Disorders of Clotting Cascade

Question 1

Defects of which clotting factors may cause prolonged Prothrombin Time?

Answer 1

Factor I, II, V, VII, X

Question 2

Defects of which clotting factors may cause prolonged Partial Thromboplastin Time?

Answer 2

Factors VIII, IX, X, XI, XII

Question 3

What is von Willebrand’s factor?

Answer 3

Polymer containing collagen and platelet binding sites which allow the two to adhere together. Fibrinogen adheres to platelets causing aggregation in that area by a positive feedback system.

Question 4

Which factor in the coagulation cascade is deficient in Haemophilia A?

Answer 4

Factor VIII

Question 5

What is the epidemiology and genetic link in Haemophilia A?

Answer 5

X linked recessive

Affects 1 in 5000 males

Question 6

What complication can arise from haematomas in Haemophilia A?

Answer 6

Increased pressure can lead to compartment syndrome and nerve palsies

Question 7

What would you expect the blood results of a patient with Haemophilia A to show? (APTT, Factor VIII, PT, Bleeding time, vWF)

Answer 7

APTT = Prolonged
Factor VIII = Reduced
PT, bleeding time, vWF = Normal

Question 8

What is the treatment for bleeding in a patient with Haemophilia A?

Answer 8

Depends how bad the bleed is:

• Mild bleed: Pressure and elevation ± desmopressin (0.3 ug/kg/12hr via IVI over 20 mins)
• Major bleed: Increase Factor VIII levels to 50%
• Life-threatening bleed: Increase Factor VIII levels to 100% by recombinant Factor VIII

Question 9

What action does desmopressin have to stop bleeding in a patient with Haemophilia A?

Answer 9

Promotes production of vWF

Question 10

Why is recombinant Factor VIII preferable in patients with Haemophilia A than plasma-derived Factor VIII?

Answer 10

Hep C and HIV infections have historically been associated with plasma-derived Factor VIII so recombinant is much safer

Question 11

Which factor in the coagulation cascade is deficient in Haemophilia B?

Answer 11

Factor IX

Question 12

What is the epidemiology and genetic link in Haemophilia B?

Answer 12

X linked recessive

Affects 1 in 30,000 males

Question 13

True / False - Desmopressin is effective in Haemophilia B?

Answer 13

False. Desmopressin is only effective in Haemophilia A

Question 14

Describe the different types of von Willebrand’s Disease

Answer 14

Type 1 = Partial deficiency in vWF
Type 2 = Defective vWF
Type 3 = Complete deficiency in vWF

Question 15

Give 3 functions of von Willebrand’s Factor

Answer 15

• Adheres platelets to exposed sub-endothelium
• Binds platelets together
• Attaches to Factor VIII to stop its destruction in the circulation

Question 16

What would you expect the blood results of a patient with Haemophilia A to show? (APTT, PT, bleeding time, vWF, Factor VIII, platelets)

Answer 16

APTT = Prolonged
PT = Normal
Bleeding time = Prolonged
vWF  = Decreased
Factor VIII = Decreased
Platelets = Normal

Question 17

How would you manage a patient with von Willebrand’s Disease?

Answer 17

• Expert help
• Desmopressin in mild bleeding
• vWF with Factor VIII for surgery or major bleeds
• Avoid NSAIDs

Question 18

Why is Vitamin K required for clotting?

Answer 18

Activation of Factor II, VII, IX, X

Question 19

What is the role of ‘antithrombin’ in clotting?

Answer 19

It is a ‘natural anticoagulant’. It’s a serine protease inhibitor. Many coagulation components are serine-based and it acts to inhibit these. Especially active against thrombin (Factor II) and Factor Xa

Question 20

What is the role of Protein C in clotting?

Answer 20

Another ‘natural anticoagulant’. Protein C is activated by thrombin, and the Activated Protein C cleaves Factor V and Factor VIII. Protein C requires a cofactor, Protein S, and these are both Vitamin K dependent.

Question 21

Why is the activity of Protein C and Protein S markedly reduced in Warfarin therapy?

Answer 21

Both are Vitamin K dependent.

Question 22

What is the most common inherited thrombophilia?

Answer 22

Factor V Leiden (or Activated Protein C Resistance)

Question 23

What is Factor V Leiden?

Answer 23

Factor V is normally degraded by Activated Protein C. These patients have an abnormal Factor V (Factor V Leiden) which cannot be so easily degraded by Protein C and thus there is a higher incidence of VTE. Their Factor V is ‘resistant’ to Activated Protein C.