Bleeding Disorders

1. Bleeding Disorders JANUARY 19, 2012 Erin M. Kwolek

2. 3 important questions… Is the bleeding significant? Is the bleeding likely related to an underlying health problem or to medication/chemical ingestion? Is there a family history of a bleeding disorder?

3. Important historical information The nature of bruising Site of bleeding Bleeding with trauma Duration of bleeding tendency General health Drug and chemical ingestion Family history of bleeding

7. hemophilia • Hemophilia • Porphyria • HIV/AIDS • Smallpox • Plague • Cholera • Tuberculosis • Syphillis • Influenza • Malaria • Yellow Fever • Irish Potato Blight

9. Hemophilia Ahistory Talmud – babies did not have to be circumcised if two brothers had died from the procedure 1803 – “hemorrhagic disposition existing in certain families” 1828 - hemophilia

12. Hemophiliaseverity

13. Hemophilia AFactor VIII 1:10,000 Classic hemophilia, Royal disease

15. Hemophilia BFactor iX 1:60,000 Christmas disease

16. Hemophilia treatment Replace missing clotting factors Education and lifestyle On demand vs. Prophylactic

18. Clotting factors in canada

21. Von willebrand Von Willebrand factor is made and stored in endothelial cells Anchors platelets to subendothelium Factor is made up of protein multimers – the more repeating units the “stickier” (more effective) the factor is Stabilizes factor VIII in plasma

23. VW Dx severity TYPE 1 – partial quantitative deficiency • 80% of people with VW Dx have type 1 TYPE 2 – qualitative defect TYPE 3 – virtually complete quantitative deficiency • Very rare • First type described Variable expressivity and incomplete penetrance

24. Von willebrandtreatment Exogenous - Desmopressin • ~3x increase in plasma VWF and factor VIII • Not useful if qualitative abnormality (type 2) • Not useful if complete deficiency (type 3) Endogenous – factors • Plasma derived VWF concentrate – contains VWF and factor VIII

27. Hemorrhagic disease of the newborn Normal PTT, prolonged PT VKDB – early, classic, late Prophylactic Vitamin K Intracranial VKDB

33. < 10 severe mucosal/internal bleeding 10-30 petechiae, purpura, ecchymoses 30-50 easy bruising > 50 asymptomatic

34. Thrombocytopenia Decreased production Increased destruction Abnormal sequestration Normal value – 150-400 x 109/L Lifespan 7-10d

35. Thrombocytopeniadecreased production Toxins/drugs/alcohol Aplastic anemia Intrinsic bone marrow Displacement Nutritional deficiency Hereditary thrombocytopenias

36. ThrombocytopeniaIncreased destruction Auto Immune - ITP

37. Thrombocytopenianon-immune DIC TTP Vasculitis HELLP

38. DIC Activation of coagulation – failure of homeostasis with bleeding and/or thrombosis; consumption of clotting factors and platelets Infection Trauma Abnormal endothelial surface Cancer Obstetrical complications

39. ThrombocytopeniaIncreased sequestration Splenomegaly

40. Platelet dysfunction Congenital causes are rare! • Glanzmann thrombasthenia • Glycoprotein IIb/IIIa • Bernard-Soulier syndrome • Glycoprotein Ib/IX/V Acquired • Drugs • Renal disease • Bone marrow disorders

43. 3 important questions… Is the bleeding significant? Is the bleeding likely related to an underlying health problem or to medication/chemical ingestion? Is there a family history of a bleeding disorder?