Biomedical Engineering Reference
In-Depth Information
•
The cell-based model ignores FXII, which in the cascade model can trigger coagu-
lation.
•
The extrinsic pathway bypasses FVIII, making it not strictly necessary. Now two
important experimental features must be taken into account:
a. FXII deficiency (described above) has little effect on coagulation;
b. FVIII deficiency is the cause of hemophilia A, which on the contrary is an
important coagulation related illness.
Differently from the 3-pathway cascade model, the cell-based model is perfectly
compatible with a, b. The above argument does not exclude that some coagulation
can be triggered by FXII activation (we will return to this point in the next section).
The influence of the 3-pathway Cascade model has been so strong that it survives
even in recent topics [16].
3.3.3 Deep Vein Thrombosis (DVT) and coagulation on artificial
surfaces
Having established the concept that blood coagulation is initiated by FVIIa coming
in contact with TF exposed by an injury and following a scenario of shear stress me-
diated platelets-vWF adhesion, it is legitimate to ask how spontaneous thrombi for-
mation can occur in a regime of reduced (or altered) blood flow or blood stagnation.
We are talking about the ill famed “economy class syndrome”, affecting passen-
gers who stay seated for too long time during overseas flights
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. In that case there is
no injury and there is no mechanical stress, therefore such a pathogenic thrombosis
must be initiated within the blood (i.e. has to be
intrinsic
). Atrial fibrillation can also
trigger coagulation increasing the risk of strokes, thus requiring a preventive antico-
agulant treatment. Coagulation on artificial surfaces poses a very similar question,
since endothelium TF is not available. In both cases, if the role of FXII is excluded,
a source of TF must be identified to initiate the process. The explanation of DVT
onset comes from the ability of monocytes to express TF in abnormal conditions.
Apparently, slow flow or stagnation (which in turn produce an abnormal environ-
ment, for instance low oxygen concentration levels) stimulate monocytes to produce
TF. TF production by monocytes is a rather complex process in which other cells are
involved (including platelets). For an explanation see [19]. We also remember that
DVT is greatly facilitated by the tendency of RBCs to aggregate in low shear stress
conditions [80]. In the paper [50] researches on the possible “pathological” deliv-
ery of Tissue Factor from the blood vessel wall are discussed. Coagulation has been
observed to occur on artificial surfaces implanted in patients (e.g. blood pumps).
Essential features of thrombus growth are Thrombin production (without which no
Fibrin would be available) and surface adhesion. Concerning Thrombin, it can be
conjectured that (like in the case of DVT) monocytes are stimulated to produce TF
as a reaction of the immune system to the exposure to artificial material. More dif-
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DVT normally affects legs. It occurs much less frequently in arms. DVT of axillary or subclavian
vein is known as
Paget-Schrotter disease
.
