Flashcards in Haemostasis and Thrombosis Deck (33)
What percentage of the blood volume is made up of red blood cells?
What normally has to be damaged for a thrombus to form?
What is the difference between red and white thrombi?
Red – forms in veins – rich in fibrin and red blood cells
White – forms in arteries – rich in platelets and macrophages (foam cells)
What are the three parts of Virchow’s triad?
Vessel wall injury
Hypercoagulability/consistency of blood (balance between procoagulants and anti-coagulants)
What are the three stages in the cell based theory of coagulation? State which types of drugs target each of the different stages.
Initiation – small-scale production of thrombin – ANTI-COAGULANTS
Amplification – large-scale thrombin production on the surface of platelets – ANTI-PLATELETS
Propagation – thrombin mediated generation of fibrin strands - THROMBOLYTICS
What does the tissue factor-bearing cell contain?
Prothrombinase Complex = Factor 5a + Factor 10a
Describe the process of initiation.
TF bearing cells activate factor 5 and factor 10 forming the prothrombinase complex (5a + 10a)
The prothrombinase complex converts prothrombin to thrombin
What is responsible for the inactivation of factors 2a and 10a?
State some drugs that target the initiation stage of coagulation.
Low Molecular Weight Heparin (e.g. Dalteparin)
What are the indications of these anti-coagulants?
Venous thromboembolism (DVT + PE)
Prevent thrombosis during surgery
Atrial fibrillation – prophylaxis of stroke
Describe the amplification stage of coagulation.
Thrombin activates platelets and makes them more sticky so that they aggregate
Explain, in detail, how thrombin causes platelet activation.
Thrombin binds to PAR (platelet activated receptor) on the platelet membrane
This causes an increase in intracellular Ca2+ concentration from intracellular stores
This stimulates ADP exocytosis from dense granules
The ADP then binds to P2Y12 receptors (ADP receptor) on the same platelet or on neighbouring platelets, which leads to platelet activation/aggregation
Thrombin binding to the PAR also liberates arachidonic acid The arachidonic acid is converted by COX to thromboxane A2
Thromboxane A2 increases expression of GlpIIb/IIIa (which is involved in platelet aggregation)
State three drugs that target the amplification stage of coagulation and explain how they act.
What are the indications of these anti-platelet drugs?
Arterial thrombosis: Acute coronary syndromes – myocardial infarction Atrial fibrillation – prophylaxis of stroke
Describe the propagation stage of coagulation.
Thrombin converts fibrinogen to fibrin so fibrin strands are generated
Name an important thrombolytic and explain how it acts.
Alteplase – it is a recombinant tissue plasminogen activator (tPA)
Plasminogen is converted to plasmin, which is a protease that degrades fibrin
What are the indications of thrombolytics?
First line treatment for stroke
What is a common site for the formation of deep vein thrombosis?
How can DVT and PE be treated, either prophylactically and after it has happened?
Prophylactically – anticoagulants
After it happens – heparin or low MW heparin
What is an acute coronary syndrome?
Any condition brought on by sudden, reduced blood flow to the heart
What is NSTEMI?
Non-ST elevation myocardial infarction
This is caused by partial occlusion of a coronary artery and it can lead to stable angina
Describe the management of NSTEMI.
Anti-platelets (e.g. clopidogrel and aspirin)
What is STEMI?
ST-elevation myocardial infarction
This is caused by FULL occlusion of a coronary artery
Describe the management of STEMI.
Sometimes thrombolytics if the clot needs to be dissolved
What is IIa
Role of abciximab
Monoclonal antibodies directed at GlpIIb/IIIa
Role of aspirin
Irreversible COX1 inhibitor – it reduces the production of thromboxane by platelets
Role of clopidogrel
Irreversible ADP (P2Y12) receptor antagonist
Role of dabigatran
factor 2a inhibitor