Blood coagulation: a puzzle for biologists, a maze for mathematicians - Modeling of Physiological Flows - page 55

Disseminated Intravascular Coagulation (DIC) is a serious pathological condition
leading to the formation of clouds of microthrombi in the bloodstream. A mathemati-
cal model of DIC will be illustrated in Sect. 3.4.2.
FXII deficiency
It produces no significant symptoms and is usually discovered incidentally during
clinical tests, since it causes some retardation of coagulation. In this way it was
first diagnosed in 1955 by O. Rotter in a man called John Hageman (FXII, so far not
mentioned in our review, is also called Hageman Factor ). The paper [73] provides an
interesting historical review of the early works on this subject. We list this disorder in
the last place precisely because it provides a link with the next section. Indeed, FXII
was believed to be the initiator of the so called intrinsic pathway of the Cascade
model. FXII has arisen new interest in different contexts. We will return to it in
Sect. 3.3.3 and 3.4.2.
3.3.2 The limitations of the 3-pathway Cascade model
It is now time to consider the 3-pathway Cascade model, based on the intrinsic,
extrinsic and common pathways.
Intrinsic pathway
So called because it begins within the blood. It starts with the (slow) conversion
of FXII to FXIIa, attributed to a platelet product (HMWK, High Molecular Weight
Kininogen ). FXII activation is then accelerated, since FXIIa converts Prekallikrein
to Kallikrein (proteins which missed to receive a Factor number), which is a fast
activator of FXII. The target of FXIIa is FXI, activated to FXIa, which we already
know to produce the transition of FIX to FIXa. The next step is the activation of FVIII
and the consequent production of tenase, in turn generating FXa with the help of
Calcium ion. From now on the intrinsic pathway merges with the extrinsic pathway.
See also Sect. 3.3.3.
Extrinsic pathway
This simply consists in the combination of FVIIa with TF, which eventually leads
to FXa production.
Common pathway
It basically follows the scheme of the Propagation Phase described for the cell-based
model.
Remark 4. In the Cascade model the intrinsic and the extrinsic pathways can be ini-
tiated independently from each other.
Despite the strict analogies, the Cascade and the cell-based models have two funda-
mental differences.