Bleeding Disorders review

2. Bleeding Disordersreview J. Bormanis

3. Bleeding disorders • What are the possibilities • What questions have good yield • What are screening tests • What Lab tests are worrisome and what is the risk

4. Clinical Approach • When did it start ? • Dental history • Spontanous bruising • Bleeding at surgery • Bleeding into joints • Menstrual bleeding • Epistaxis • One site only? Where ? When ?

5. High yield questions • Family history • Pattern of bleeding - where • Difficult to stop or • Re-bleeds • Drug history • Alcohol intake • Co Morbid disease

6. Physical Examination in Bleeding Disorders • Check sites of bleeding • Is it local or generalized ? • what are the manifestations, petichiae, ecchymoses, hematoma ? • Are there vessel wall abnormalities, telangectasia, “palpable purpura, perifollicular hemorrhages” ? • Are there signs of a connective disease process • Are There signs of a systemic disease • The type of bleeding should give a good clue as to which part of hemostasis is affected as well as the severity

7. Laboratory testing • History and physical • Type of tests guided by clinical features • Screening tests • Further tests • Definitive tests

8. Normal Hemostasis

9. Blood Coagulation & Tests Thrombin time

10. Screening Tests • INR Extrinsic pathway • PTT (activated partial thromboplastin time) intrinsic pathway • Thrombin time final pathway • Platelet count • Bleeding time – PFA (not useful)

11. Laboratory tests further testing • INR • PTT • TT thrombin time • Factor assays • Tests of fibrinolysis • platelet count • platelet function tests • Special tests

12. Who is likely to bleed • Obvious • Cirrhosis • Renal dysfunction • Age • Drugs • Right heart failure

13. Inerpretation of tests • If isolated abnormality likely a single defect • eg PTT - possible hemophilia, vWd • If unexplained do mixing test for inhibitor • IF more than one abnormality then more complex • eg. INR and PTT - vitamin K- Coumadin • eg. PTT,TT heparin • eg INR , PTT, TT, Platelets • DIC or liver disease (Cirrhosis) • New anticoagulants Dabigatran, Rivaroxaban

14. Possibilities

15. Clinical Cases

16. Case 1 • It is Friday at 4:40pm • Lab calls • You are patient is being preped for urgent surgery. • INR 6.5 • What to do ?

17. Why INR’s go out of control

18. Vitamin K • Warfarin affects factors II,VII,IX and X • These are the vitamin K dependent factors • Can reverse warfarin effect • Takes time • Available forms ?

19. Efficacy of route of administration

20. Reversing INR wityh vitamin K • Depends on clinical scenario • Complete reversal • Partial reversal (too high INR) • IV or oral forms prefered • For complete reversal 5-10 mg IV q12h for 2 doses will reverse completely in 36-48 hours. • 1-2 mg will decrease INR to therapeutic • Level within 12-24 hrs

22. Current practice

23. Case 2 • You are on call for ENT and are asked to see an 18 year old girl with refractory nosebleed. • The nose is packed and bleeding does not stop. • You notice a few bruises • Blood sent off to lab. • The lab calls at 6:00 Pm with a “critical” platelet count of 10 • What is likely diagnosis • What to do ?

24. ITP Immune thromboctopenic purpura • What is needed for diagnosis • Bone marrow examination • Anti platelet antibodies • When isolated and very low ITP is most likely diagnosis • Could be a part of another disease but not likely (SLE , inf mono) • Does it require hospitalization ?

25. ITP continued • If mucosal bleeding platelets are less than 6 • Needs action • Steroids • IVIG • Anti D • What about splenectomy • New treatments • Rituximab • TPO agonists

26. Case3 • A 48 year old woman appears in emerg with jaundice of 3 weeks duration • Exam – jaundice - some RUQ pain an palpation • Blood tests • CBC Hgb 125, WBC 7.6 Plat 345 • INR 2.6 ptt 42 • What is likely diagnosis • What to Do ?

27. Vitamin K deficiency • Obstructive jaundice • Malabsorption of Vit K dependent factors • Older people at risk • Post surgery at risk • Treatment • Oral or IV Vitamin K

28. Case 4 • A 54 year old male comes to office feeling unwell. • Exam • Mild jaundice, some telangectasis on skin • Mod ascites. • CBC - Hgb 110 WBC 2.5 plat 68 • INR 1.6 Ptt 41 TT 25 • What is likely diagnosis ?

29. Hepatic dysfunction - Cirrhosis • Liver makes and degrades • Coagulation is affected by decreased production and impaired degradation of activated factors • Chronic DIC • Splenomegaly • Trearment only if bleeding • Liver transplant

30. Case 5 • 18 year old male scheduled for tonsillectomy • History of easy bleeding • Exam normal no bruises • CBC normal • INR 1.1 PTT 45 • What is likely diagnosis ? • How to diagnose ?

31. Hemophilia • X linked bleeding disorders characterized by spontaneous development of large hematomes in deep tissues. • May lead to joint bleeding, or into other closed structures • Joint cavity bleeding leads to deformed joints • bleeding may be spontaneous or asssociated with mild or moderate injury

32. Hemophilia types • Hemophilia A • absent or decreased factor VIII • Hemophilia B • lack of factor IX • similar in symptoms to Hemophilia A • Hemophilia A is 10 times more common than hemophilia B

33. Genetics of Factor VIII • Single chain polypeptide • Produced mainly in Liver • remember linked to VWf • Gene deletion - no factor VIII • Point mutation - abnormal factor VIII • Base deletion - Abnormal Factor VIII • Coded on X chromosome -therefore only males affected (transmitted by female carriers)

34. Hemophilia types • Subclassified by level of factors • Levels correspond to clinical symptoms • Mild 5-30% factor activity • Moderate 1-5% activity • Severe <1% activity

35. Hemophilia - Clinical Picture • Mild- do not develop spontaneous bleeding, but do bleed after injury or surgery • Many patients have sever disease • Joint Bleeding results in severe disability • hemarthroses • chronic arthritis • muscle bleeds • Social, economic,psychological problems

36. Case 6 • 17 year old girl with mennorhagia • History of easy bruising • Possible history of easy bruising • CBC normal • INR 1.1 PTT 32 (2 sec prolonged) • What is diagnosis • How to diagnose ? • Treatment ?

37. Von Willebrand’s Disease • Most frequent inherited bleeding disorder • 1% - 1/100 of western population • less severe than hemophilia • Disease results from a decrease or absence of Von Willebrand factor for platelet adhesion • Affects primary hemostasis

38. Von Willebrand’s Disease and Factor VIII • VW factor produced in megakaryocytes and endothelial cells • Coded on chromosome 12 • Autosomal dominant inheritance • Large molecule, and multimeric • Monomers undergoglycolisation and multimerization before secretion • Different multimer size = disease

39. Von Willebrand’s Disease and Factor • VW is carrier for factor VIII • Factor VIII-VWf complex • Factor VIII protein carried in circulation as complex with VWf • Reacts with platelet via GP Ib • Therefore can be problems with platelets and factor VIII

40. Clinical features of Von Willebrand’s Disease • Generally mild bleeding - often unrecognized until surgery or injury • epistaxis, menorrhagia, easy bruising, dental and post operative bleeding • Can be severe in certain types • Requires accurate diagnosis • Requires specific treatment

41. VW -types • Type I • most frequent, quantitave defect (decreased VWf ) • Type II • qualitative defect (abnormal VWf ) • Type III • severe, rare, (absence of VWf )

42. How to diagnose Von Willebrands disease • Clinical history • Factor VIII level • Bleeding time (no longer done) • Measure VWf and perform aggregation tests • Do gel electrophoresis for multimers

43. Anti platelet agents • ASA • Not likelely to create problems • Safer to give if there for cardivascular reasons • Clopidogrel • If elective stop before. • Minimum 3 days • More than 5 days unnecessary

44. Massive bleeding

45. Questions