haemostasis Flashcards
why clot?
Keep blood in and keeps pathogens out
why localised? where does it happen?
Blood loss is stopped by formation of a plug composed of platelets and fibrin
Tightly regulated process that stops bleeding at the site of an injury
it is localised to prevent unwanted systemic clotting
What trigger the clotting process?
what does endothelium normally maintain?
Endothelium in blood vessels normally maintains an anticoagulant surface
Injury exposes collagen to come into contact with blood components to activate clotting
Two main processes of haemostasis – primary and secondary
What is primary haemostasis?
what do platelets do? (3)
platelet aggregation and platelet plug formation
Platelets:
Adhere
Activate
Aggregate (via fibrinogen)
what is Secondary haemostasis
what is thrombin?
deposition of insoluble
fibrin generated by the coagulation cascade
Thrombin (protease):
Cleaves circulating soluble fibrinogen into an insoluble fibrin mesh
primary and secondary haemostasis
Primary and secondary steps are intertwined at many points. Not really separate processes
primary haemostasis
platelet adherence
what does the endothelium continously release? where is some of this stored too?
what happens if collagen is exposed to blood?
how and why do platelets get activated? what do activated platelets express and what are they required for?
❶The endothelium continuously releases small amounts of von Willebrand Factor, which circulates in the blood. Endothelial cells also store von Willebrand Factor in Weibel-Palade bodies for release when appropriately stimulated.
❷If collagen becomes exposed to blood (because the endothelium is damaged), von Willebrand Factor binds to it.
❸Platelets express receptors for both collagen and von Willebrand Factor and become activated when these proteins bind to them. Activated platelets express functional fibrinogen receptors, which are required for aggregation
primary haemostasis
Platelet activation
Once activated, what do they do? at the same time as this, what do they release (2)? what do these molecules do?
❶ Once activated, platelets begin to aggregate by binding to fibrinogen, which links them together. At the same time, platelets release multiple pro-activation/aggregation signalling molecules such as adenosine diphosphate (ADP) and thromboxane A2 (TXA2).
primary haemostasis
Platelet aggregation - why does this occur? has it seen the wound?
This platelet hasn’t seen the wound. It’s been activated by other platelets. More platelets will follow.
what is the trigger for the coagulation cascade?
effect of this?
Secondary haemostasis
Tissue factor is the sub-endothelial trigger for the coagulation cascade
(tissue factor becomes exposed when endothelial layer is damaged which leads fibronogen to become fibrin)
Amplification: each activated factor activates more of the next
what activates the coagulation cascade? what expresses this? what binds to this and what conversion does it lead to?
how does this lead to the amplification effect?
❷ Tissue factor (TF), expressed by nearly all sub-endothelial cells activates the coagulation cascade to initiate a minor burst of haemostasis. Factor FVIIa binds to Tissue Factor, which ultimately leads to conversion of prothrombin to thrombin
❸. Thrombin activates receptors on platelets as well as the endothelium, amplifying platelet aggregation and initiating release of stored von Willebrand Factor from endothelial cells.
What does thombin activate?
which 2 cofactors does it activate? what do they form and on what?
what do these complexes do? via what?
what are the both specific complexes?
what is this stage called?
Thrombin activates two cofactors, Factor VIIIa ❶ and Factor Va ❷ which subsequently form calcium ion-dependent complexes on the surface of platelets with Factor Xa (AKA the prothrombinase complex) and Factor IXa (AKA the tenase complex).
These complexes greatly accelerate production of Factor Xa and thrombin, respectively. This is the amplification stage of the coagulation cascade. The greatly increased production of thrombin via tenase and prothrombinase contributes considerably more to the process.
(FIXa with FVIIIa and FXa and FVa)
Although there is probably some fibrin formation during the initial activation of thrombin via the TF pathway, the greatly increased production of thrombin via tenase and prothrombinase contributes considerably more to the process. Fibrin formation is
often termed secondary homeostasis.
fibrinolysis
what activiates plasmin? from what?
what does this do?
t-PA = tissue plasminogen activator. Activates plasmin from plasminogen.
Plasmin breaks down fibrin
Thrombin activates two important cofactors, FV and FVIII
what makes both complexes? what do they both do?
what is this combined process responsible for?
The tenase complex: FVIIIa+FIXa to rapidly generate FXa
The prothrombinase complex: FVa+FXa to rapidly generate active thrombin
The subsequent explosive production of thrombin is responsible for the
formation of the insoluble fibrin mesh that holds a blood clot together.
What can go wrong?
3 issues?
Haemophilia - failing to clot (Mutations in coagulation factors)
Thrombosis – clotting in the wrong place which leads to
Arterial (e.g stroke) and venous (e.g. DVT)
Disseminated intravascular coagulation (DIC) – whole body clots -> As in sepsis (body’s response to an infection injures its own tissues and organs) hence Depletion of clotting factors and platelets leads to bleeding
