Haem: Coagulation Pt.2 Flashcards
How is the common final pathway monitored?
Thrombin time (TT)
Assesses the activity of fibrinogen
Why is the prothrombinase complex important?
It allows activation of prothombin at a much faster rate
What is required for adequate production/absorption of vitamin K?
- Bacteria in the gut produce Vitamin K
- It is fat-soluble so bile is needed for viatmin K to be absorbed
What is the most common cause of vitamin K deficiency?
Warfarin
Name two factors that convert plasminogen to plasmin.
- Tissue plasminogen activator
- Urokinase
Name a factor that inhibits the tissue plasminogen activator and urokinase.
Plasmingoen activtor inhibitor 1 and 2
Name two factors that directly inhibit plasmin.
- Alpha-2 antiplasmin
- Alpha-2 macroglobulin
What is the role of thrombin-activatable fibrinolysis inhibitor (TAFI)?
Inhibitor of fibrin breakdown
Describe the action of antithrombins.
Bind to thrombin in a 1:1 ratio and this complex is excreted in the urine
How many types of antithrombin are there?
Five (antithrombin-III is the most active)
What is the most thrombogenic hereditary condition?
Antithrombin deficiency
Outline the role of protein C and protein S.
- Trace amounts of thrombin generated at the start of the clotting cascade activate thrombomodulin
- This allows protein C to bind to thrombomodulin through the endothelial protein C receptor
- Protein C is then fully activated in the presence of protein S
- Fully activated protein C will inactivate factors 5a and 8a
Why does Factor V Leiden cause a prothrombotic state?
The factor 5a will be resistant to breakdown by protein C.
State two causes of activated protein C resistance.
- Mutated factor 5 (e.g. factor V Leiden)
- High levels of factor 8
What is the role of tissue factor pathway inhibitor?
- TFPI neutralises the tissue factor-factor 7a complex once it has initiated the clotting cascade
List some categories of genetic defects that cause excessive bleeding.
- Platelet abnormalities
- Vessel wall abnormalities
- Clotting factor deficiencies
- Excess clot breakdown
List some acquired defects that cause excessive bleeding.
- Liver disease
- Vitamin K deficiency
- Autoimmune diseases (platelet destruction)
- Trauma
- Anti-coagulants/anti-platelets
List some genetic defects that cause excessive thrombosis.
- Clotting factor inhibitor deficiencies
- Decreased fibrinolysis
List the types of disorders of haemostasis.
- Vascular disorders (e.g. scurvy)
- Platelet disorders
- Coagulation disorders
- Mixed disorders (e.g. DIC)
What is the difference between immediate and delayed bleeding with regards to the underlying pathological process?
- Immediate - issue with the primary haemostatic plug (platelets, endothelium, vWF)
- Delayed - issue with the coagulation cascade
Describe the key clinical differences between platelet disorders and coagulation factor disorders.
Platelet disorders:
- Bleeding from skin and mucous membranes
- Petechiae
- Small, superficial ecchymoses
- Bleeding after cuts and scratches
- Bleeding immediately after surgery/trauma
- Usually mild
Coagulation factor disorders:
- Bleeding into soft tissues, joints and muscles
- No Petechiae
- Large, deep ecchymoses
- Haemarthroses
- No bleeding from cuts and scratches
- Delayed bleeding from surgery or taruma
- Often SEVERE
When is treatment for platelet disorders required?
Platelet count <30x109/L (this is associated with spontaneous haemorrhage)
Why is it important to look at platelets under the microscope in thrombocytopaenia?
- To check whether it is pseudothrombocytopaenia (platelets clump together giving an erroneously low result)
- Also allows identification of other abnormalities (e.g. Grey platelet syndrome - large platelets)
What can cause a decrease in platelet number?
- Decreased producton
- Decreased survival (TTP)
- Increased consumption (DIC)
- Dilution
What can cause defective platelet function?
- Acquired (e.g. aspirin)
- Congenital (e.g. thrombasthenia)
- Cardiopulmonary bypass
