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Coagulation : Clinical issues

Dr. M.B. Agarwal, MD, MNAMS

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

Mumbai

4th Basic Haemato-Pathology Course, TMH, Mumbai

Friday, 30th May 2014

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1. Genetic bleeding disorders

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•Prakash, 15-year old boy from Pune

with post-traumatic nasal bleeding

•No family h/o bleeding disorder

Prakash Kumar : A case study

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Prakash Kumar: 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 (4:1) 30 s

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Factor deficiency

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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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Prakash Kumar : A case study

•Bleeding from nose

•Raised PTT

•Good correction on mixing studies

•Low factor VIII : C

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Prakash Kumar : 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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Prakash Kumar : 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 : RcoF, **AR

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Prakash Kumar : Final diagnosis

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Von Willebrand Disease – Type 1

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2. Acquired bleeding disorders

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Case study

•Mr. Rajanikant, 69 y from Mumbai

•SC hematomas & easy bruising : 2 mths

•Platelet count : 3,32,000/cmm

•PT : 43/12 secs, INR 3.7

•PTT : 56/30 secs

•Both PT & PTT are raised

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How do you approach a case with

both raised PT & PTT ?

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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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Normal coagulation cascade

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We should now consider a single

genetic factor deficiency from

common pathway or multiple

factor deficiencies from both

pathways

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• Common pathway defect

• Vitamin K deficiency

• Chronic liver disease

• Consumptive coagulopathy

• Anticoagulant therapy

Mr. Rajanikant

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•Genetic disorder : Unlikely

•Vitamin K therapy : No effect

•Liver function : normal

•DIC profile : normal

Mr. Rajanikant

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Rajanikant : Mixing studies

Test PT PTT

Raj 43 56

Control 12 30

4 : 1 mix 15 34

Conclusion : Factor deficiency

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Common pathway defect

•Factor I deficiency

•Factor II deficiency

•Factor V deficiency

•Factor X deficiency

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Factor I : 290 mg/dl

Factor II : 87%

Factor V : 78%

Factor X : 1.2%

Rajanikant : Factor assays

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Amyloidosis

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Rajanikant : 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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3. Pictorial Quiz

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What is

this ?

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What is this ?

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Wha

t is

it?

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Blue toe syndrome

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CoaguloChek

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Bleeding at 6 pm

on

left forearm

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Factitious

purpura

59Thank YouThank You