41.1 Haemostasis Flashcards
What is a blood clot?
Semisolid mass composed of both platelets and fibrin entrapped in a mesh of fibrin and blood cells
Define haemostasis
Process that prevents excessive blood loss (haemorrhage)
How does a breach of the endothelium lead to platelet adhesion?
Exposes platelet receptors to ligands that are components of the subendothelial matrix: collagen (Ia), fibronectin and laminin (Ic)
How does AT III work?
Binds and inhibits factor Xa and thrombin
How does the endothelial lining of blood vessels prevent thrombosis?
-Physical barrier separating platelets and coagulation factors from stimulatory collagen
-Secretion of heparan sulphate to activate AT II
-Synthesis of inhibitors of platelet activation (prostacyclin, NO)
How does the extrinsic pathway occur if factor VII is inside the vascular system and tissue factor is on non vascular cells?
Injury to endothelium allows for Factor VII to come in contact with tissue factor which non proteolytically activates Factor VII to VIIa
How does thrombomodulin work?
Forms a complex with thrombin and removes it from circulation
How is haemostasis achieved (4)?
-Vasoconstriction
-Increased tissue pressure
-Platlet plug
-Coagulation (clot formation)
List the factors that inhibit clotting
-Blood flow
-TFPI (Tissue factor pathway inhibitor)
-Antithrombin III
-Thrombomdulin
-Activated protein C
-Clot degradation (fibrinolysis)
Other than adhesion, what does binding of platelet receptors to ligands cause?
Causes a conformational change in the receptor that initiates an intracellular signalling cascade leading to PLATELET ACTIVATION
State the intrinsic pathway
What activates the conversion of plasminogen to plasmin?
t-Pa (tissue plasminogen activator) (increased levels of t-Pa by caetcholamines)
What are platelets?
Thrombocytes: small colourless cell fragments of megakaryocytes made in bone marrow
Life spand of 8-10 days
Secrete vasoactive mediators (TXA2, 5-HT)
What are the ‘factors’?
Most are serine proteases- once activated it catalyses a specific proteolytic event in the subsequent factor
What are the three processes that occur when a platlet plug is formed?
-Adhesion
-Activation
-Aggregation
What are the two pathways in the coagulation cascade?
Intrinsic and extrinisic pathway that converge to a common pathway
What causes haemophilia?
Inability to synthesis clotting factors (VIII) (IX)
What causes the cleavage of X to Xa in the extrinsic pathway?
Tissue factor + Ca + Factor VIIa