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 Bleeding disorders

3 Case 1

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

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

6 Differential diagnosis

7 Factor deficiency or Inhibitors

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

9 Factor deficiency

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

11 Inhibitors Factor specificLupus type

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

13 Normal coagulation cascade

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

15 TestResultNormal Factor VIII : C9 % % Factor IX77 % % What does this mean ?

16 Classical haemophilia A or von Willebrand Disease

17 vWD has equal prevalence in both sexes (Autosomal)

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

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

20 Jigar : Final diagnosis

21 Von Willebrand Disease

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

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

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 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 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 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

31 Case 2

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 What is the differential diagnosis ?

34 Whenever PT & PTT both are raised ……?

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

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

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

38 Liver function : normal DIC profile : normal

39 Raj : Mixing studies TestPTPTT Raj4356 Control : 1 mix1535

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

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

42

43 Amyloidosis

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 Part 3 Pictorial quiz

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49 What is this ?

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53 Blue toe syndrome

54 CoaguloChek

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56 Conclusion

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 Thank You

59 Questions ?