Coagulation : Clinical issues
4th Basic Haemato-Pathology Course, TMH, Mumbai
Friday, 30th May 2014
Dr. M.B. Agarwal, MD, MNAMS
Head, Dept of Haematology, Bombay Hospital Inst of Med Sc, Mumbai
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1. Genetic bleeding disorders
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Prakash Kumar : A case study
• Prakash, 15-year old boy from Pune
with post-traumatic nasal bleeding
• No family h/o bleeding disorder
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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
Factor VIII : C
Factor IX
Result
Normal
9%
50 - 150 %
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
2A*
2B*
2M*
2N**
Characteristics
DD
High mol wt VWF
VWD : Type 1 &
multimers absent
Type 2M
Low and High mol wt VWF ↓
↑ RIPA
High mol wt VWF multimers normal
↓ VWF : CB
Markedly ↓ affinity for factor VIII
*VWF : Ag > VWF : RcoF, **AR
Thrombocytopenia
VWD : Type 2A
Haemophilia
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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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Mr. Rajanikant
• Common pathway defect
• Vitamin K deficiency
• Chronic liver disease
• Consumptive coagulopathy
• Anticoagulant therapy
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Mr. Rajanikant
•Genetic disorder : Unlikely
•Vitamin K therapy : No effect
•Liver function : normal
•DIC profile : normal
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Rajanikant : Mixing studies
Test
PT
PTT
Raj
43
56
Control
12
30
4 : 1 mix
15
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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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Rajanikant : Factor assays
Factor I
: 290 mg/dl
Factor II
: 87%
Factor V
: 78%
Factor X
: 1.2%
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Amyloidosis
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Rajanikant : Amyloidosis
• Macroglossia
• S. Protein electrophoresis
• S. Immunofixation
• Bone marrow
• Bone marrow biopsy
: Lambda monoclonal gammopathy
• Abdominal fat pad biopsy
: Amyloidosis
: Faint M band present
: Plasma cells : 2-3%
: 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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What
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
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Thank You
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