1. 1 Coagulation : Case based approach 2 nd Basic hematopathology course, TMH, Mumbai Saturday, 11 th June 2011 Dr. M.B. Agarwal, MD, MNAMS Head, Dept of Haematology, Bombay Hospital Inst of Med Sc, Mumbai

2. 2 Bleeding disorders

3. 3 Case 1

4. 4 Jigar, 15-year old boy from Vadodara with post-traumatic nasal & oral bleeding : 2 hours No family h/o bleeding disorder

5. 5 Jigar : Lab. investigations TestsResultsControl Hb13.3 g/dl Haematocrit41.4 % WBC7900/cmm Platelets368,000/cmm PT11 s PTT46 s28 s

6. 6 Differential diagnosis

7. 7 Factor deficiency or Inhibitors

8. 8 TestResultControl PTT46 s28 s PTT mix (1:1)30 s What does this mean ?

9. 9 Factor deficiency

10. 10 TestResultControl PTT46 s28 s PTT mix (1:1)43 s What does this mean ? (46 + 28 = 74 ÷ 2 = 37)

11. 11 Inhibitors Factor specificLupus type

12. 12 Inhibitors Factor specificLupus type KCT dRVVT L1 / L2 > 1.3 Factor assay

13. 13 Normal coagulation cascade

14. 14 Intrinsic pathway defect Factor VIII deficiency including von Willebrand Disease Factor IX deficiency Factor XI deficiency (rare) Factor XII deficiency (non-bleeder)

15. 15 TestResultNormal Factor VIII : C9 %50 - 150 % Factor IX77 %50 - 150 % What does this mean ?

16. 16 Classical haemophilia A or von Willebrand Disease

17. 17 vWD has equal prevalence in both sexes (Autosomal)

18. 18 Coming back to Jigar Bleeding from nose Raised PTT Good correction on mixing studies Low factor VIII : C

19. 19 Jigar : Further work up TestResultNormal VIII : C9%50-150% vWF : Ag12 %60-150 % vWF : RCoF10 %50-150 %

20. 20 Jigar : Final diagnosis

21. 21 Von Willebrand Disease

22. 22 vWD : Primary classification SubtypesvWF Type 1Partial deficiency (AD) Type 2Qualitative defect (AD) Type 3Total deficiency (AR)

23. 23 vWD type 2 : sub classification SubtypesCharacteristicsDD 2A* High mol wt vWF multimers absent vWD : Type 1 & Type 2M 2B* Low and High mol wt vWF ↓ ↑ RIPA Thrombocytopenia 2M* High mol wt vWF multimers normal ↓ vWF : CB vWD : Type 2A 2N**Markedly ↓ affinity for factor VIIIHaemophilia *vWF : Ag > vWF : Rco, **AR

24. 24 vWD : Laboratory tests CBC, platelet count, PT : Normal PTT : often normal Factor VIII (coagulometer) vWF : RCoF (aggregometry) vWF : CB (ELISA) vWF : Ag (ELISA) RIPA : Aggregometry vWF : Multimer analysis (gel electrophoresis)

25. 25 Variations in vWF levels (  ) Exercise and stress (adrenaline) Infection and inflammation Liver disease Pregnancy Estrogen and progesterone therapy Hyperthyroidism

26. 26 Genetic variations in vWF levels Blood group O has lowest level Black race has higher level Black with non A may have double the level of a Caucasian with group O Degree of proteolysis varies ADAMTS-13 activity varies

27. 27 Platelet-type vWD It is not vWD A genetic platelet disorder (AD) A gain-of-function mutation  affinity of platelet GP1b for vWF  RIPA Thrombocytopenia Phenotype : similar to type 2B Treatment : platelet transfusion and not vWF

28. 28 Acquired vWD Not an uncommon disease Pts with autoimmune disorders, hypothyroidism, lymphoma, WM Antibodies are present only in a minority Excessive proteolysis or consumption (AS)

29. 29 Associations Angiodysplastic lesions in gut  Atherosclerosis (pigs) Diagnosis may be totally missed during pregnancy and early puerperium Factor VIII level may vary within the family Role of PFA-100

30. 30

31. 31 Case 2

32. 32 Case study Mr. Raj, 69y from Rajkot SC hematomas & easy bruising : 2 mths Platelet count : 3,32,000/cmm PT : 43/12 secs, INR 3.7 PTT : 56/30 secs

33. 33 What is the differential diagnosis ?

34. 34 Whenever PT & PTT both are raised ……?

35. 35 First, we must exclude difficult collection (partially clotted blood)

36. 36 We must also exclude effect of high haematocrit (polycythemia)

37. 37 Common pathway defect Vitamin K deficiency Chronic liver disease Consumptive coagulopathy Anticoagulant therapy

38. 38 Liver function : normal DIC profile : normal

39. 39 Raj : Mixing studies TestPTPTT Raj4356 Control1230 4 : 1 mix1535

40. 40 Factor I : 290 mg/dl Factor II : 87% Factor V : 78% Factor X : 1.2%

41. 41 What is the aetiology of selective factor X deficiency at the age of 69 years ?

42. 42

43. 43 Amyloidosis

44. 44 Raj : Amyloidosis Macroglossia S. Protein electrophoresis : Faint M band present S. Immunofixation : Lambda monoclonal gammopathy Bone marrow : Plasma cells : 2-3% Bone marrow biopsy : Amyloidosis Abdominal fat pad biopsy : Amyloidosis

45. 45 Part 3 Pictorial quiz

46. 46

47. 47

48. 48

49. 49 What is this ?

50. 50

51. 51

52. 52

53. 53 Blue toe syndrome

54. 54 CoaguloChek

55. 55

56. 56 Conclusion

57. 57 XVIIIth National CME in Haematology & Haemato-oncology on 26 th - 29 th of January 2012 (Thurs - Sun) at Bombay Hospital Inst of Med Sc, Mumbai ( Subsidised registration to participants submitting registration form today)

58. 58 Thank You

59. 59 Questions ?