PH1124- Haemostasis Flashcards
what does haemostasis mean ?
Haemo- blood
stasis - stop
The stopping of a flow of blood
what does anticoagulant mean ?
having the effect of retarding or inhibiting the coagulation of the blood.
What is primary haemostasis?
The process of forming the platelet plug is called primary haemostasis
Damage to the endothelium results in a reduction in the release of inhibitory mediators and exposure of the underlying negatively charged tissue matrix to blood components. The initial haemostatic response is to generate a platelet plug. A platelet plug is a relatively weak structure but can be sufficient to stabilise and allow the repair of small injuries to the vascular wall.
Following initiation of the haemostatic process by damage to the vascular wall, there are a number of immediate responses that happen simultaneously. The first is localised vasoconstriction which helps to reduce blood flow through the affected vessel to reduce loss and concentrate haemostatic mediators in the area of damage. The other two mechanisms are platelet adhesion to the damaged vascular wall and platelet aggregation, where they stick together forming a platelet plug. If the platelet plug is a sufficient scaffold to protect the tissue as it repairs, haemostasis does not progress any further. If insufficient, the process progresses into secondary haemostasis and the formation of a tough fibrous clot.
What is secondary haemostasis ?
The formation of the stronger fibrous clot is called secondary haemostasis. Secondary haemostasis is simply a continuation of the primary haemostatic process.
What is the process of vasoconstriction in depth ?
Vascular tissue contracts in response to damage. In part, this is mediated via a loss of vasorelaxant tone due to damage to the endothelium, it is also mediated by a contractile response to damage in the smooth muscle itself. Damage also activates sensory nerves embedded in the vascular wall that release peptide neurotransmitters that are powerful vasoconstrictor agents. Finally, platelets that interact with the exposed tissue matrix underneath the endothelium become activated and release thromboxane A2 that is another powerful vasoconstrictor.
The aim of the vasoconstriction in the area of damage is to redirect flow elsewhere, by increasing resistance to flow, thereby reducing blood loss. The reduction in flow through the affected area also increases the concentration of pro-thrombotic mediators in the area of damage. Lastly, a reduction in flow reduces the shear stress forces on the newly forming platelet plug.
What is the approximate normal platelet count ?
• Normal platelet count is 150-400 x 109/L
Describe initiation of platelet activation and
Primary initiation of platelet activation occurs when receptors located on the plasma membrane of platelets encounter collagen or Von Willebrand’s factor that is located beneath the endothelial vascular lining. Damage to the endothelium exposes these proteins to platelets resulting in activation of this first wave. Activated platelets then release a raft of mediators that activate surface receptors on other platelets leading to their activation. These are receptors such as the P2Y receptor are important targets to intervene in the haemostatic cascade and you will certainly hear more about them in the second Year.
In addition to releasing mediators that activate other platelets, activation leads to the activation of glycoprotein IIb-III on the platelet surface. This receptor binds fibrinogen and aids in linking platelets together to form the platelet plug.
What are the three steps in platelet aggregation ? (binding together)
- ADP released from platelet cytoplasm upon adherence induces exposure of fibrinogen receptors (GPIIb/IIIa receptor)
- Fibrinogen binds to the exposed GPIIb/IIIa receptors
- Extracellular Ca2+-dependent fibrinogen bridges link adjacent platelets
what are the inhibitory mediators ?
- ENDOTHELIAL synthesis of prostacyclin (PGI2) and nitric oxide (NO)
- Causes vasodilation and inhibits platelet aggregation
- ENDOTHELIAL production of plasminogen activator
- Promotes removal of clots
- ENDOTHELIAL expression of thrombomodulin
- Alters thrombin conformation: non-aggregatory + activates anticoagulant factors (protein C)
• ENDOTHELIAL barrier to underlying tissue matrix
- Activation of aggregation stimulated by –ve charge of collagen matrix
- ENDOTHELIAL expression of antithrombin III (AT-III) + heparin sulphate proteoglycans
- Inhibits thrombin and factor Xa – both key elements in haemostatic response.
- Activity increased by heparin sulfate proteoglycans present on endothelial surface
- ENDOTHELIAL production of tissue factor pathway inhibitor (TFPI)
- Inhibits factor Xa : important in clotting
- Plasma levels increased by heparin
Clear Emphasis on endothelial as this is where they all originate.
Describe the role of platelets.
They provide the scaffold required for building the enzyme complexes necessary for generating the fibrous clot of the secondary haemostatic process. Once activated, they release mediators that drive haemostasis forwards. These cause responses such as vasoconstriction, platelet aggregation and vascular repair. They express proteins on the cell membrane that are necessary for platelets to adhere to each other so that the platelet plug can be formed. Before being activated, platelets are small and rounded. Once activated, they transform to protect pseudopodia that help entangle other platelets and aid their aggregation.
what are clotting factors and anticoagulants ?
- Clotting factors: molecules that stimulate its formation
2. Anticoagulants : molecules that inhibit their formation or disrupt clots
what occurs once factor x is activated during extrinsic pathway ?
Again the target of the extrinsic pathway is activation of factor X. Once factor X is activated, it in turn generates thrombin (factor 2a) from prothrombin. Thrombin turns fibrinogen, which is a soluble protein, into fibrin that forms a large matrix of insoluble fibrin that makes up the structure of a clot. Fibrin is colourless and the red colour associated with clots is due to trapped erythrocytes.
what is the simplified process of vasoconstriction ?
The ‘damaged’ blood vessels contract in order to reduce blood flow. they know to contract due to:
- Cells around the damaged area send signals
- Nerve reflexes cause contraction too
- Myogenic spasm also causes contraction
Why don’t platelets bond to healthy cells ?
The healthy cells secrete Nitric oxide & Prostaglandins
These prevent platelet adhesion in non injured areas.
What Is the process of coagulation?
INTRINSIC and EXTRINSIC pathway (clotting factors) lead to prothrombinase
Prothrombinase and Ca2+ catalyse prothrombin to thrombin
Thrombin and Ca2+ acts as an enzyme converting fibrinogen(soluble in blood) to fibrin (insoluble)
Fibrin then crosslinks forming a fibrin mesh which holds the platelet plug in place aswell as slowing the blood flow down.
