Haemostasis and Thrombosis Flashcards
What percentage of the blood volume is made up of red blood cells?
Around 45%
What normally has to be damaged for a thrombus to form?
Tunica intima
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 foam cells (macrophages that have taken up lipids). Associated with atherosclerosis
What are the three parts of Virchow’s triad?
1) Rate of blood flow
Blood flow is slow/stagnating = no replenishment of anticoagulant factors & balance adjusted in favour of coagulation
2) Consistency of blood
Natural imbalance between procoagulation & anticoagulation factors
3) Blood vessel wall integrity
Damaged endothelia = blood exposed to procoagulation factors
What does the tissue factor-bearing cell contain?
Tissue Factor
Prothrombinase Complex = Factor 5a + Factor 10a
Describe the process of initiation.
TF bearing cells activate factor V and factor X forming the prothrombinase complex (Va + Xa)
The prothrombinase complex converts fII -> IIa (prothrombin to thrombin)
What is responsible for the inactivation of factors IIa and Xa?
Antithrombin (AT-III)
State some drugs that target the initiation stage of coagulation, how they work and how they’re administered.
1) Inhibit factor IIa:
Dabigatran (oral)
2) Inhibit factor Xa:
Rivaroxaban (oral)
3) Increase activity of AT-III:
Heparin (IV, SC)
Low-molecular weight heparins (LMWHs) e.g. Dalteparin (parenteral) - preferentially tragets fXa
4) Inhibits the production of factors II, VII, IX and X:
Warfarin (oral)
Vitamin K epoxide reductase inhibitor
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 (fIIa) activates platelets and makes them change to a stellate shape and become more sticky so that they aggregate
Explain, in detail, how thrombin causes platelet activation.
Thrombin (fIIa) - binds to protease-activated receptor (PAR) on platelet surface.
PAR activation -> rise in intracellular Ca2+
Ca2+ rise -> exocytosis of adenosine diphosphate (ADP) 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
PAR activation -> liberates arachidonic acid (AA)
Cyclo-oxygenase (COX) generates thromboxane A2 (TXA2) from AA
TXA2 activation -> expression of GPIIb/IIIa integrin receptor on platelet surface
GPIIb/IIIa - involved in platelet aggregation
State three drugs that target the amplification stage of coagulation state how they’re administered and explain how they act.
Aspirin (oral) – irreversible COX1 inhibitor – it reduces the production of thromboxane by platelets
Clopidogrel (oral) – irreversible ADP (P2Y12) receptor antagonist
Abciximab (IV,SC) – monoclonal antibodies directed at GlpIIb/IIIa
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
STEMI
What is a common site for the formation of deep vein thrombosis?
Popliteal veins
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.
Anti-platelet drugs
Sometimes thrombolytics if the clot needs to be dissolved
Why is Dabigatran no longer used?
It has a dangerous GI side effect profile.
What does the D-dimer test look for?
Fibrin degradation products
Whats the difference in pharmacological managemnt of DVT and a PE?
PE is more serious
DVT management = Dalteparin interim treatment then rivaroxiban and warfarin
PE management = Dalteparin and heparin interim then rivaroxaban and warfarin
