ANTICOAGULANTS Flashcards
- Blood clot formation - Anticoagulants - Antiplatelets - Thrombolytics
Why is blood clotting not good?
Leads to heart attacks and strokes
What is haemostasis?
It is the prevention of blood loss
What are the four ways in which haemostasis is achieved?
- Vascular constriction
- Formation of a platelet plug
- Formation of a blood clot as a result of blood coagulation
- Eventual growth of fibrous tissue into the blood clot to close the hole in vessel permanently
Why does vascular constriction occur?
Trauma to vessel wall causes smooth muscle to contract which reduces blood flow from ruptured vessel
What are the three factors that cause vascular contraction?
- Nervous reflexes initiated by pain or sensory impulses
- Local myogenic contraction initiated by direct damage to vessel
- Platelets as they release thromboxane A2 which is a vasoconstrictor substance
Structure of a thrombocyte
Thrombocyte = Platelet
- 1-4mm in diameter
- Formed in the bone marrow
- Do not have a nuclei
- Cannot reproduce
- Contain myosin, actin and thrombosthenin allowing platelets to contract
- Residuals of ER and golgi apparatus allowing synthesis of enzymes and storage of large amounts of calcium ions
- Mitochondria and enzyme systems capable of forming ADP and ATP
- Synthesise prostaglandins
- Fibrin-stabilising factor
- Growth factor causing cell growth and helps repair damaged vascular walls
- Membrane contains large amount of phospholipids that activate multiple stages in blood coagulation
- Has a half-life of 8-12 days
- Removed by macrophages
Mechanism of platelet plug formation
- Platelets come into contact with damaged vascular surface or collagen fibres and swell
- Contractile proteins cause forceful contraction which releases granules containing multiple active factors
- This makes them sticky and a protein called von Willebrand factor is leaked into traumatised tissue from plasma
- Large quantities of ADP and TXa2
- These activate nearby platelets and increases their stickiness allowing adherence to original activated platelets
- Platelets attract other platelets forming a loose plug initially and this prevents blood loss
- During blood coagulation, fibrin threads form attaching tightly to platelets
Mechanism of blood coagulation
- Ruptured vessel forms prothrombin activator which in the presence of Ca2+ converts prothrombin to thrombin
- Thrombin acts on fibrinogen forming a fibrin monomer which has a tendency to polymerise and form fibrin fibres
- Thrombin activates fibrin stabilising factor which forms covalent bonds between fibrin monomers and cross linkages between adjacent fibres
- A blood clot is formed
Prothrombin
- Formed continually by the liver
- Vitamin K required for the normal activation
Fibrinogen
- Formed in the liver
- Allows clotting of the interstitial fluid
Where is fibrin-stabilising factor released from?
Platelets and plasma globulins
What is a blood clot?
A meshwork of fibrin fibres running in all directions and entrap blood cells, platelets and plasma
Extrinsic pathway for clotting
- Begins with traumatised wall/extravascular tissue that comes in contact with the blood
1. Release of tissue factor and tissue thromboplastin which contain phospholipids on membrane and composed of lipoprotein complex
2. LPC further complexes with factor VII
3. In the presence of Ca2+ acts on factor X to be activated and form factor Xa
4. This combines with phospholipids and factor V to form prothrombin activator
5. Once clotting begins, thrombin forms which activates factor V in the prothrombin activator complex
Intrinsic pathway for clotting
- Begins with trauma to blood or exposure of blood to collagen
1. Factor XII activated
2. Damaged platelets release platelet phospholipids containing platelet factor 3
3. Factor XII activates Factor XI which requires HMW kininogen
4. Factor XI activates Factor IX
5. Factor IX along with factor VIII, platelet phospholipids and platelet factor 3 activates factor X
6. This combines with phospholipids and factor V to form prothrombin activator
7. Once clotting begins, thrombin forms which activates factor V of prothromin activator complex
Anticoagulant drugs
- Heparin
- Hirudin
- Lepirudin
- Warfarin
