Haemostasis + Platelets Flashcards
What is haemostasis
Arrest of bleeding from blood vessels and sealing them
What is formation of cell fragment platelets from megakaryocytes regulated by
Thrombopoietin in liver and kidney
Explain the steps of thrombopoiesis
Haematopoietic sc turns to common myeloid progenitor
This produces a megakaryoblast
Repeated mitosis of megakaryoblast turns to a megakaryocyte
This extends arms through the bone marrow sinusoid (stimulated by thrombopoietin)
These arms break off as platelets
Where are platelets stored and secreted and phagocytosed when dying
Stored in spleen and secreted down the sympathetic NS
Phagocytosed by liver and spleen
What are the 7 components of platelets
1- cell membrane 2- exterior coat 3- tubular system 4- microtubules 5- granules 6- delta bodies 7- mitochondria
What is importance of exterior coat in platelets
Glycoprotiens
For adhesion, agreggation and activation in haemostasis
What does the tubular system produce
Thromboxane A2
What do granules alpha do
Form clotting mediators like Von Willebrand , VIII and fibrinogen
What do delta bodies contain
Adp, ca2+, serotonin (for clotting)
What are the 3 stages of haemostasis
1- vascular spasm(contraction)
2- formation of platelet plug
3- blood coagulation
What happens in the vascular spasm
When there is damage in the vessel VASOCONSTRICTORS LIKE SEROTONIN AND ADH construct muscle layer to stop blood flow out
The endothelial layers between cut adhere together when contracted
This sticking is aided by platelets which are exposed to collagen
Why is collagen important in the adhesion of endothelial cells by platelets
They activate them and also attract more platelets to it
Explain platelet plug formation
Platelets adhere via the help of exterior coat and collagen
Stuck in cell wall which uses VON WILLEBRAND FACTOR
They become activated when form a plug and this causes further vasoconstriction and stimulates coagulation
What do normal vessels release to stop aggregation of platelets
Prostacyclins
Which molecule in coagulation causes the clot form
Fibrin from fibrinogen
Explain how fibrinogen gets converted to fibrin in the last steps of coagulation
Fibrinogen converted to fibrin monomers first via thrombin IIa
Fibrin monomers form fibrin polymer for clot via factor XIIIa (13) and ca2 from the delta bodies
What activates XIIIa
Thrombin IIa
What are the 2 pathways which come together to stimulate thrombin IIa
Intrinsic
Extrinsic
What stimulates the cascade in the intrinsic pathway
Exposure to collagen and damage of vessel wall
What stimulates extrinsic pathway needed to help intrinsic
Exposes tissue factor IIIa which is released by endothelial cells
How does the extrinsic help activation of factor X which then activated thrombin IIa
Factor IIIa (released by endothelial cells) forms a complex with VII to activation factor X
How does Xa allow production of thrombin IIa
Concerts prothrombin II via ca2+
What are the 2 positive feedbacks in the system of coagulation
1- from thrombin IIa to the intrinsic pathway
2- from Xa to extrinsic pathway
How is antithrombin an anti clotting system
Inhibits factors like thrombin II needed to convert fibrinogen
How is tissue factor pathway inhibitor an anti clotting system
Binds to the IIIa/VII in extrinsic pathway and therefore inactivates Xa
How can thrombin be used as negative feedback
When it binds to its receptors it can stimulate prostaglandins, NO and adp production
This stops platelet aggregation
How is thrombomodulin used as an anti clotting system
Produced by endothelial cells and binds to thrombin IIa and stops its effects
Which 2 proteins are activated by thrombomodulin and stop Va and VIIIa in intrinsic pathway
C and S
What is fibrinolysis
Clot breakdown
Which platelet growth factor recruits fibroblasts and plasmin
Beta
What does fibroblast recruitment by GF b help do
Form scar tissue at damage site
Why is plasmin enzyme important
Fragments fibrin
What molecule activated plasmin from plasminogen
TPA plasminogen activator
Why does TPA only work if clot is present
TPA activated by binding to fibrin which is only present in clotting
What does Von Willebrand do to platelets
Stuck them to the cell wall when activated by collagen to form plug
