Lecture 10 - Physiological Coagulation Flashcards
Thrombin functions?
converts single protein fibrinogen into fibrin molecules that are linked together, activates factors VIII, V, XI, and XIII, activates protein C, inflammation
Concept of enzyme catalytics?
efficient rapid cleavage - much faster than when the cofactor is not there
Tissue factor (VIIa)?
essential for survival, expressed on subendothelial tissue (e.g. muslce) and not on the endothelium itself
Part 1: initiation complex?
TF attracts VIIa, together activating IX and X, X converts small amount of prothrombin (II) into thrombin (IIa), IIa activates VIII and V
Part 2: Complex 2?
VIIIa acts as cofactor to protease IXa activating more X, calcium and phospholipid requirement; factor XI activated by IIa which in turn activates more IX as an amplification loop
Part 3: Complex 3?
Xa with cofactor Va converts a lot more prothrombin into thrombin (IIa), which in turn activates more of VIII, V and IX as an amplification loop
Tissue Factor Pathway Inhibitor?
inhibits factor VIIa (tissue factor) early at process
Protein C and S?
activated by thrombin to inhibit factor VIIIa and Va (S is cofactor)
Antithrombin?
inhibits factor Xa and thrombin, alos IXa and XIa with low efficacy
Common pathway?
Xa and Va activating IIa which activates Ia (fibrin)
Cofactors specific mechanism?
lines proteins up on lipid bilayer so proteins can be efficient
Actions of vitamin K?
cyclic process in liver - carboxylates glutamate residue in GLA region of vitK dependent proteins, necessary for binding of membranes and activity; failure results in bleeding (haemmorhagic disease of the newborn)
Ca2+ function?
folding of carboxylated Gla residues
Contact activation?
XII activating XI which activates IX - important in lab tests but not physiological clotting
Fibrinolysis?
tissue plasminogen factor converts plasminogen into plasmin, plasmin converts fibrinogen into FDPs and fibrin clots into D-dimers - aims to prevent excessive coagulation and breaks down clots
