Circulation 1: Physiological Thrombosis and clotting Flashcards
Describe the origin of platelets.
Platelets are formed by the fragmentation of megakaryocytes, in the bone marrow.
Megakaryocytes can undergo nuclear division and grow very large in the bone marrow. They produce platelets that then bud off from the cytoplasmic extensions of megakaryocytes.
They sit over the sinusoids and deposit the platelets there - which then enter the circulation.
Describe the role of platelets in the formation of a thrombus (in relation to trauma or tissue damage)
When there is a defect in the vessel, blood will escape to the surrounding tissue.
This ultimately results in the exposure of platelets to the interstitial collagen - resulting in the activation of platelets, causing them to aggregate and stick together.
The platelets then adhere to the damage caused by the defect and form a bridge to close the gap.
This process is enhanced by Von Willebrand factor.
Explain the main site of production of key clotting factors.
Mainly produced in the liver (some in endothelial cells).
** some people with chronic liver disease are predisposed to bleeding, due to lack of clotting factors.
Describe the intrinsic mechanism of action of key clotting factors in the formation of fibrin (from fibrinogen) in producing clots and thrombi.
The clotting cascade is an amplification system, (the intrinsic pathway is slightly slower).
Damage to the vessel causes contact with the sub-endothelial tissue, there is then a cascade of many different clotting factors (along with the continual positive feedback of thrombin into the pathway).
An Xa-Va complex reacts with prothrombin = thrombin, which reacts with fibrinogen to give fibrin.
Cross-linked fibrin is the end product from an additional input from thrombin to a clotting factor- then to fibrin = cross-linked fibrin.
Describe the extrinsic mechanism of key clotting factors in the formation of fibrin (from fibrinogen) in producing clots and thrombi.
This is a direct response to damage, and is described as a burst of thrombin formation.
The damage recruits Tissue Factor which combines with clotting factor, VII to create the complex TF-VIIa - this complex reacts with other clotting factors that then feed into prothrombin to produce thrombin, and so on and so forth.
Describe the overall mechanism and design of the coagulation cascade.
The cascade is designed to keep the clotting factors inactive until they come into contact with an activator (e.g. contact with the sub-endothelial tissue).
Activation allows them to then interact with their cofactor.
Cofactor + factor = Active complex, this process carries on all the way down.
Describe coagulation, in the form of a clot.
Obviously originates from a defect in the vessel, from which the blood rushes out of the vessel and becomes stagnant.
Within the stagnant blood, next to the interstitial collagen, the clotting cascade is activated.
A clot consists of a network of fibrin strands and RBC’s.
The clot serves to fill up the space in the dermis, however this may not work and the defect may continue to bleed.
Describe coagulation, in the form of a thrombus.
Thrombosis occurs in flowing blood only.
A pure thrombus is pale cream coloured, and is composed of platelets and fibrin strands.
Platelets have molecules on their surfaces which allow them to adhere to the interstitial collagen (even when blood is flowing).
From here, the clotting cascade deposits Factor VII which enhances this more.
Describe the main difference between a thrombus and a clot.
Clots occur in stagnant blood, and thrombi occur in flowing blood.
Clots have NO white blood cells, (thrombi have platelets).
Describe the aftermath of coagulation from trauma to the vessel or tissue damage.
Granulation tissue (aka the “universal patch”) is vital in this process.
Granulation tissue formation is possible from the activity of fibroblast cells and from the production of vascular endothelial growth factors.
The fibroblasts are responsible for producing mature fibrous tissue, and the blood vessels aid in oxygenating the area of wound to keep it alive.
Describe process of Thrombolysis.
The thrombus must be removed, if not, the consequences are fatal (e.g. pulmonary embolism or tissue ischemia).
A plasma protein plasminogen converts to plasmin (by the production of tissue plasminogen activator - as a result of the clotting cascade).
Plasmin can then cut up the Fibrin into smaller fragments (fibrinolysis) as a way of removing it.
