Coagulation cascade

Intrinsic pathway (components already present in the blood)

∑ Minor role in clotting
∑ Subendothelial damage e.g. collagen
∑ Formation of the primary complex on collagen by high-molecular-weight kininogen (HMWK), prekallikrein,
and Factor 12
∑ Prekallikrein is converted to kallikrein and Factor 12 becomes activated
∑ Factor 12 activates Factor 11
∑ Factor 11 activates Factor 9, which with its co-factor Factor 8a form the tenase complex which activates
Factor 10

Extrinsic pathway (needs tissue factor released by damaged tissue)

∑ Tissue damage
∑ Factor 7 binds to Tissue factor
∑ This complex activates Factor 9
∑ Activated Factor 9 works with Factor 8 to activate Factor 10

Common pathway
∑ Activated Factor 10 causes the conversion of prothrombin to thrombin
∑ Thrombin hydrolyses fibrinogen peptide bonds to form fibrin and also activates factor 8 to form links
between fibrin molecules

Fibrinolysis
Plasminogen is converted to plasmin to facilitate clot resorption

Intrinsic pathway Increased APTT Factors 8,9,11,12

Extrinsic pathway Increased PT Factor 7

Common pathway Increased APTT & PT Factors 2,5,10

Vitamin K dependent Factors 2,7,9,10

Abnormal coagulation

Cause Factors affected

Heparin Prevents activation factors 2,9,10,11

Warfarin Affects synthesis of factors 2,7,9,10

DIC Factors 1,2,5,8,11

Liver disease Factors 1,2,5,7,9,10

Interpretation blood clotting test results

Disorder APTT PT Bleeding time

Haemophilia Increased Normal Normal

von Willebrand's disease Increased Normal Increased

Vitamin K deficiency Increased Increased Normal

1 Question 1 of 172
Which of the following statements relating to abnormal coagulation is false?

A. Warfarin affects the synthesis of factor 2,7,9,10

B. The prothrombin time is prolonged in Haemophilia A

C. Cholestatic jaundice can cause vitamin K deficiency

D. Disseminated intravascular coagulation is associated with thrombocytopenia

1
 E. Massive transfusion is associated with reduced levels of factor 5 and 8

In haemophilia A the APTT is prolonged and there is reduced levels of factor 8:C. The bleeding time and PT are
normal. Cholestatic jaundice prevents the absorption of the fat soluble vitamin K. Massive transfusion (>10u blood or
equivalent to the blood volume of a person) puts the patient at risk of thrombocytopaenia, factor 5 and 8 deficiency.

2 Question 2 of 172
Which of the following is least likely to cause a prolonged prothrombin time?

A. Cholestatic jaundice

B. Disseminated intravascular coagulation

C. Prolonged antibiotic treatment

D. Liver disease

E. Acquired factor 12 deficiency

Vitamin K deficiency results from cholestatic jaundice and prolonged antibiotic therapy. Acquired factor 12 deficiency
causes prolonged APTT.

3 Question 3 of 172
A 43 year old lady is admitted with cholestasis secondary to a stone impacted at the level of the ampulla of vater.
Which of the following tests is most likely to be predictive of bleeding diathesis at the time of ERCP in this particular
case?

A. Bleeding time

B. Prothrombin time

C. APTT

D. Platelet count

E. Factor I levels

PT: Vitamin K dependent factors 2, 7, 9, 10

APTT: Factors 8, 9, 11, 12

Jaundice will impair the production of vitamin K dependent clotting factors. This is most accurately tested by
measuring the prothrombin time. APTT can be affected by vitamin K deficiency (due to factor 9 deficiency), however
this occurs to a lesser extent and is normally associated with severe liver disease. The bleeding time is a measure of
platelet function.

4 Question 1-3 of 99 January 2012

Theme: Bleeding disorders

A. Vitamin K deficiency
B. von Willebrand's disease
C. Acquired haemophilia
D. Haemophilia B
E. Protein C deficiency
F. Disseminated intravascular coagulation
G. Factor V Leiden
H. Excess heparin
I. Warfarin overdose

2
What is the most likely diagnosis for the scenario given?

1. A 33 year old female is admitted for varicose vein surgery. She is fit and well. After the procedure she is
persistently bleeding. She is known to have menorrhagia. Investigations show a prolonged bleeding time and
increased APTT. She has a normal PT and platelet count.

The correct answer is von Willebrand's disease

Bleeding post operatively, epistaxis and menorrhagia may indicate a diagnosis of vWD. Haemoarthroses are
rare. The bleeding time is usually normal in haemophilia (X-linked) and vitamin K deficiency.

2. A 70 year old coal miner presents with 3 weeks of haematuria and bruising. He is normally fit and well. He is
on no medications. His results reveal:

Hb 9.0; WCC 11; Pl 255

PT 16 (normal); APTT 58 (increased); Thrombin time 20 (normal).

The correct answer is Acquired haemophilia

Factor 8 acquires an inhibitor. The elderly, pregnancy, malignancy and autoimmune conditions are associated
with acquired haemophilia. Prolonged APTT is key to the diagnosis. Management involves steroids.

3. A 33 year old female is attends the day unit for elective varicose vein surgery. She has ly had recurrent
pulmonary embolic events. After the procedure she is persistently bleeding.

Her APTT is 52 (increased).

The correct answer is Factor V Leiden

A combination of thromboembolism and bleeding in a young woman should raise the possibility of
antiphospholipid syndrome. Other features may include foetal loss, venous and arterial thrombosis and
thrombocytopenia. Protein C is not associated with a prolonged APTT.

5 Question 2 of 312
Which of the following is not associated with thrombosis?

A. Endothelial cell damage

B. Use of tourniquets in surgery

C. Formation of platelet aggregates

D. Thrombocytopenia

E. Carcinoma of the stomach

All the other options either act directly to promote thrombosis e.g. endothelial cell damage or via changes in
consistency or flow of blood.

6 Question 37 of 172
Which of the following statements related to the coagulation cascade is true?

A. The intrinsic pathway is the main pathway in coagulation

B. Heparin inhibits the activation of Factor 8

C. The activation of factor 8 is the point when the intrinsic and the extrinsic pathways
meet
D. Tissue factor released by damaged tissue initiates the extrinsic pathway

E. Thrombin converts plasminogen to plasmin

The extrinsic pathway is the main path of coagulation. Heparin inhibits the activation of factors 2,9,10,11. The
activation of factor 10 is when both pathways meet. Thrombin converts fibrinogen to fibrin. During fibrinolysis
plasminogen is converted to plasmin to break down fibrin.

3
7 Question 38 of 172
Which of the following statements about blood clotting is untrue?

A. Platelet adhesion to disrupted endothelium is dependent upon von Willebrand

factor
B. Protein C is a vitamin K dependent substance

C. The bleeding time provides an assessment of platelet function

D. The prothrombin time tests the extrinsic system

E. Administration of aprotinin during liver transplantation surgery prolongs survival

Although aprotinin reduces fibrinolysis and thus bleeding, it is associated with increased risk of death and was
withdrawn in 2007. Protein C is dependent upon vitamin K and this may paradoxically increase the risk of thrombosis
during the early phases of warfarin treatment.