Biomedical Engineering Reference
In-Depth Information
damage, thus forming a clot (thrombus) to seal it off. These mechanisms are effective in dealing
with small vessel injuries (e.g. capillaries and arterioles), although they are ineffective when the
damage relates to large veins/arteries.
12.2.1 The coagulation pathway
The process of blood coagulation is dependent upon a large number of blood clotting factors,
which act in a sequential manner. At least 12 distinct factors participate in the coagulation cas-
cade, along with several macromolecular cofactors. The clotting factors are all designated by Ro-
man numerals (Table 12.1) and, with the exception of factor IV, all are proteins. Most factors are
proteolytic zymogens, which become sequentially activated. An activated factor is indicated by
inclusion of a subscript 'a' (e.g. factor XIIa is activated factor XII).
Although the fi nal steps of the blood clotting cascade are identical, the initial steps can occur
via two distinct pathways: extrinsic and intrinsic. Both pathways are initiated when specifi c clot-
ting proteins make contact with specifi c surface molecules exposed only upon damage to a blood
vessel. Clotting occurs much more rapidly when initiated via the extrinsic pathway.
Two coagulation factors function uniquely in the extrinsic pathway: factor III (tissue factor) and
factor VII. Tissue factor is an integral membrane protein present in a wide variety of tissue types
(particularly lung and brain). This protein is exposed to blood constituents only upon rupture of
Table 12.1
The coagulation factors that promote the blood clotting process. Note that the factor originally
designated as VI was later shown to be factor Va
Factor
number
Pathway in which
it functions
Common name
Function
I
Fibrinogen
Both
Forms structural basis of clot after its conversion to fi brin
II
Prothrombin
Both
Precursor of thrombin, which activates factors I, V, VII,
VIII and XIII
III
Tissue factor
(thromboplastin)
Extrinsic
Accessory tissue protein which initiates extrinsic
pathway
IV
Calcium ions
Both
Required for activation of factor XIII and stabilizes some
factors
V
Proaccelerin
Both
Accessory protein, enhances rate of activation of X
VII
Proconvertin
Extrinsic
Precursor of convertin (VIIa) which activates X (extrinsic
system)
VIII
Antihaemophilic
factor
Intrinsic
Accessory protein, enhances activation of X (intrinsic
system)
IX
Christmas factor
Intrinsic
Activated IX directly activates X (intrinsic system)
X
Stuart factor
Both
Activated form (Xa) converts prothrombin to thrombin
XI
Plasma
thromboplastin
antecedent
Intrinsic
Activated form (XIa) serves to activate IX
XII
Hageman factor
Intrinsic
Activated by surface contact or the kallikrenin system.
XIIa helps initiate intrinsic system
XIII
Fibrin-stabilizing
factor
Both
Activated form cross-links fi brin, forming a hard clot
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