1. Coagulation Concepts A review of hemostasis Answers are in the notes pages.

2. Hemostasis Outline The big picture

3. Hemostasis is a balancing act! pro - clottinganti - clotting plugs up holes in blood vessels keeps clotting under control

4. PRO-CLOTTING clot

5. Platelets

6. Granules:  (fibrinogen, vWF)  (serotonin, ADP, Ca 2+ ) Membrane: Phospholipids (activate coag factors) GP Ia (binds collagen) GP Ib (binds vWF) GP IIb-IIIa (binds fibrinogen)

7. fibrin clot fibrinogen thrombin prothrombin Xa Va TF VIIa VII TF X IXa IX VIIIa VIII V thrombin Intrinsic Extrinsic COAGULATION CASCADE

8. Aaahhhhh! I can’t tell a Blahnik from a Louboutin!

9. Cruel Shoes

10. TF VII IX VIII fibrin clot thrombin X V IX Intrinsic SEX trinsic PTTPT simple XIa XI XIIa XII thrombin focuses sexy

11. TF VII IX VIII fibrin clot thrombin X V IX SIN trinsic Extrinsic PTTPT simple focuses sexy busy XIa XI XIIa XII thrombin distracts sinful

12. ANTI-CLOTTING clot

13. ANTI-CLOTTING clot 1 cascade inhibition TFPI ATIII Proteins C, S

14. fibrin clot fibrinogen thrombin prothrombin Xa Va TF VIIa VII TF X IXa IX VIIIa VIII V thrombin protein C ATIII TFPI Intrinsic Extrinsic ANTI-CLOTTING

15. clot 1 cascade inhibition TFPI ATIII Proteins C, S 2 clot lysis t-PA plasmin

16. Hemostasis Outline The big picture Laboratory tests

17. Lab Tests: Platelets Count/Morphology at what count do you start bleeding? how often do platelets look weird? Bleeding time measures what? why is it bad? Platelet aggregation studies for which disorders are they helpful?

18. Lab Tests: Coagulation PT/INR which pathway? what makes it go up? PTT which pathway? what makes it go up? what’s an aPTT? what’s the mixing study used for? FDP (D-dimer) assay what would you use this for?

19. TF VII IX VIII fibrin clot thrombin X V FDPs fibrinogen PTTPT TT

20. Hemostasis Outline The big picture Laboratory tests Bleeding disorders

21. Platelet bleeding Factor bleeding Bleeding Disorders: Clinical Features What does each look like?

22. How common is it? How is it transmitted? What is von Willebrand factor? What is the problem? How bad is it? What labs are abnormal? von Willebrand Disease

23. Hemophilia How common is it? How is it transmitted? What is the problem? How bad is it? What labs are abnormal?

24. Bernard-Soulier Glanzmann Grey platelet syndrome δ granule deficiency Matching Hereditary Platelet Disorders No IIb-IIIa No δ granules No Ib No α granules Which ones have big platelets? Which ones have severe bleeding?

25. Disseminated Intravascular Coagulation What causes it? What’s going on in the patient? What does the blood look like? Which labs are abnormal?

26. Other bleeding factoids What are the vitamin-K dependant factors? What causes a decrease in these? Why do patients with liver failure bleed?

27. Hemostasis Outline The big picture Laboratory tests Bleeding disorders Thrombotic disorders

28. Thrombosis risk factors

29. Endothelial damage Stasis Hypercoagulability AtherosclerosisImmobilization Varicose veins Heart stuff Surgery Carcinoma Estrogen Thrombotic disorders

30. When should you start to worry about a thrombotic disorder?

31. Factor V Leiden How common is it? How is it transmitted? What is factor V Leiden? How bad is it? What labs are abnormal?

32. How common are these (relative to factor V Leiden)? What’s the genetic abnormality? How do you diagnose them? Matching Other hereditary thrombotic disorders MTHFR gene Heparin won’t work Usually not serious Gain-of-function mutation Purpura fulminans/ Warfarin induced skin necrosis ATIII deficiency Protein C deficiency Factor II mutation Hyperhomocysteinemia Anti-phospholipid antibodies