Failure of secondary haemostasis

Question 1

What are the 2 main pathways of failure to secondary haemostasis?

Answer 1

• Multiple clotting factor deficiency
• Single clotting factor deficiency

Question 2

What are some causes of multiple clotting factor deficiency?

Answer 2

• Disseminated intravascular coagulation
• Liver failure
• Vitamin K deficiency
• Warfarin therapy

Question 3

How can liver failure lead to multiple clotting factor deficiency?

Answer 3

The liver’s hepatocytes are responsible for production of all clotting factors, so failure will lead to loss of production

Question 4

What is the main cause of single clotting factor deficiency?

Answer 4

• Haemophilia

Question 5

What is disseminated intravascular coagulation (DIC)?

Answer 5

This is the excessive and inappropriate activation of the haemostatic system (Primary, secondary, fibrinolysis)

Question 6

What are some causes of DIC?

Answer 6

• Sepsis
• Obstetric emergency
• Malignancy (E.g. prostate cancer)
• Hypovolaemic shock

Question 7

How does DIC occur?

Answer 7

1. Systemic activation of coagulation due to release of procoagulant material (e.g. TF) or via cytokine pathways
2. This leads to systemic fibrin generation and deposition, causing thrombosis and organ failure
3. This causes consumption of platelets and coagulation factors and activation of fibrinolysis, further causing deficiency
4. This means there is a mix of initial thrombosis, followed by a bleeding tendency de to consumption of clotting factors and dysregulated fibrinolysis

Question 8

What are some complications of DIC?

Answer 8

Microvascular thrombosis formation
Clotting factor consumption

Question 9

What is the main complication of microvascular thrombus formation?

Answer 9

End organ damage

Question 10

What are some symptoms of clotting factor consumption?

Answer 10

• Bruising
• Purpura
• Generalised bleeding

Question 11

What are some tests used in DIC?

Answer 11

• PT, APTT and TT
• FDP testing (D-Dimer)
• FBC
• Blood film

Question 12

How will PT, APTT and TT be affected in DIC?

Answer 12

They are usually very prolonged, with a markedly reduced fibrinogen level

Question 13

What will FDP testing show in DIC?

Answer 13

High levels of FDPs, including, D-dimer

Question 14

Why are D-dimers raised in DIC?

Answer 14

Increased fibrin clot formation leads to intense fibrinolytic activity, causing the breakdown of fibrin into FDPs

Question 15

What will FBC show in DIC?

Answer 15

Severe thrombocytopenia

Question 16

What may blood film show in DIC?

Answer 16

Fragmented red blood cells

Question 17

How is DIC managed?

Answer 17

Management involves treating the underlying cause and then replacement therapy

Question 18

What does replacement therapy involve in DIC?

Answer 18

• Platelet transfusions
• Plasma transfusions
• Fibrinogen replacement

Question 19

What is the function of vitamin K on clotting factors?

Answer 19

Vitamin K is responsible for the final carboxylation of clotting factors II, VII, IX and X (1972), giving them the required negative charge to bind to platelets and form the fibrin clot

Question 20

How is vitamin K taken into the body?

Answer 20

Vitamin K is taken in through diet and absorbed in the upper intestine which requires bile salts for absorption

Question 21

What are some causes of vitamin K deficiency?

Answer 21

• Poor dietary intake
• Malabsorption
• Obstructive jaundice
• Vitamin K antagonists (Warfarin)
• Haemorragic disease of the newborn (babies given vitamin K injection in birth to prevent this)

Question 22

How will vitamin K deficiency affect PT and APTT?

Answer 22

This will caused prolonged prothrombin time and activated partial thromboplastin time (PT tests for tissue factor and factor 7 pathway, while APTT will test for the factor 8 and 9 pathway

Question 23

What is haemophilia?

Answer 23

This is an X-linked, hereditary disorder in which there is a deficiency in a single clotting factor

Question 24

What are the main types of haemophilia?

Answer 24

• Haemophilia A - Factor 8 deficiency
• Haemophilia B - Factor 9 deficiency
• Haemophilia C - Factor 11 deficiency

Question 25

What is the most common form of haemophilia?

Answer 25

Haemophilia A - It is 5x more common than B

Question 26

Describe the pathophysiology of haemophiliat?

Answer 26

There is no abnormality of primary haemostasis, but there is a deficiency of secondary haemostasis, leading to bleeding from medium to large blood vessels

Question 27

How do haemophilia A and B present?

Answer 27

Haemophilia presents with abnormally prolonged bleeding, which recurs episodically at one or a few sites on each occasion

Question 28

How will haemophilia C present?

Answer 28

Variable bleeding (Not in all patients)

Question 29

Why does haemophilia C not cause bleeding in everyone?

Answer 29

Haemophilia will only affect the extrinsic pathway, so thrombin is still activated by the intrinsic pathway to allow this to occur

Thrombin can activate factor 8 and 9, so a factor 11 deficiency will not have the same effect on the common pathway as factor 8 or 9 deficiency will

Question 30

How will a factor 12 deficiency present?

Answer 30

No bleeding - Asymptomatic

Question 31

Why will a factor 12 deficiency not cause bleeding?

Answer 31

Haemophilia will only affect the extrinsic pathway, so thrombin is still activated by the intrinsic pathway to allow this to occur

Thrombin can activate factor 11, so a factor 12 deficiency will have very little effect on the pathway

Question 32

What are some clinical features of severe haemophilia A and B?

Answer 32

• Recurrent haemarthroses (Bleeding into joints)
• Recurrent soft tissue bleeds (Bruising in toddlers)
• Prolonged bleeding after dental extractions, surgery and invasive procedures