Biomedical Engineering Reference
In-Depth Information
is seen with some delay. For this reason heparin (see next section) is simultane-
ously administered. Drugs neutralizing vitamin K are on the market with various
trademarks. The most known are Wa r f a r i n (in the USA) 33 and Coumadin .
Activated factors have their own inhibitors , that will be described below
(Sect. 7.3.5 ).
5. Complexes
The following Factor Complexes have an important role in the coagulation pro-
cess:
Complex FVIII-vWF is the main carrier of inactive FVIII in blood. 34
Under the
action of FIIa it dissociates and FVIII is rapidly activated.
Complexes FVII-TF, FVIIa-TF intervene in the initiation phase of the cascade.
Complex FVIIIa-FIXa (CCa CC ) is called Tenase 35
because it activates FX.
Complex FVa-FXa (CCa CC ) is called Prothrombinase because it promotes the
transition from FII to FIIa. We will discuss its pivotal role in the cascade.
Complex Thrombin-Thrombomodulin . Thrombomodulin is a protein expressed
by endothelial cells. This complex induces the activation of Protein C and turns
TAFI (see Sect. 7.3.4 ) into its active form, providing protection to Fibrin.
6. More Coagulation Factors
According to the Cell-Based Model (Sect. 7.4 ), all the Factors listed above enter
the chemical cascade leading to Fibrin production, except FXII.Thisisthemain
discrepancy with the 3-pathway Cascade Model (Sect. 7.6 ), used until recently. In
the latter, activation of FXII is the triggering event of the intrinsic pathway of
coagulation (i.e., a process originated within blood, independently of exposure to
TF, which is of extrinsic nature). Since there is evidence of clotting of intrinsic
origin, and also of the fact that FXII can become activated when blood comes into
contact with artificial materials, the intrinsic pathway, though not endorsed in the
Cell-based Model, still is worth being considered. It is also called contact activation
pathway . Here we list the Factors which, in addition to FXII, take part in it.
Prekallikrein (PK), also known as Fletcher Factor , 36 complexes with High
Molecular Weight Kininogen (HMWK) by contact with collagen, in the presence
of FXII.
33 Patented in 1948 as a rat poison and used as anticoagulant for humans since 1954. It was isolated
in 1941 by a group at the University of Wisconsin after a 6-year work investigating a widespread
hemorrhagic disease that affected cattle in the USA, the so-called sweet clover disease (the research
was funded by WARF, i.e., Wisconsin Alumni Research Foundation). See [ 248 ].
34 Already in the 1950 it was known that deficiency of vWF was accompanied by a deficiency of
FVIII (see [ 208 ]).
35 The symbol X-ase is sometimes used.
36 Also referred to as Williams Factor or Flaujeac Factor .
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