Biomedical Engineering Reference
In-Depth Information
Complexes in the blood coagulation process
Factors may combine in complexes which have a specific and crucial task in blood
clotting. We have already mentioned the FVIII-vWF complex as the natural source
of FVIII in blood. Let us list other important complexes having an active part in
clotting.
FVIIa-TF: converts more FVII to FVIIa, thus providing more of the same com-
plex; activates FIX, FX.
FVa-FXa ( Prothrombinase ): in the presence of ions Ca2 + it stimulates the key
transition FII
FIIa (Thrombin) .
FVIIIa-FIXa-Ca ++ ( Tenase ): generates FXa very effectively on platelets surface.
Inhibitors of blood coagulation
Clotting is terminated (and prevented when it is not necessary) by the combined
action of some inhibitors:
TFPI ( Tissue Factor Pathway Inhibitor ), secreted by endothelium, blocks the
complex FVIIa-TF and inactivates FXa (by forming a complex with it).
AT-III ( Antithrombin-III ), present in plasma, quenches Thrombin production op-
erating on most of the activated factors, and neutralizes existing Thrombin. Hep-
arin 8
strongly enhances the action of AT-III, thus preventing coagulation.
Protein C (PC): when Thrombin combines with the vascular Thrombomoduline
(TM) it activates PC to APC, which complexes with Protein S and binds to FVa
and FVIIIa, switching off the production of Thrombin. Thus Thrombin is at the
same time the engine and the brake of blood coagulation . Protein Z is also an
inhibitor of FXa.
Remark 1. A very special role in blood coagulation is played by Vitamin K (actually
a group of vitamins) which intervenes in the activation of FII, FVII, FIX, FX and in
the regulation of Proteins C, S, Z (which are said to be vitamin K dependent). The
widely used anticoagulant warfarin 9
inhibits Vitamin K action. 10
3.2.2 Primary hemostasis
Primary hemostasis precedes the main coagulation process and provides a rapid seal-
ing of the wound via platelets adhesion to collagen and to vWF immobilized in the
endothelial tissue exposed to blood. Such a platelet aggregate is sometimes called
a white thrombus (to distinguish it from the blood clot still to be formed, the red
8 Heparin was discovered in 1918 [39]. It also has the side effect of reducing the platelets count
( Heparin Induced Thrombocytopenia , HIT), see e.g. [43], accompanied by an increase of Fibrino-
gen level.
9 Better known in Europe with the trade name Coumadin . Patented in 1948 as a rat poison and used
as anticoagulant for humans since 1954.
10 The very first action of warfarin is to favor clotting, via the inhibition of PC, PS, PZ, while
the antithrombotic effect takes place with some delay. For this reason warfarin is administered in
combination with heparin.
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