CVS haemostasis Flashcards
What occurs following a vascular injury?
-Following vascular injury, a tightly regulated process stops bleeding at the site of injury and prevent pathogens from entering
What is blood loss stopped by the formation of?
-Blood loss is stopped by formation of a plug composed of platelets and fibrin
Why must a clot remain localised?
-It must remain localised in order to prevent thrombosis
What does the endothelium in blood vessels maintain?
-endothelium in blood vessels normally maintain an anticoagulant surface
What does injury to normal blood vessels do? (Basic outline)
-Platelets and fibrinogen circulate in the blood, ready to go
-Damage to vessel wall will trigger clotting
-Injury exposes collagen to come into contact with blood components to activate clotting
-Results in aggregated platelets and a fibrin mesh
What occurs in primary haemostasis (brief outline)?
Primary haemostasis (platelet aggregation and platelet plug formation)
-Platelets will adhere, activate and aggregate via fibrinogen (triple a’s)
What occurs in secondary haemostasis (brief outline)?
Secondary haemostasis: Deposition of insoluble fibrin generate by the coagulation cascade
-Thrombin enzyme cleaves circulating soluble fibrinogen into an insoluble fibrin mesh
Is primary and secondary haemostasis a separate process?
Primary and secondary steps are intertwined at many points and is not really a separate process
Steps involved in primary haemostasis
- Platelet adherence
-constitutive release of von-willebrand factors(vWF) from endothelium which circulates in the blood
-Endothelial cells also store vWF in wiebel palade bodies for release when stimulated
-If collagen becomes exposed to blood, due to the endothelium being damaged, vWF will bind to it
-Platelets express receptors for both collagen and vWF and become activated when these protein bind to them - platelet activation
- Activated platelets express functional fibrinogen receptors which are required for aggregation via. fibrinogen
-Once platelets are 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 ADP and thromboxane A2(TXA2) (activate and recruit more platelets) - Platelet aggregation
-More platelets will follow and bind using fibrinogen
Steps involved in secondary haemostasis
-Tissue factor is the sub-endothelial trigger for the coagulation cascade
-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, (then to FXa) which ultimately leads to conversion of prothrombin to thrombin
AMPLIFICATION:
-Thrombin activates receptors on platelets as well as the endothelium, amplifying platelet aggregation and initiating release of stored vWF from weibel-palade bodies in endothelium. thrombin releases more vWF hence more thrombin activation in a positive feedback mechanism (maximise conversion of fibrinogen to fibrin)
-Thrombin activates 2 co-factors, factor VIIIa and factor Va which subsequently form calcium ion-dependent complexes on the surface of platelets with factor Xa(also known as the prothrombinase complex) and factor Ixa (also known as 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 complexes contributes considerably more to the process.
-Secondary haemostasis is associated with the propagation of the clotting process via the intrinsic and extrinsic coagulation cascades
How does fibrinolysis occur?
-Tissue plasminogen activator activates plasmin from plasminogen. Plasmin breaks down fibrin into fragments incl. D-dimer
What is thrombosis?
-Clotting in the wrong place
What does arterial and venous thrombosis cause?
-Arterial thrombosis can cause a stroke, MI; venous thrombosis can cause DVT
What does haemophilia cause and what is this due to?
-Causes failure to clot due to mutations in coagulation factors of the tenase complex (FIXa complex)
-Haemophilia A: FVIIIa
-Haemophilia B: FIXa
What is Disseminated intravascular coagulation(DIC) and when does it occur?
Disseminated intravascular coagulation (DIC) -whole bloody clots (systemic clotting)
-As in sepsis (bodys response to an infection injures its own tissues and organs)
-this can simultaneously deplete platelets and clotting factors leading to bleeding
