1

Coagulation : Case based approach 2nd Basic hematopathology course, TMH, MumbaiSaturday, 11th June 2011

Dr. M.B. Agarwal, MD, MNAMSHead, Dept of Haematology, Bombay Hospital Inst of Med Sc, Mumbai

2Bleeding 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

Tests Results Control

Hb 13.3 g/dl

Haematocrit 41.4 %

WBC 7900/cmm

Platelets 368,000/cmm

PT 11 s 11 s

PTT 46 s 28 s

6

Differential diagnosis

7

Factor deficiencyor

Inhibitors

8

Test Result Control

PTT 46 s 28 s

PTT mix (1:1) 30 s

What does this mean ?

9

Factor deficiency

10

Test Result Control

PTT 46 s 28 s

PTT mix (1:1) 43 s

What does this mean ?(46 + 28 = 74 ÷ 2 = 37)

11

Inhibitors

Factor specific Lupus type

12

Inhibitors

Factor specific Lupus 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

Test Result Normal

Factor VIII : C 9 % 50 - 150 %

Factor IX 77 % 50 - 150 %

What does this mean ?

16

Classical haemophilia Aor

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

Test Result Normal

VIII : C 9% 50-150%

vWF : Ag 12 % 60-150 %

vWF : RCoF 10 % 50-150 %

20

Jigar : Final diagnosis

21

Von Willebrand Disease

22

vWD : Primary classification

Subtypes vWF

Type 1 Partial deficiency (AD)

Type 2 Qualitative defect (AD)

Type 3 Total deficiency (AR)

23

vWD type 2 : sub classificationSubtypes Characteristics DD

2A* High mol wt vWF multimers absent

vWD : Type 1 & Type 2M

2B*Low and High mol wt vWF ↓

↑ RIPAThrombocytopenia

2M*High mol wt vWF multimers normal

↓ vWF : CBvWD : Type 2A

2N** Markedly ↓ affinity for factor VIII Haemophilia

*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 excludeeffect 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

Test PT PTT

Raj 43 56Control 12 30

4 : 1 mix 15 35

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

46

47

48

49

What is this ?

50

51

52

53

Blue toe syndrome

54

CoaguloChek

55

56

Conclusion

57

XVIIIth National CME in Haematology & Haemato-oncology on

26th - 29th of January 2012 (Thurs - Sun)at

Bombay Hospital Inst of Med Sc, Mumbai

( Subsidised registration to participants submitting registration form today)

58Thank You

59

Questions

?