Blood Clotting Flashcards
What can abnormal clotting cause?
vascular occlusion and infarction
What are the 4 major players of Forming a clot?
1) Endothelial cells
2) Subendothelial tissue
3) Platelets
4) Clotting factors
Describe von Willebrand Factor
mediates platelet adhesion to exposed extracellular matrix when the endothelial lining of blood vessel is damaged, present in plasma and the extracellular matrix; adhered platelets become activated by agents that increase the [Ca2+] of platelets
What happens once von Willebrand Factor is activated?
receptor for fibrinogen becomes exposed on the platelet memebrane, Fibrinogen binds this and causes platelet aggregation
Is fibrin normally found in blood?
no, but its precursor fibrinogen is
Is aggregation of platelets alone enough to seal large wounds?
no
what converts fibrin to fibrinogen
protease thrombin
Describe how protease thrombin works
1) cleaves 2 peptide binds between A(alpha) and B(beta) chains releasing 2 peptides (fibrinopeptides A and B)
2) remaining peptide= fibrin monomer
3) once monomer are formed, they aggregate into fibrous structure
why is fibrinogen more soluble
b/c the fibrinopeptides are covered in negatively charged aspartate and gultamate residues (which repel fibrinogen and prevent aggregation)
Describe Factor XIII
transglutaminase which catalyzes the crosslinking of fibrinogen monomers that form a soft gel instead of a clot
where is thrombin limited to
the site of injury
what produces thrombin
prothrombin by factor Xa
what does the inactive fragment of thrombin contain
10 residues of (gamma)-carboxyglutamate (produced by hepatocytes in rxn requiring vit K)
what is the one protease factor unique to the extrinsic pathway
factor VIIa. active only in the presence of tissue factor(exposed after injury)
What is the Contact Phase Activation
initiating rxns of the intrinsic pathway
what 2 proteases are required for contact phase activation
1) Kallikrein
2) Factor XIIa
also requires HMWK (high molecular weight kininogen)
Describe the steps of the Intrinsic Pathway
Factor XIIa activates Factor XI which activates Factor IX which activates Factor X (this step requires Factor VIIIa)
what is the most important clotting inhibitor
ATIII (others include alpha1-antiprotease and alpha2-macroglobulin)
what activates ATIII
heparin
Describe Thrombomodulin
on the surface of endothelial cells, binds circulating thrombin(which will now not be able to bind to substrates) instead Protein C is activated which degrades factor Va and VIIIa
where is thrombomodulin found and why is this important
only on intact endothelium, this helps prevent clot formation on areas with no endothelial damage
what does Plasmin do
degrade the fibrin clot
what is Plasmin formed from
inactive precursor plasminogen which binds the fibrin clot with high affinity
fibrin complex is activated by what activator
tissue type plasminogen activator (tPA)
