Page 70 - Color Atlas Of Pathophysiology (S Silbernagl Et Al, Thieme 2000)

Hemostasis and Its Disorders
2+
The hemostatic system protects the organism – factor IV (Ca )
against bleeding and blood loss. It involves – factors VII–XIII
plasma factors, thrombocytes (platelets), and – prekallikrein ([PKK]; Fletcher factor)
the vessel wall. Their interaction locally guar- – high-molecular kininogen ([HMK];
antees the sealing of leaks in the vessel when Fitzgerald factor)
platelets temporarily “glue” it together (white and the inhibitory factors (→ E):
thrombus), and subsequently the plasma co- – antithrombin III
agulation system forms a firm fibrin tangle – α 2 -macroglobulin
(red thrombus) and thus a stable closure is – α 1 -antitrypsin
formed. However, excessive clot formation – protein C , and
K
(thrombi) with consequent occlusion of larger – protein S K
2+
blood vessels (thrombosis) and the migration With the exception of Ca , they are all globu-
of thrombi (emboli; → p. 240) must be avoided. lar proteins with a molecular mass between
To keep this balance the hemostatic system, 54 kDa (α 1 -antitrypsin) and 2 000 kDa (factor
if required, is rapidly activated locally (a mat- VIII), most of which are synthesized in the liver
K
K
K
ter of minutes), but an extension of hemostasis (I, II , V, VII , IX , X , XIII, kininogen). Vitamin K
K
is prevented by inhibitory factors (in part is essential for the formation of those factors
K
through a feedback mechanism). The fibrinoly- and proteins marked with a . The vitamin is
Blood sis system is responsible for dissolving exces- important in the posttranslational γ-carboxyla-
sive fibrin clots.
tion of a number of glutamyl residues at the N-
3 Thrombocytes (TCs or platelets; 170– terminal of the peptide chains. These γ-car-
2+
400 × 10 /µL blood) are nucleus-free cytoplas- boxyglutamyl groups are necessary for Ca -
3
tic bud-like particles split off from the mega- mediated fixing to phospholipids, for example,
karyocytes in bone marrow (→ p. 28). Endo- of the thrombocyte membrane (formation of
thelial damage leads, via the von Willebrand complexes).
factor (vWF) to immediate adhesion of TCs to Coagulation (→ D, E). Most coagulation fac-
exposed collagen, which requires, among tors are normally not active. They are activated
other factors, glycoprotein Ib on the TC surface (Index a) by a cascade. Usually the particular
(→ F1). Adhesion activates the TCs, i.e., it factor is converted from its inactive form
causes their aggregation (aided by thrombin), (= proenzyme = zymogen) to an active endo-
changes their form and releases vasoconstric- peptidase which in turn activates the subse-
tive (PDGF, thromboxan A 2 ) and aggregation- quent factor in the same way. The cascade
promoting substances (fibronectin, vWF, fibrin- starts in the environment of the endothelial
ogen). In addition, thromboxan A 2 , together defect (negative charge of subendothelial col-
with ADP (adenosine 5′-diphosphate) that has lagen and sulfatid groups) with contact activa-
also been released, and the inflammation tion of factor XII to XIIa (endogenous activa-
mediator PAF (→ p. 48) enhance TC activation. tion). Factor XIIa then activates PKK to kalli-
When aggregating, TCs contract and greatly krein (KK), which enhances factor XII activa-
change their shape (formation of microvilli), tion (contact phase with positive feedback for
during which the glycoproteins IIb/IIIa (among enhancement). Factor XIIa activates Factor XI
others) are exposed on the platelet surface. to XIa, the latter activating IX to IXa etc., until
This serves the adhesion on fibronectin of the finally fibrin monomers are formed from fi-
subendothelial matrix as well as of fibrinogen brinogen (factor I), these monomers being
that links the platelets together in a net-like bound together covalently by factor XIII
structure (→ F). (transamidase) into a fibrin net. If the injury is
The coagulation system is made up of nu- large, tissue thrombokinase (factor III) comes
merous factors. They include (→ D): into contact with the blood and activates fac-
– factor I (fibrinogen) tor VII, which in a complex with Ca 2+ and
60 – factor II (prothrombin) phospholipids in turn activates factor X (exog-
– factor III (tissue thromboplastin) enous activation).
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Silbernagl/Lang, Color Atlas of Pathophysiology © 2000 Thieme
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