1. Bleeding and Kristine Krafts, M.D. Thrombotic Disorders

2. Bleeding disorders von Willebrand disease Hemophilia A and B DIC TTP/HUS ITP Thrombotic disorders Factor V Leiden Bleeding and Thrombotic Disorders

3. Platelet bleeding Superficial (skin) Petechiae Spontaneous Factor bleeding Deep (joints) Big bleeds Trauma * * Includes prolonged bleeding after dental work

4. Petechiae

5. Palatal petechiae

6. Palatal ecchymosis

7. Purpura

8. Bleeding after buttock injection in patient with hemophilia

9. Bleeding disorders von Willebrand disease Bleeding and Thrombotic Disorders

10. Most common hereditary bleeding disorder Autosomal dominant vW factor decreased (or abnormal) Variable severity Things you must know Von Willebrand Disease

11. Huge multimeric protein Made by megs and endothelial cells Glues platelets to endothelium Carries factor VIII Decreased or abnormal in vW disease What’s von Willebrand Factor?

13. TF VII IX VIII fibrin clot thrombin X V Intrinsic Extrinsic

14. Mucosal bleeding in most patients Deep joint bleeding in severe cases Symptoms of Von Willebrand Disease

15. Bleeding time: prolonged PTT: prolonged (“corrects” with mixing study) PT: normal Lab Tests in Von Willebrand Disease

16. DDAVP (raises VIII and vWF levels) Cryoprecipitate (contains vWF and VIII) Factor VIII Treatment of Von Willebrand Disease

18. fibrinfibrinogen thrombin prothrombin Xa Va TF VIIa VII exposed TF X IXa VIIIa VIII V IX Intrinsic Extrinsic XIa XI thrombin busy distracting sinful SIN trinsic clot

19. Bleeding disorders von Willebrand disease Hemophilia A and B Bleeding and Thrombotic Disorders

20. Most common factor deficiency X-linked recessive in most cases (30% are spontaneous mutations) Factor VIII level decreased Variable amount of “factor” bleeding Things you must know Hemophilia A

25. TF VII IX VIII fibrin clot thrombin X V Intrinsic Extrinsic

26. Deep joint bleeding in patient with hemophilia

27. Hemophilic arthropathy of knee Normal kneeKnee of patient with hemophilia

28. Joint Deformity in Hemophilia

29. Lab tests PTT prolonged Factor VIII level low DNA studies abnormal Treatment DDAVP Factor VIII Hemophilia A

30. Factor IX level decreased Much less common than hemophilia A Same inheritance pattern Same clinical and laboratory findings Things you must know Hemophilia B

31. TF VII IX VIII fibrin clot thrombin X V Intrinsic Extrinsic

32. Bleeding disorders von Willebrand disease Hemophilia A and B DIC Bleeding and Thrombotic Disorders

34. Thrombosis Hemorrhage

35. Malignancy OB complications Sepsis Trauma Remember these for sure:

36. Bleeding disorders von Willebrand disease Hemophilia A and B DIC TTP/HUS Bleeding and Thrombotic Disorders

37. Pentad: MAHA, thrombocytopenia, fever, neurologic defects, renal failure Deficiency of ADAMTS13 Big vWF multimers trap platelets Plasmapheresis or plasma infusions Things you must know Thrombotic Thrombocytopenic Purpura

39. Rodent of unusual size (ROUS) -The Princess Bride, 1987 Von Willebrand multimer of unusual size (MOUS) - NEJM, 1982 Nasty creatures

40. Clinical pentad Hematuria/jaundice (MAHA) Bleeding/bruising (thrombocytopenia) Fever Bizarre behavior (thrombi in CNS) Renal failure (thrombi in kidney) Treatment Plasmapheresis (in acquired TTP) Plasma infusions (in hereditary TTP) Thrombotic Thrombocytopenic Purpura

41. MAHA and thrombocytopenia Most are related to E. coli infection Toxin damages endothelium Treat supportively Things you must know Hemolytic Uremic Syndrome

42. Bleeding disorders von Willebrand disease Hemophilia A and B DIC TTP/HUS ITP Bleeding and Thrombotic Disorders

43. Antiplatelet antibodies coat platelets Splenic macrophages eat platelets Diagnosis of exclusion Steroids or splenectomy Things you must know Idiopathic Thrombocytopenic Purpura

44. Bruising after minor trauma in ITP

45. Bleeding disorders von Willebrand disease Hemophilia A and B DIC TTP/HUS ITP Thrombotic disorders Factor V Leiden Bleeding and Thrombotic Disorders

46. Blood clot sequelae

47. Deep venous thrombosis

49. Pulmonary embolus

50. Endothelial damage Atherosclerosis Stasis Immobilization Varicose veins Cardiac dysfunction Hypercoagulability Surgery Carcinoma Estrogen/postpartum Thrombotic disoders Thrombosis Risk Factors

51. no obvious cause family history weird location recurrent patient is young miscarriages When should you worry about a hereditary disorder?

52. Most common cause of unexplained thromboses Inherited point mutation in factor V gene Factor V can’t be turned off High risk of thrombosis if homozygous Things you must know Factor V Leiden

53. What is Factor V Leiden? A mutated factor V gene Single point mutation Discovered in Leiden, Netherlands Produces abnormal factor V Participates in the cascade Can’t be cleaved by protein C

54. You can turn it on… …but you can’t turn it off ! Yeah, so?

55. TF VII IX VIII fibrin clot thrombin X Va Intrinsic Extrinsic V

56. TF VII IX VIIIa fibrin clot thrombin X Va Intrinsic Extrinsic protein C V VIII

57. Heterozygotes: 7 times normal Homozygotes: 80 times normal Normal risk = 5 per 100,000 person-years! What is the risk of getting a clot?

58. Factor V Leiden Diagnosis PTT and INR not helpful Need genetic testing Treatment Don’t! Unless there is a thrombosis. Then give oral anticoagulants