Drugs Affecting Coagulation Flashcards
What is thrombosis?
The pathological formation of a haemostatic plug in a blood vessel in the absence of blood loss
What kind of cells are present in a arterial thrombus?
Platelets, white blood cells, fibrin
What kind of cells are present in a venous thrombus?
Platelets, red blood cells, fibrin
What is the first step in haemostasis?
Vasoconstriction - an initial vasoconstriction occurs because of the release of endothelin from the epithelium
What is the second step in haemostasis?
Primary haemostasis - the formation of the initial platelet plug - the exposed collagen in the damaged blood vessel causes platelets to adhere, activate and aggregate
What is the third step in haemostasis?
Secondary haemostasis - activation of the coagulation cascade to convert fibrinogen to fibrin - initiated by the exposure of tissue factor in the damaged endothelium which activates thrombin which converts fibrinogen to fibrin
What is present in the subendothelial ECM which when exposed causes platelets to adhere to the blood vessel?
Von willebrands factor - a factor which binds to platelets via GpIb platelet receptor
What causes platelet activation?
Platelet adhesion (binding to vWF via GpIb), thromboxane A2 and ADP
What happens when platelets are activated?
They release their granule contents (calcium and ADP and serotonin) and synthesise thromboxane A2 and express the GpIIb-IIIa receptor
What is the role of calcium released by platelets?
It is a cofactor in many reactions in the coagulation cascade
What is the role of ADP released by platelets?
It activates other platelets
What is the role of serotonin released by platelets?
vasoconstriction
What is platelet aggregation?
Where fibrinogen binds to GpIIb-IIIa receptors on platelets to form a bridge
How are endothelial cells activated to release tissue factor?
By cytokines such as IL-1 and TNF or by bacterial products such as endotoxin
How is coagulation controlled?
By enzymes which inhibit the cascade e.g. antithrombin or by lysis via plasmin
What are the three factors which lead to thrombosis (Virchow’s triad)?
blood stasis, hyper coagulability, vessel damage
When does blood stasis occur?
in atrial fibrillation or deep vein thrombosis
When does vessel damage occur?
atherosclerosis
What is heparin?
A drug which enhances the activity of antithrombin III (which inhibits factor Xa and thrombin)
What are the pharmacokinetics of heparin?
It has a high molecular weight and is not orally available
What is low molecular weight heparin?
A lower molecular weight version of heparin with less effect on thrombin that has a longer half life - used for patients self administration
What test is used to monitor heparin?
The APTT test (intinsic pathway)
What are the adverse effects of heparin?
haemorrhage, platelet deficiency, osteoporosis
Which factors are vitamin K dependent?
II, VII, IX, X - these factors require gamma carboxylation after synthesis which requires reduced vitamin K as a cofactor
