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Coagulation : Case based approach

2nd Basic hematopathology course, TMH,

Mumbai

Saturday, 11th June 2011

Dr. M.B. Agarwal, MD, MNAMS

Head, Dept of Haematology, Bombay Hospital Inst of Med Sc,

Mumbai

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Bleeding disorders

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Case 1

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• Jigar, 15-year old boy from Vadodara with

post-traumatic nasal & oral bleeding : 2 hours

• No family h/o bleeding disorder

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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

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Differential diagnosis

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Factor deficiency

or

Inhibitors

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Test Result Control

PTT 46 s 28 s

PTT mix (1:1) 30 s

What does this mean ?

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Factor deficiency

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Test Result Control

PTT 46 s 28 s

PTT mix (1:1) 43 s

What does this mean ?

(46 + 28 = 74 ÷ 2 = 37)

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Inhibitors

Factor specific Lupus type

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Inhibitors

Factor specific Lupus type

• KCT• dRVVT• L1 / L2 > 1.3

• Factor assay

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Normal coagulation cascade

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Intrinsic pathway defect

• Factor VIII deficiency including von Willebrand Disease

• Factor IX deficiency

• Factor XI deficiency (rare)

• Factor XII deficiency (non-bleeder)

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Test Result Normal

Factor VIII : C 9 % 50 - 150 %

Factor IX 77 % 50 - 150 %

What does this mean ?

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Classical haemophilia A

or

von Willebrand Disease

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vWD has equal prevalence in both sexes (Autosomal)

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Coming back to Jigar

• Bleeding from nose

• Raised PTT

• Good correction on mixing studies

• Low factor VIII : C

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Jigar : Further work up

Test Result Normal

VIII : C 9% 50-150%

vWF : Ag 12 % 60-150 %

vWF : RCoF 10 % 50-150 %

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Jigar : Final diagnosis

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Von Willebrand Disease

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vWD : Primary classification

Subtypes vWF

Type 1 Partial deficiency (AD)

Type 2 Qualitative defect (AD)

Type 3 Total deficiency (AR)

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vWD type 2 : sub classification

Subtypes 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

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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)

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Variations in vWF levels ()

• Exercise and stress (adrenaline)

• Infection and inflammation

• Liver disease

• Pregnancy

• Estrogen and progesterone

therapy

• Hyperthyroidism

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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

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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

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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)

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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

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Case 2

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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

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What is the

differential diagnosis ?

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Whenever PT & PTT

both are raised ……?

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First,

we must exclude

difficult collection

(partially clotted blood)

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We must also exclude

effect of high haematocrit

(polycythemia)

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• Common pathway defect

• Vitamin K deficiency

• Chronic liver disease

• Consumptive coagulopathy

• Anticoagulant therapy

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• Liver function : normal

• DIC profile : normal

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Raj : Mixing studies

Test PT PTT

Raj 43 56

Control 12 30

4 : 1 mix 15 35

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Factor I : 290 mg/dl

Factor II : 87%

Factor V : 78%

Factor X : 1.2%

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What is

the aetiology of

selective factor X deficiency

at the age of

69 years ?

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Amyloidosis

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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

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Part 3

Pictorial quiz

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What is

this ?

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Blue toe syndrome

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CoaguloChek

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Conclusion

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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)

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Thank You

Thank You

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QuestionsQuestions

?