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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
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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 deficiencyor
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 Aor
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 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
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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 excludeeffect 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 56Control 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)
58Thank You
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Questions
?