Page 2139 - Hematology_ Basic Principles and Practice ( PDFDrive )

1900 Part XII Hemostasis and Thrombosis

A Initiation C Termination
TF VIIa VIIa TFPI
VIIIa TF Xa VIIIa
X IX X X
IXa IXa
IXa IXa
Xa

Xa Xa Xa Xa = ATIII

Va Va
II II
Xa Xa

IIa IIa = ATIII

B
VIIa TFPI Propagation
TF IIa
Xa VIIIa
X TM C
IXa
IXa

Xa Xa
Va
II APC
Xa
A 2 NA 2 N
A 2 C
C
A 2
Va
IIa APC

Fig. 126.13 REGULATION OF THE DYNAMIC PROCOAGULANT RESPONSE. Initiation (A),
propagation (B), and termination (C) of thrombin generation and the procoagulant response are illustrated.
Four vitamin K–dependent complexes are shown: extrinsic tenase, intrinsic tenase, prothrombinase, and
protein Case. The procoagulant response is regulated by the stoichiometric inhibitors AT and TFPI. AT
inhibits thrombin, factor Xa, and factor IXa that are free in solution. TFPI inhibits both factor Xa and the
factor VIIa–TF–factor Xa complex. APC generated from the protein Case complex (TM–thrombin [IIa])
inactivates factor Va and factor VIIIa by proteolysis of their heavy chains. Low levels of thrombin are required
to initiate clot formation (initiation phase) and trigger the coagulation cascade response (propagation phase).
The enzymes, cofactors, and inhibitors act together to generate a hemostatic response that can be divided into
an initiation phase and a propagation and termination phase. During the initiation phase, factors X and IX
are converted to their respective serine proteases factor Xa and factor IXa; low levels of thrombin are subse-
quently generated by factor Xa. This thrombin then can activate platelets and the procofactors factors V and
VIII, which stimulate further thrombin generation during the propagation phase. Thrombin generation is
attenuated by shutting down the initiation phase by means of the stoichiometric inhibitor of the extrinsic
tenase complex, TFPI, followed by AT, which directly inhibits thrombin and factors Xa and IXa. APC,
Activated protein C; AT, antithrombin; C, protein Case; TF, tissue factor; TFPI, tissue factor pathway inhibi-
tor; TM, thrombomodulin. (From Mann KG: Coagulation explosion, Burlington, Vermont, 1997, Vermont Business
Graphics, with permission.)