Blood coagulation: clot formation Flashcards
blood coagulation
transformation of blood into a solid gel called a clot or thrombus
what does a clot consist of
mainly of protein polymer fibrin
where does clotting occur?
locally around platelet plug
function of clotting
support and reinforce platelet plug, solidify remaining blood
what occurs at each step of the coagulation cascade?
inactive plasma protein (factor) is converted to a proteolytic enzyme
proteolytic enzyme catalyses the generation of the next enzyme in the sequence
each activation results from splitting of small peptide fragment from the inactive plasma protein precursor - exposes active site of the enzyme
what does the cascade of plasma enzyme activations require?
activated platelets, plasma cofactors, calcium ions
prothrombin -> thrombin
thrombin catalyses the reaction where several polypeptides are split from molecules of fibrinogen
fibrinogen remnants
bind together to form fibrin
structure of fibrin
loose mesh of interlacing strands
rapidly stabilised and strengthened by covalent cross-linkages mediated by factor XIIIa enzyme
factor XIIIa
formed from factor XIII - reaction catalysed by thrombin
thrombin functions
catalyses the formation of loose fibrin
activates factor XIII
positive feedback on its own function: activates cascade proteins and platelets
what substances are trapped in the fibrin meshwork?
erythrocytes, other cells
when can clotting occur?
in absense of all other substances except platelets
why are platelets necessary for clotting?
several cascade reactions take place on surface of platelets
what do activated platelets display?
specific plasma membrane receptors that bind clotting factors and allow reactions to happen on their surface platelet factor (PF) - phospholipid. cofactor in steps mediated by bound clotting factors
Ca2+ and clotting
required in several steps.
concentration can never decrease enough to cause clotting defects, as death from muscle paralysis or cardiac arrythmias would occur
2 pathways in coagulation cascade
intrinsic - everything it needs is in the blood
extrinsic - cellular element outside of blood is needed
first plasma protein in intrinsic pathway and its contact activation
factor XII
activated to factor XIIa when contacting substances e.g collagen fibres
requires plasma proteins
factor XIIa function
catalyses activation of XI to XIa
factor XIa function
catalyses activation of IX to factor IXa
factor IXa function
activates X to factor Xa
also mediated by factor VIIIa (cofactor, not enzyme)
factor Xa function
enzyme that converts prothrombin to thrombin
haemophilia and factors
excessive bleeding
usually due to genetic absence of factor VIII
sometimes due to absence of factor IX
what does extrinsic pathway begin with?
protein called: tissue factor - not plasma protein
found on outer plasma membrane of various tissue cells, including fibroblasts and cells in walls of vessels outside endothelium
tissue factor function
binds plasma protein - factor VII - activated to factor VIIa
factor VIIa functions
catalyses activation of factor X to Xa and IX to IXa (more factor X via intrinsic pathway)
merging of intrinsic and extrinsic pathways
merge at factor Xa - catalyses conversion of prothrombin to thrombin - catalyses formation of fibrin
thrombin and factors
activationof XI and VIII in intrinsic pathwat, V.
use and importance of intrinsic vs extrinsic factors
extrinsic pathway initiates clotting
factor XII plays little role
amount of thrombin generated by extrinsic pathway is too small to to produce adequate, sustained coagulation
extrinsic pathway triggers thrombin’s positive feedback mechanisms on the intrinsic pathway - activation of factors V, VIII and XI and platelets
-triggers intrinsic pathway w/out XII
thrombin recruits intrinsic pathway and facilitates prothrombin-thrombin step by activating factor V and platelets
official designations for clotting factors and synonyms more commonly used
Factor I (fibrinogen) Factor Ia (fibrin) Factor II (prothrombin) Factor IIa (thrombin) Factor III (tissue factor, tissue thromboplastin) Factor IV (Ca2+) Factors V, VII, VIII, IX, X, XI, XII, XIII (inactive forms of factors) platelet factor (PF)
liver’s role in coagulation cascade
liver disease - bleeding problems
produces many plasma clotting factors
produces bile salts, important for normal intestinal absorption of vitamin K
liver requires vitamin K to produce prothrombin and other factors
