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1 Coagulation : Clinical issues Dr. M.B. Agarwal, MD, MNAMS Head, Dept of Haematology, Bombay Hospital Inst of Med Sc, Mumbai 4 th Basic Haemato-Pathology Course, TMH, Mumbai Friday, 30 th May 2014
2 1. Genetic bleeding disorders
3 Prakash, 15-year old boy from Pune with post-traumatic nasal bleeding No family h/o bleeding disorder Prakash Kumar : A case study
4 Prakash Kumar: Lab investigations TestsResultsControl Hb13.3 g/dl Haematocrit41.4 % WBC7900/cmm Platelets368,000/cmm PT11 s PTT46 s28 s
5 Differential diagnosis
6 Factor deficiency or Inhibitors
7 TestResultControl PTT46 s28 s PTT mix (4:1)30 s
8 Factor deficiency
9 Normal coagulation cascade
10 Intrinsic pathway defect Factor VIII deficiency including Von Willebrand Disease Factor IX deficiency Factor XI deficiency (rare) Factor XII deficiency (non-bleeder)
11 TestResultNormal Factor VIII : C9 %50 - 150 % Factor IX77 %50 - 150 % What does this mean ?
12 Classical haemophilia A or Von Willebrand Disease
13 VWD has equal prevalence in both sexes (Autosomal)
14 Prakash Kumar : A case study Bleeding from nose Raised PTT Good correction on mixing studies Low factor VIII : C
15 Prakash Kumar : Further work up TestResultNormal VIII : C9%50-150% VWF : Ag12 %60-150 % VWF : RCoF10 %50-150 %
16 Prakash Kumar : Final diagnosis
17 Von Willebrand Disease
18 VWD : Primary classification SubtypesVWF Type 1Partial deficiency (AD) Type 2Qualitative defect (AD) Type 3Total deficiency (AR)
19 VWD type 2 : sub classification SubtypesCharacteristicsDD 2A* High mol wt VWF multimers absent VWD : Type 1 & Type 2M 2B* Low and High mol wt VWF ↓ ↑ RIPA Thrombocytopenia 2M* High mol wt VWF multimers normal ↓ VWF : CB VWD : Type 2A 2N**Markedly ↓ affinity for factor VIIIHaemophilia *VWF : Ag > VWF : RcoF, **AR
20 Prakash Kumar : Final diagnosis
21 Von Willebrand Disease – Type 1
22 2. Acquired bleeding disorders
23 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
24 How do you approach a case with both raised PT & PTT ?
25 First, we must exclude difficult collection (partially clotted blood)
26 We must also exclude effect of high haematocrit (polycythemia)
27 Normal coagulation cascade
28 We should now consider a single genetic factor deficiency from common pathway or multiple factor deficiencies from both pathways
29 Common pathway defect Vitamin K deficiency Chronic liver disease Consumptive coagulopathy Anticoagulant therapy Mr. Rajanikant
30 Genetic disorder : Unlikely Vitamin K therapy : No effect Liver function : normal DIC profile : normal Mr. Rajanikant
31 Rajanikant : Mixing studies TestPTPTT Raj4356 Control1230 4 : 1 mix1534 Conclusion : Factor deficiency
32 Common pathway defect Factor I deficiency Factor II deficiency Factor V deficiency Factor X deficiency
33 Factor I : 290 mg/dl Factor II : 87% Factor V : 78% Factor X : 1.2% Rajanikant : Factor assays
36 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
37 3. Pictorial Quiz
39 What is this ?
40 What is this ?
48 What is it?
53 Blue toe syndrome
57 Bleeding at 6 pm on left forearm
58 Factitious purpura
59 Thank You
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