Inherited & Aquired Disorders of Coag. factors

Question 1

Interpret:

a. Prolonged PT
b. Prolonged aPTT
c. Prolonged PT & aPTT

Answer 1

a. deficiency in Extrinsic path (VII, X, V, II, I)
b. deficiency in Intrinsic path (XII, XI, IX, VIII, X, V, II, I)
c. deficiency in Common path (X, V, II, I)

Question 2

Describe principle of Mixing Studies

Answer 2

• if test plasma is prolonged bc missing a factor (=0% functional)
  + normal plasma (=100% fucntional)
  = mixture (=50%)

Question 3

Explain the concept of determining coagulation factor from graph

Answer 3

• clotting time (s) vs factor [ ] (%) on log scale
• 2x lines: test sample - deficient in a factor; normal sample
• The clotting time of each sample is measured at each serial dilution

Question 4

What test do you use to test for acquired pathological inhibitors (Ab of coag. factors) & describe principle

Answer 4

• Bethesda titre test for functional effect
• mix plasma w/ known [ ] of sp. factor & incubate
• amount of inhibitor calculated
• 1 Bethesda unit = inhibitor - inactivate half present in mixture (of equal vol of test & normal)

Question 5

contrast Haemophilia A & B

Answer 5

A: FVIII deficiency => molecular characterisation = detect F8 gene lesions
B: FIX deficiency => molecular characterisation = detect F9 gene lesions

Question 6

What does Haemophilia A & B have in common

Answer 6

• X-linked recessive = Prevalent in males
• prolonged aPTT
• Severe haemophilia (<1% factor)
• Moderate “ (1 -5% factor)
• Mild “ (6 - 30%)

Question 7

Describe fibrinogen deficiency (afibrinogenaemia & severe hypofibrinogenemia)

Answer 7

• common pathway deficit

- prolonged PT, aPTT, TT

Question 8

Describe FVII deficiency (hypoproconvertinaemia)

Answer 8

• Prolonged PT = Extrinsic path deficit

Question 9

pathophysiology of liver disease on aquired factor deficiency

Answer 9

• dec. in pro-coagulant & anti-coag. proteins
  => haemorrhage
  => thrombosis
  => Excess fibrinolysis (10%)

Question 10

Lab assays results expected in liver disease

Answer 10

• PT (& INR) prolonged
• [plt] decreased
• [vWF] inc but ADAMTS13 dec
• Assays for fibrinolysis

Question 11

pathophysiology of Vit K deficiency bleeding (VKBD)

Answer 11

• Low Vit K = pre-cursor proteins made w/out Vit K = not y-carboxylated ≠ not functional bc can’t bind to Ca2+ = non-functional
  caused by lack/poor absorption of Vit K or superwarfarin poisnoing

Question 12

pathophysiology of acquired pathologic inhibitors (incl assay)

Answer 12

• circulating anticoagulants (IgG or IgM)
• commonly to FVIII
• Prolonged test - can’t be corrected by mixing studies
• measured by Bethesda assay