Haematology 3 - Coagulation Flashcards
Recall 4 endogenous anti-coagulants
Anti-thrombin
TFPI
Protein C
Protein S
Recalll 1 procoagulant factors and 3 anticoagulant factor that are synthesised in vascular endothelium
vWF
PGI2
Plasminogen activators (important proteins for activating fibrinolysis)
Thrombomodulin (receptor that is essential for proteinC/S pathway)
Recall the 2 possible mechanisms of platelet activation
- vWF binds to Gp1b which binds to platelets to activate them
- Endothelial Gp1a binds directly to the platelet to activate
Via which receptors do platelets adhere to each other, and what is needed for this to happen?
GpIIb/IIIa using fibrinogen and calcium
Recall one inducer and one inhibitor of platelet aggregation, and the enzyme required for the synthesis of both
Thromboxane A2 increases aggregation
PGI2 inhibits platelet aggregation
COX enzyme
Why does aspirin have an anticoagulant effect?
Irreversibly iInhibits COX enzyme which is necessary for thromboxane A2 production
What is the rate-limiting step in fibrin formation?
Factor Xa
Which clotting factors are vitamin K dependent?
II, VII, IX and X
How does vitamin K activate clotting factors?
Vit K is the co-factor for the gamma decarboxylation of the clotting factors (produced in liver)
Recall 4 factors that promote fibrinolysis
Factor IXa, Xa, TPA and urokinase
These all increase plasmin production which cleaves fibrin
What is the role of plasmin?
Breaks down fibrin in fibriolysis
What is the mechanism of action of heparin?
Augments anti-thrombin effect
What is the role of proteins C and S?
Inactivate Factors 5 and 8
What are the roles of tissue factor and TFPI
Tissue factor activates factor Xa
TFPI neutralises tissue factor
How can platelet and coagulation factor disorders be distinguisghed clinically?
Platelet problems –> immediate superficial bleeding
Coagulation factor deficiencies –> delayed, deep bleeding and haemarthroses
Recall 4 possible causes of ITP
Vancomycin
SLE
Sarcoidosis
Lymphoproliferative disease
Why does DIC cause thrombocytopaenia?
Increased utilisation
How does the presentation of auto-immune thrombocytopaenia differ between children and adults?
In children it tends to be acute whereas it is chronic in adults
How should autoimmune ITP be treated?
Steroids IV Ig (to compete with auto-antibody)
What is the expected APTT and PT results in haemophilia?
APTT prolonged
Normal PT
What is the inheritance pattern of von willebrand disease?
Autosomal dominant
What are the 3 different types of von willebrand disease?
Type 1: partial quantitative deficiency (aut dom)
Type 2: qualitative deficiency (aut dom)
Type 3: complete quantitative deficiency (aut rec)- very similar to haemophilia A because binding of factor8 and vWF protects factor8 from destruction in circulation
Recall some causes of DIC
Sepsis Trauma Cancer Obstetric complications Vascular disorders Reaction to a toxin
What is DIC?
Activation of both coagulation and fibrinolysis causing both thrombosis and bleeding
What is the antidote to heparin?
Protamine sulphate
