Failure of secondary haemostasis Flashcards
What are the 2 main pathways of failure to secondary haemostasis?
- Multiple clotting factor deficiency
- Single clotting factor deficiency
What are some causes of multiple clotting factor deficiency?
- Disseminated intravascular coagulation
- Liver failure
- Vitamin K deficiency
- Warfarin therapy
How can liver failure lead to multiple clotting factor deficiency?
The liver’s hepatocytes are responsible for production of all clotting factors, so failure will lead to loss of production
What is the main cause of single clotting factor deficiency?
- Haemophilia
What is disseminated intravascular coagulation (DIC)?
This is the excessive and inappropriate activation of the haemostatic system (Primary, secondary, fibrinolysis)
What are some causes of DIC?
- Sepsis
- Obstetric emergency
- Malignancy (E.g. prostate cancer)
- Hypovolaemic shock
How does DIC occur?
- Systemic activation of coagulation due to release of procoagulant material (e.g. TF) or via cytokine pathways
- This leads to systemic fibrin generation and deposition, causing thrombosis and organ failure
- This causes consumption of platelets and coagulation factors and activation of fibrinolysis, further causing deficiency
- This means there is a mix of initial thrombosis, followed by a bleeding tendency de to consumption of clotting factors and dysregulated fibrinolysis
What are some complications of DIC?
Microvascular thrombosis formation
Clotting factor consumption
What is the main complication of microvascular thrombus formation?
End organ damage
What are some symptoms of clotting factor consumption?
- Bruising
- Purpura
- Generalised bleeding
What are some tests used in DIC?
- PT, APTT and TT
- FDP testing (D-Dimer)
- FBC
- Blood film
How will PT, APTT and TT be affected in DIC?
They are usually very prolonged, with a markedly reduced fibrinogen level
What will FDP testing show in DIC?
High levels of FDPs, including, D-dimer
Why are D-dimers raised in DIC?
Increased fibrin clot formation leads to intense fibrinolytic activity, causing the breakdown of fibrin into FDPs
What will FBC show in DIC?
Severe thrombocytopenia
What may blood film show in DIC?
Fragmented red blood cells
How is DIC managed?
Management involves treating the underlying cause and then replacement therapy
What does replacement therapy involve in DIC?
- Platelet transfusions
- Plasma transfusions
- Fibrinogen replacement
What is the function of vitamin K on clotting factors?
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
How is vitamin K taken into the body?
Vitamin K is taken in through diet and absorbed in the upper intestine which requires bile salts for absorption
What are some causes of vitamin K deficiency?
- 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)
How will vitamin K deficiency affect PT and APTT?
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
What is haemophilia?
This is an X-linked, hereditary disorder in which there is a deficiency in a single clotting factor
What are the main types of haemophilia?
- Haemophilia A - Factor 8 deficiency
- Haemophilia B - Factor 9 deficiency
- Haemophilia C - Factor 11 deficiency
What is the most common form of haemophilia?
Haemophilia A - It is 5x more common than B
Describe the pathophysiology of haemophiliat?
There is no abnormality of primary haemostasis, but there is a deficiency of secondary haemostasis, leading to bleeding from medium to large blood vessels
How do haemophilia A and B present?
Haemophilia presents with abnormally prolonged bleeding, which recurs episodically at one or a few sites on each occasion
How will haemophilia C present?
Variable bleeding (Not in all patients)
Why does haemophilia C not cause bleeding in everyone?
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
How will a factor 12 deficiency present?
No bleeding - Asymptomatic
Why will a factor 12 deficiency not cause bleeding?
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
What are some clinical features of severe haemophilia A and B?
- Recurrent haemarthroses (Bleeding into joints)
- Recurrent soft tissue bleeds (Bruising in toddlers)
- Prolonged bleeding after dental extractions, surgery and invasive procedures
