Year 2 - disorders of coagulation (secondary haemostasis)

Question 1

What is the role of coagulation?

Answer 1

To generate thrombin (factor IIa), which will convert fibrinogen to fibrin

Question 2

What is the result of deficiency in any coagulation factor?

Answer 2

A failure of thrombin generation and hence fibrin formation

Question 3

What are the categories of causes of Coagulation factor deficiencies?

Answer 3

1) Deficiency of coagulation factor production (hereditary/acquired)
2) Dilution (acquired)
3) Increased consumption (acquired)

Question 4

What are the 2 main hereditary coagulation disorders?

Answer 4

Haemophilia A : Factor VIII deficiency

Haemophilia B : Factor IX deficiency

Question 5

What is the prevalence and inheritance pattern of Haemophilia B?

Answer 5

Sex linked -

1 in 10^4 births

Question 6

How are other (much rarer) hereditary coagulation disorders usually inherited?

Answer 6

Very rare

Autosomal recessive

Question 7

What is the effect of haemophilia on secondary hameostasis?

Answer 7

Failure to generate fibrin to stabilise the platelet plug

Question 8

What is the hallmark of haemophilia?

Answer 8

Haemoarthrosis - bleeding into the joint space

Question 9

What are the severities/prognosis of the different coagulation factor deficiencies?

Answer 9

Factor VIII and IX (haemophilia)

• Severe but compatible with life
• Spontaneous joint and muscle bleeding

Prothrombin (Factor II)
Lethal

Factor XI
Bleed after trauma but not spontaneously

Factor XII
No bleeding at all

Question 10

What are the acquired causes that decrease production of coagulation factors?

Answer 10

• Liver failure because most coagulation factors are synthesised in the liver
• Anticoagulant drugs

Question 11

What are the acquired causes that cause dilution of coagulation factors?

Answer 11

-Red cell transfusions no longer contain plasma

Major haemorrhage requires transfusion of plasma as well as red cells and platelets

Question 12

What are the acquired causes that lead to increased consumption of coagulation factors?

Answer 12

Disseminated intravascular coagulation

Question 13

Describe the process of Disseminated intravascular coagulation?

Answer 13

Generalised activation of coagulation - tissue factor
-associated with sepsis, major tissue damage, inflammation
- consumes and depletes coagulation factors
platelets consumed - thrombocytopenia
activation of fibrinolysis depletes fibrinogen - raised D-dimer (a breakdown product of fibrin)
deposition of fibrin in vessels causes organ failure

Question 14

What are the clinical features of coagulation disorders?

Answer 14

superficial cuts do not bleed
bruising is common
nose bleeds are rare
spontaneous bleeding is deep into muscles and joints
bleeding after trauma may be delayed and is prolonged
bleeding frequently restarts after stopping

Question 15

What are the major clinical distinctions between platelet/vascular and coagulation defects?

Answer 15

Platelet/vascular
superficial bleeding into skin, mucosal membranes
Bleeding immediate after injury

Coagulation
bleeding is in deep tissues, muscles, joints

Delayed, but sever bleeding after injury
bleeding is often prolonged

BOTH CAN BE LIFE THREATENING

Question 16

What are the tests for coagulation disorders?

Answer 16

screening tests (‘clotting screen’)

• Prothrombin time
• Activated partial thromboplastin time
• full blood count (platelets)

Coagulation factor assay (e.g. Factor VIII)

Tests for inhibitors