Clotting Flashcards
What does the endothelium excrete?
Prostacyclin
Nitric oxide
What dies the endothelium secrete?
Mediators like prostaglandins and nitric oxide which prevent platelet adhesion
How doe platelet adhesion occur?
Leads to degranulation of the platelets, releasing ADP
ADP stimulates further platelet aggregation at the site
Platelets synthesise prostaglandin thromboxane A, which causes both vasoconstriction and further aggregation
Receptors on the platelet surface then activate the coagulation cascade, which generates fibrin/platelet thrombus
This is known as primary haemostasis
What occurs after intake of aspirin?
Nuclei of endothelial cells are quickly able to secrete mRNA for the PGI2 production
The enucleate platelets cannot from TXA2, so levels decrease until new platelets are formed in approximately 7 days
How does clopidogrel work?
Works as an ADP receptor antagonist, thus preventing glycoprotein expression and platelet aggregation
What are the causes of reduced platelet production in thrombocytopenia?
Reduced production: Anaplastic anaemia Marrow infiltration Marrow suppression Excess destruction: Immune thrombocytopenia purapura: ITP Other autoimmune causes: SLE, CLL, viruses Thrombotic thrombocytopenia purapura: TTP Haemolytic uraemia syndrome: HUS Sequestration: hyperthyroidism
What is the presentation of thrombocytopenia?
Mucocutaneous bleeding
Bruising/purapura of the skin
Epistaxis/menorrhagia
What is prothrombin time?
Tests the extrinsic pathway, by addition of a tissue factor substitute tot he patient’s plasma
It is prolonged in liver disease, or if the patient is on warfarin
What is international normalised ratio?
Ratio of patient’s PT to a normal control whilst using an international reference preparation (standardises laboratories worldwide)
0.9-1.1 is the normal range
Used for warfarin dosing
What is activated partial thromboplastin time (APTT)?
Addition of a surface activator to the plasma
Tests for intrinsic (contact) pathway
It is the monitoring required for unfractionated heparin (not required for LMWH)
What is thrombin time?
Addition of thrombin to the patient’s plasma
Prolonged with fibrinogen deficiency or abnormal function, or inhibitors such as heparin
What is the coagulation cascade?
Clotting factors are primarily synthesised in the liver and many act as serine proteases to activate other factors
Fibrinogen is factor I
Prothrombin is factor II (thrombin is IIa)
Extrinsic and intrinsic pathway activate a final common pathway that leads to production of fibrin and thus. a thrombus can be formed
At the same time, thrombin, in the presence of calcium ions, activates factor VIII, which stabilises the fibrin clot by cross-linking fibrin molecules
Where is vitamin K found?
leafy green vegetables, dairy products and soya beans
Interstitial flora can also synthesise many forms of vitamin K
It is a cofactor necessary for the production of blood clotting factors:
Factor II, VII, IX, X
What can vitamin K deficiency cause?
Leads to deficiency in clotting factors, leading to an increased PT and haemorrhage
Can arise form malabsorption conditions (fat soluble), cholestatic jaundice (no bile salts), or antibiotics (gut flora disturbances)
What are inhibitors of coagulation?
Anti-thrombin III: serine protease inhibitor, potentiated by heparin
Activated protein C (APC): also generated by vitamin K and activated by thrombin
APC acts with the co-factor protein S to induce fibrinolysis
It destroys factor V and VIII, reducing further thrombin generation and also inhibits stabilisation of the fibrin clot
