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?
- 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 and anticoagulation factors
3) Blood vessel wall integrity
* Damaged endothelia = blood exposed to procoagulation factors
What does the tissue factor-bearing cell activate?
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.
- Inhibit factor IIa: Dabigatran (oral)
- Inhibit factor Xa: Rivaroxaban (oral)
- Increase activity of AT-III: Heparin (IV, SC) Low-molecular weight heparins (LMWHs) e.g. Dalteparin (parenteral) - preferentially tragets fXa
- 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 (fibrin binds to cross link platlets)
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
