Haemostasis Flashcards
What two factors are necessary to maintain the circulation of blood in fluid state to blood vessels?
Fibrinolytic anticoagulant proteins
Coagulation factors, platelets
Describe the structure of platelets
Discoid
Non-nucleated
Contain granules (alpha and dense)
Where and how are platelets formed?
Bone marrow
Fragmentation of megakaryocytic cytoplasm from myeloid stem cells
Describe the vasoconstriction stage of haemostasis
Nitric oxide and prostacyclin levels are lower than endothelin. Vasoconstriction occurs to lower blood loss.
Outline the process of Platelet adhesion during primary haemostasis
Platelets can bind directly or indirectly to the endothelium.
How do platelets bind to the endothelium (directly)
When endothelial cells are lost, collagen is exposed.
GP1a receptors on the platelet bind to the exposed collagen, activating the platelet.
How do platelets bind to the endothelium (indirectly)
Von Willebrand Factor is produced by damaged endothelial cells. The platelets bind to the VWF through the GP1b receptor. VWF binds to the collagen on endothelium
What do the alpha granules contain?
Von Willebrand Factor
Fibrinogen
What do dense granules contain?
ADP
Ca 2+
Serotonin
How does the activation and degranulation of platelets occur in primary haemostasis?
Platelet and GP1b receptor changes shape so that it can bind to the endothelium.
Alpha and dense granules released from platelets.
Platelets are activated by the ADP causing conformational change in the GPIIb/IIIa receptor to bind to fibrinogen.
How is Thromboxane A2 synthesis stimulated?
Through the activation of platelets.
Platelets produce prostaglandin thromboxane A2 from arachidonic acid from cell membrane
Describe the final step of platelet aggregation in primary haemostasis
Release of ADP and Thromboxane A2 from platelets.
They bind to receptors on the platelets to encourage recruitment, adhesion and aggregation of platelets to form an unstable platelet plug.
What does Prostacyclin do?
prostacyclin is a vasodilator (from endothelial cells). It suppresses platelet activation- prevents inappropriate platelet aggregation (elevates cyclic AMP levels)
How does aspirin inhibit activation of platelets?
Inhibits the production of thromboxane A2 by irreversibly blocking the action of Cyclo-oxygenase enzyme (COX). This reduces platelet aggregation
How does Clopidogrel work?
Clopidogrel irreversibly blocks P2Y12 receptor so that ADP cannot bind to platelets.
What is the function of Fibrin?
Stabilises the platelet plug and stops blood loss for the blood vessel to be repaired.
What happens in the initiation stage of Secondary Haemostasis
TF is exposed on the endothelium.
TF causes 7->7a
causes X->Xa
leads to activation of prothrombin (F2->2a) to small amount of thrombin
What happens in the amplification stage of Secondary Haemostasis
Small amount of thrombin from initiation phase activates cofactors V and VIII
Zymogen factor XI platelets
Outline the propagation stage of haemostasis
Factor XI converts:
- Factor IX to IXa
-Factor X to Xa (with factor VIII)
-leads to rapid burst in thrombin generation
What is the function of Proteins C and S?
Protein C is activated when thrombin binds to thrombomodulin on the endothelial cell surface.
Activated protein C will inactivate factors Va and VIIIa in the presence of Protein S.
How does antithrombin promote anticoagulation
Thrombin and Factor Xa inactivated by circulating inhibitor antithrombin.
How does heparin promote anticoagulation?
Heparin enhances the binding capabilities of antithrombin to factor II (prothrombin)
How do heparin and antithrombin work together to promote anticoagulation?
Larger chains of heparin are needed to wrap around the antithrombin and thrombin to inactivate thrombin.
How does warfarin act as an anticoagulant?
Warfarin is a Vitamin K antagonist (interferes with protein carboxylation)
Reduces synthesis of factors II, VII, IX, X by the liver
