Haemostasis - Coagulation Flashcards
what is VIRCHOW’S TRIAD?
the explanation for pathological thrombus formation
what is Virchow’s triad made up of which helps result in pathological thrombus formation?
Endothelial injury/dysfunction
Stasis of blood flow in veins
Change in coagulability of the blood
blood clotting is highly conserved in all ?
in all vertebrates
change in composition of blood clotting overtime?
very little change over time
positive of blood clotting being similar in humans and animals?
advances in human medicine advances veterinary medicine
coagulation factors are identified by?
by roman numerals
give an example of nomenclature for coagulation factors?
coagulation factors are labelled as ‘F’
so factor 8 is… FVIII
some factors are referred to by name instead - nomenclature
give examples of these factors:
Tissue factor (TF) = FIII = thromboplastin Promothrombin (PT) = FII
Thrombin = FIIa
FVIII refers to a?
a zymogen - inactive precursor (aka prefactor)
zymogen?
an inactive substance which is converted into an enzyme when activated by another enzyme
however, whilst FVIII refers to a zymogen, what refers to an active form of the enzyme?
the inactive form has a lower case ‘a’ after name e.g. FVIIIa
what is the nomenclature for the inhibited (deactivated) forms of the coagulation factors?
they have a lower case ‘i’
e.g. FVIIIai
coagulation are mostly what type of enzyme?
mostly proteases
specifically what type of proteases are coagulation factors?
specifically serine proteases of the chymotrypsin super family
coagulation factors circulate as what?
circulate as zymogens
what are coagulation factors activated by?
activated by proteolysis
for maximal activity, what do coagulation factors require?
cofactors
where are the cofactors, that assist the coagulation factors, found?
these also circulate in plasma in pro-cofactors that are also activated by cleavage
where does the complex of coagulation factors, cofactors and pro-factors assemble?
assemble on negatively charged phospholipid surfaces on platelets
where are clotting factors mainly synthesised and how do they circulate?
in the liver and they circulate in their inactive form
what type of enzyme are most clotting factors?
most are serine proteases except TF, FV, FVIII (all glycoproteins) and FXIII (transglutaminase)
vitamin k?
fat soluble vitamin found in leafy greens
vitamin k is an essential factor for what clotting factor?
for gamma-glutamyl carboxylase which adds a carboxyl group to glutamic acid (Ga) residues on FII, FVII, FIX and FX
what regenerates vitamin K?
regenerated by VKOR (Vit K epoxide reductase)
VKOR is a target of what drug?
warfarin
what does Tissue factor (FIII) trigger?
it is the trigger of blood coagulation (extrinsic pathway) is expressed on surface of cells not ordinarily in contact with the blood - this is termed the Haemostatic envelope
What is the Haemostatic envelope?
it is formed by tissue factor synthesised in the smooth muscle and pericytes of small vessels
what do endothelial cells present and how do they do this?
they present an anticoagulant surface by expression of cell surface by expression of cell surface anticoagulant proteins
give the four cell surface anticoagulant proteins that are expressed by endothelial cells during the resting state?
Thrombomodulin (TM)
Tissue factor pathway inhibitor (TFPI)
Antithrombin
Heparin sulphate proteoglycans
describe the initiation of the procoagulant response: in 4 steps
vascular damage exposes liquid blood to cells expressing TF (tissue factor)
TF associates w/ blood FVIIa and this TF:FVIIa complex activates FIX (to FIXa) and FX (to FXa) - EXTRINSIC PATHWAY
FXa coverts prothrombin to thrombin - COMMON PATHWAY
Thrombin cleaves (soluble) fibrinogen to (insoluble) fibrin to promote clot stabilisation
what does the amplification network cause - during the initiation of the procoagulant response?
it causes explosive thrombin generation (RAPID)
what does thrombin activate?
activates platelets and activated platelets drive thrombin generation on procoagulant surface
what is the central feature that enables the coagulation process to be balanced delicately?
conversion of fibrinogen to fibrin
what do cofactors circulate as?
circulate as inactive forms and they are activated by thrombin
in order to be effective, what needs to happen to FIXa and FXa?
they require assembly into complexes with non-enzymatic cofactors e.g. FVa and FVIIIa (role in haemophilia)
back activation of the cofactors (needed for the procoagulant response) occurs when?
occurs from trace amounts of thrombin made in the initiation phase of the procoagulant response
cofactor activation supports what in the initiation of the procoagulant response?
supports the explosive burst of thrombin generation (referred to as Tenase because of role in making more FX)
FIXa and FX complexes form complexes with non-enzymatic cofactors - these complexes also assemble where?
on phospholipid or fibrin clot surfaces
