Flashcards in Week 4 HRM Haemostasis Deck (41):
What is the function of Haemostasis?
The way in which the body works to prevent blood from flowing out of blood vessels when they are injured. Involves process of cot formation and then dissolution and tissue repair.
What are the three steps of Haemostasis?
1. Vasoconstriction/vascular spasm
2. Platelet plug formation
What causes vasoconstriction of blood vessels?
1. The direct effect of the trauma has on the endothelium causes the smooth muscle to contract
2. Endothelial cells release endothelin - powerful vasoconstrictor
3. Platelets release thromboxane A2 and serotonin
How are platelets activated?
When they come into contact with damaged blood vessel wall, especially in contact with collagen fibres
What changes occur in a platelet from its inactive to its active form?
Upon coming into contact with a damaged blood vessel, platelets will change shape from smooth membrane to a irregular, spiky shape. Adhere to collagen fibres and VWF to anchor them to the site of injury. Release granules containing thromboxane, serotonin and ADP.
How does the platelet plug form?
The platelet adheres to the injured site via VWF, And the granules it releases causes the activation of other platelets to aggregate and adhere at the site of injury. These all clump together to block off the hole in the blood vessel and prevent blood from leaking.
What prevents platelets from activating when there is no injury, and what prevents them from endlessly aggregating once activated?
Intact endothelial cells release nitric oxide (vasodilator) and prostacyclin which both act to prevent platelets aggregating in undamaged tissues. The same factors restrict the platelet aggregation to the site of injury only.
What is role of ADP released from the platelets?
Enhances platelet aggregation
What is the difference between the primary and secondary Haemostasis?
Primary involves activation by the injury to the blood vessel, the initial response of vasoconstriction and formation of platelet plug.
Secondary Haemostasis involves the coagulation pathways which are delayed and a more prolonged response
What is Von Willebrand Factor and what is its role in Haemostasis?
Plasma protein circulating bound to factor VIII. Binds to collagen fibres in damaged blood vessel walls and anchors platelets to itself, forming a bridge.
What is the role of cAMP in regulating platelet aggregation?
cAMP controls the levels of calcium in the cell which mediate adhesion and aggregation. Prostacyclin released from the endothelial cells are responsible for preventing aggregation in normal conditions by binding to platelets and activating adenylate cyclase and causing high levels of cAMP and therefore low levels of calcium. When this isn't happening, calcium levels increase and thromboxane production and secretion are high and favours aggregation and adhesion.
What is the basic mechanism of blood coagulation?
Activated factors go on to form prothrombin activator complex, which is catalyses the formation of thrombin from prothrombin. Thrombin then acts to form fibrin monomers from fibrinogen
What is the role of vitamin K in coagulation?
Essential for the formation of prothrombin in the liver, along with 4 coagulation factors
How does coagulation work together with the platelet plug?
Coagulation acts to reinforce the platelet plug which as already formed.
Fibrin fibres extend throughout the plug and attach to the damaged walls. The fibres act as a mesh that traps all the blood cells together
What is the initial trigger for the extrinsic pathway?
The release of tissue factor into the blood from damaged tissue. It acts as an enzyme and continues the cascade by activating factor VII
What is the initial trigger for the intrinsic pathway?
Intrinsic means that all the components are within the blood. It is activated when factor XII contacts collagen fibres and it becomes a proteolytic enzyme that continues on the rest of the pathway
What is the role of calcium in coagulation pathways?
It is required for each of the steps apart from the first 2 in each pathway. It is an absolute requirement for successful blood clotting. Incredibly rare for calcium deficiency to be the cause of bleeding disorder.
Where do the two pathways converge to a common pathway?
The activation of factor X to Xa is where the pathways converge. From this point X binds to V and phospholipids to form the prothrombin activator
How can clotting be prevented when blood is taken out of the body?
Either through being placed in a silicon coated test tube, or having citrate or oxalate ions added to bind all the calcium and prevent clotting
What is the other procoagulation function of thrombin?
Thrombin also has a positive feedback effect on factor V to activate it, which accelerates the action of the prothrombin complex
What is the complex 'tenase'?
In the intrinsic pathway it is the tri molecular complex of factor IXa and factor VIIIa combined with calcium and phospholipids to form an enzyme which converts factor X to factor Xa
Why is tissue factor referred to as a receptor for factor VII?
When tissue factor becomes present in the blood, factor VII bind to it and becomes activated. This complex together with calcium activates factor X and is the point where the pathways merge
What is a thrombus?
An intravascular clot
What is a clot composed of?
Mesh network of platelets and fibrin threads saved together, entrapping RBCs and leukocytes
What is the name of the fluid that is squeezed out of the clot during clot retraction?
It doesn't contain the clotting factors
What role does the normal endothelium directly have an anticoagulant effect?
The normal surface repels clotting factors and platelets.
Thrombomodulin a membrane bound protein endothelial layer, binds thrombin (and so prevents the clotting action of thrombin.
Thrombomodulin-thrombin complex activates plasma protein C which is an anticoagulant by inactivating activated factors V and VII
How do the fibrin threads act as anticoagulants?
85-90% of the thrombin formed from the prothrombin is adsorbed to the fibrin fibres they develop, taking away their ability of form more fibrin
What is antithrombin and how does it act?
A plasma protein synthesised in the liver. Binds to thrombin and prevents its coagulation effects.
What part of the coagulation pathway does tissue factor pathway inhibitor act on?
It binds to the tri molecular complex of the extrinsic pathway to prevent the formation of thrombin
How does plasminogen aid in dissolving the clot?
Plasminogen is a freely circulating plasma protein. When a clot forms it contains lots of plasminogen within the network. Days after clot is formed, endothelium secretes tissue plasminogen activator which causes the proteolytic activity of the plasminogen to break down the fibrin.
What cells is heparin mainly found in?
Mast cells and basophils
How does heparin exert an anticoagulant effect?
It binds to antithrombin and activates it. Antithrombin inhibits the activation of important clotting factors, the prothrombin activator and also directly binds thrombin itself.
How does warfarin act to promote anticoagulation?
Inhibits the synthesis of vitamin K, which inhibits the production of vitamin k dependent clotting factors
How does aspirin exert its anticoagulant effect?
Acts on platelets. Inhibits cyclooxygenase enzyme which is needed for platelet aggregation
What is the use of streptokinase?
Converts plasminogen to plasminogen to increase degradation of the clot
What is bleeding time?
Time taken from initial oozing of blood until arrest of bleeding. Involves vasoconstriction and the platelet plug
What is thrombocytopenia?
Abnormally low numbers of platelets in the plasma
What is clotting time?
Time interval from oozing of blood to formation of clot. Usually between 3-10 minutes. Tests intrinsic and common pathway
What disease might an increased clotting time indicate ?
What is prothrombin time?
Time taken for blood to clot after tissue factor and calcium are added. Usually 10-14 secs. Tests the extrinsic and common pathway.