Haemostasis and thrombosis Flashcards
What percentage of blood volume is made up by red blood cells?
45%
Where are clotting factors found?
All within the plasma
What is the difference between haemostasis and thrombosis?
Haemostasis- physiological process that prevents excessive blood loss
Thrombosis- Pathophysiological- a blood clot is forming but this doesn’t always involve the rupture of the blood vessel itself
What is thrombosis normally only caused by?
Damage to the tunica intimate- it’s not stopping blood from leaking out because there is no hole in the first place so it’s pathophysiological
What are red thrombi?
Venous clots because they contain lots of erythrocytes and thrombin
What are white thrombi?
Arterial clots- they have a higher platelet component and are white because of macrophages entering the lesion and becoming foam cells
What is virchow’s triad which offers explanations for increased probability of thrombus formation?
Rate of blood flow
Consistency of blood
Vessel wall integrity
Why does rate of blood flow affect risk of thrombus formation?
Slow blood flow increases likelihood of thrombosis
What is slow blood flow a common explanation for?
DVT in legs because BP is very low
What affects the consistency of blood?
Balance between procoagulants and anticoagulants
What are the three main stages of coagulation?
Initiation
Amplification
Propagation
What types of drugs target each stage of coagulation?
Initiation- anticoagulants
Amplification- antiplatelets
Propagation- thrombolytics
Initiation starts with a tissue factor bearing cell, what is on a tissue factor bearing cell?
Tissue factor and prothrombinase complex
What does the prothrombinase complex consist of?
Factor 5a and factor 10a
What does the prothrombinase complex do?
Converts prothrombin (zymogen) to thrombin (active enzyme)
Where is antithrombin (AT-III) found and what does it do?
It is present within the blood and it inactivates factors 2a and 10a
In terms of thrombin generation and breakdown, what happens normally?
Thrombin will be formed by prothrombinase complex and broken down by anti-thrombin
Under pathological conditions, what can happen to thrombin?
Too much thrombin being formed
What is dabigatran?
Factor 2a inhibitor- direct thrombin inhibitor and first oral anticoagulant
What is the problem with dabigatran?
It can cause more bleeding than anticipated
What is rivaroxaban?
Factor 10a inhibitor
Direct inhibitor of factor 10a- also taken orally
What are dabigatran and rivaroxaban classified as?
Novel oral anticoagulant (NOAC)
What does heparin do?
Increases activity of antithrombin (AT-III)
Very effective anticoagulant that can be given IV or SC
What is different about low MW heparin than normal?
It has a longer half life and it activates the portion of antithrombin that is more concerned with breakdown of 10a more so than 2a
What is an example of low MW heparin?
Dalteparin
What does warfarin do?
Vitamin K antagonist- orally active
What is vitamin K important for?
Gamma-carboxylation of factor 2,7,9 and 10 which is important for these to function
When are anticoagulants mainly used?
Treat venous thromboses
During surgery
In atrial fibrillation to prevent stroke
What does thrombin do to platelets?
It interacts with platelets and causes platelet activation
What happens to a platelet when it becomes activated?
The platelet changes shape and becomes more sticky and they aggregate around the area of thrombus formation
What sort of receptors are found on the surface of a platelet?
G protein coupled receptors called protease activated receptors (PAR)
How does thrombin activate platelets?
It binds to PAR
What happens once thrombin binds to PAR?
It causes an increase in intracellular calcium which causes a change in shape of the platelets and also causes exocytosis of ADP
What does ADP do after being exocytosed by a platelet?
It either has an autocrine effect on same platelet or a paracrine effect on neighbouring platelets by binding to P2Y12 receptors (ADP receptors)
What does ADP binding to the ADP receptor cause?
Platelet to become more sticky and more activated which also causes the liberation of arachidonic acid
What happens to arachidonic acid once it is liberated?
It is acted upon by COX to convert it to prostaglandins and thromboxane A2
What does thromboxane A2 do?
It increases the expression of GlpIIb/IIIa on the surface of the platelet- this makes the platelet sticky
What is clopidogrel?
Oral P2Y12 receptor antagonist- prevents platelet activation/aggregation
What is aspirin?
Irreversible COX-1 inhibitor- reduces the production of thromboxane A2
What is abciximab?
Monoclonal antibody that is directed against GlpIIb/IIIa
Why is abciximab not used that often?
Aspirin and clopidogrel are very effective
When are antiplatelets commonly used?
Arterial thrombosis
Acute coronary syndromes- clots in coronary arteries
Atrial fibrillation
What is there large scale production of on the surface of platelets?
Thrombin
What does thrombin do apart from activating platelets?
Converts fibrinogen to fibrin
What does fibrin do?
It traps all the platelets within it like a net
What are thrombolytics also known as?
Clot busters
How do thrombolytics work?
They activate plasmin (anticoagulant factor) which breaks down preformed clots
What is an example of thrombolytic drug?
Alteplase (IV)- A recombinant tissue type plasminogen activator (tPa)
What is the problem with thrombolytics?
They are a little too effective and cause a lot of bleeding- only used in life threatening and dangerous conditions within a certain time period
What are thrombolytics used for?
First line treatment of stroke
STEMI
Where are you most likely to get venous thromboses?
In the popliteal veins where there is stasis
How do you prevent DVT?
Restore the balance and increase amount of anticoagulants:
Prophylactically- anticoagulant drugs
After a PE- heparin or low MW heparin
What is the difference between NSTEMI and STEMI?
NSTEMI- Non-ST elevated myocardial infarction
STEMI- ST elevated myocardial infarction
STEMI is more dangerous
What causes NSTEMI?
Partial occlusion of a coronary artery- can lead to stable angina
What is used to treat NSTEMI?
Antiplatelets
What causes STEMI?
Full occlusion of a coronary artery- causes unstable angina
What is used to treat STEMI?
Anti platelet drugs but in severe cases you may use thrombolytics to dissolve the clot before there is too much damage to the heart muscle
