Anti-thrombotic Flashcards
(28 cards)
What is the most important function of the haemostat system?
To maintain the integrity of the vascular endothelium and blood fluidity
What are the three stages to haemostasis and briefly describe what happens?
Vasoconstriction- reduces size of site of injury
Primary haemostasis- platelet adhesions, shape change, granule release, more recruitment, aggregation
Secondary haemostasis- Tissue factor, phospholipid complex expression, thrombin activation, fibrin polymerisation
What follows haemostasis?
Thrombolysis- once the epithelium heals
What is the haemostat system a balance of?
Maintenance and balance of avoiding blood loss (haemorrhage) and preventing the formation of clots within blood vessels (thrombosis)- Blood fluidity and endothelium integrity
What three things make up a thrombus?
Platelets
Fibrin
Trapped blood cells
What is a partial/total obstruction of a vessel by a thrombus?
Primary thrombosis
What is an embolism?
Migration of a primary thrombus of the cloys to a distant site
What causes a thrombo-emboilism?
Abnormalities of blood flow
Endothelial damage
Hyper coagulability
What can cause endothelial damage?
Trauma Catherisation Neoplasia Parasites Atheroclerosis
What can cause abnormalities of blood flow?
Hypoperfusion, hypervolaemia, heart failure
Compression on blood vessels
Hyperviscocity- dehydration, hyperglobulinaemia
RBCs redcues elasticity
What causes hyper coagulability?
Platelets are hyperaggregatable
Reduces anti-coagulate factors
Hypofibrinolysis
What are the differences between arterial and venous thrombosis?
Arterial- Platlets predominant, therapy against PLT aggregation
Venous- Fibrin and RBCs predominant, therapy against secondary haemostasis
What is used for therapy against platelet aggegation and secondary haemostasis (artery/venous thrombosis)?
Therapy against platelets (artery)- aspirin, clopidogrel
Therapy against secondary (venous)- heparin
How is thrombosis treated?
Dissolution of existing thrombi- surgical extraction, streptokinase, rt-PA, urokinase
How is thrombosis prevented?
Anti-PLT drugs
Heparins
Vitamin K antagonists
rt-PA (recombinant tissue plasminogen activators) what is their action, what are some examples, what is the risk?
Action- enhance the transformation of plasminogen to plasmin
Examples- alteplase, reteplase, tenecteplase
Risk of spontaneous bleeding
What is streptokinase produced by, what is its action and what are its problems?
Produced by B-haemolytic streptococci
Enhances plasmin formation
Can cause a systemic lytic state and production of anti-streptokinase antibodies may be present from streptococci infections
What is the mode of action of urokinase?
Proteasis produced by renal cells and normally present in urine
Activates the plasminogen
How can anti-platlet drugs work?
Cox- inhibitors
ADP-receptro antagonists
Gp IIb/IIa receptor antagonists
What is the mode of action of aspirin, how long do the effects last?
Acts by irreversible acetylation of COX receptor
Causes a reduction in synthesis of thromboxane A2
Effects are permanent and last for the entire platelets life
What is the action of clopidogrel?
Irrevervisle block of the link between ADP and platelet receptor P2Y12
Abnormal activation of receptor GPIIb/IIa
What is the action of unfractionated heparin?
unfractionated heparin binds to Anti-thrombin III and thrombin IIa
and prevents coagulation factors- IXa, Xa, XIa, XIIa
Blocks fibrin formation and platelet activation
What are the pros and cons of unfractionated heparin?
Pros- cheap and widely available
Cons- animals with low anti-thrombin III, pharmacokinetics unpredictable
What is the half life of unfractionated heparin dependent on?
Binds to plasmatic proteins, endothelial cells, macrophages and PLTs so dependent on the half lives of those cells
