reactions to the site and prevents clotting.

17. HELP!!! H OW W ILL I E VER G ET T HIS D OWN …. 1. Simplified enzymatic coagulation event VIII V XII ----XI---IX------X---------II-------IIa--------I VII

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

19. L EARNING THE PT/PTT P ATHWAYS 8 5 12—11—9—10—2—T –1 7 **”T”= thrombin PT PTT

20. V ITAMIN K D EPENDANT F ACTORS 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. E XTENDED C OAGULATION SEQUENCE 8 5 12—11—9—10—2—T –1 7 13

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

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