Page 115 - Color_Atlas_of_Physiology_5th_Ed._-_A._Despopoulos_2003

Hemostasis I Fibrinogen Half-life (h): 96
II K Prothrombin 72
The hemostatic system stops bleeding. Throm-
bocytes (platelets), coagulation (or clotting) fac- III Tissue thromboplastin
2+
tors in plasma and vessel walls interact to seal IV Ionized calcium (Ca )
leaks in blood vessels. The damaged vessel V Proaccelerin 20
constricts (release of endothelin), and platelets VII K Proconvertin 5
aggregate at the site of puncture (and attract VIII Antihemophilic factor A 12
more platelets) to seal the leak by a platelet IX K Antihemophilic factor B; plasma
plug. The time required for sealing (ca. 2 to 4 thromboplastin component (PTC);
min) is called the bleeding time. Subsequently, Christmas factor 24
the coagulation system produces a fibrin X K Stuart–Prower factor 30
meshwork. Due to covalent cross-linking of fi- XI Plasma thromboplastin antecedent
brin, it turns to a fibrin clot or thrombus that re- (PTA) 48
tracts afterwards, thus reinforcing the seal. XII Hageman factor 50
Later recanalization of the vessel can be XIII Fibrin-stabilizing factor (FSF) 250
achieved by fibrinolysis. – Prekallikrein (PKK); Fletcher factor
Platelets (170–400 · 10 3 per µL of blood; – High-molecular-weight kininogen
half-life ! 10 days) are small non-nucleated (HMK); Fitzgerald factor
bodies that are pinched off from megakaryo-
Blood cytes in the bone marrow. When an en- Several coagulation factors are involved in
2+
4 dothelial injury occurs, platelets adhere to the clotting process. Except for Ca , they are
subendothelial collagen fibers (! A1) bridged
by von Willebrand’s factor (vWF), which is proteins formed in the liver (! B and Table).
Factors labeled with a “K” in the table (as well
formed by endothelial cells and circulates in as protein C and protein S, see below) are pro-
the plasma complexed with factor VIII. Glyco- duced with vitamin K, an essential cofactor in
protein complex GP Ib/IX on the platelets are posttranslational γ-carboxylation of gluta-
vWF receptors. This adhesion activates plate- mate residues of the factors. These γ-carboxy-
lets (! A2). They begin to release substances glutamyl groups are chelators of Ca . They are
2+
(! A3), some of which promote platelet adhe- required for Ca -mediated complex forma-
2+
siveness (vWF). Others like serotonin, plate- tion of factors on the surface of phospholipid
let-derived growth factor (PDGF) and layers (PL), particularly on the platelet mem-
thromboxane A 2 (TXA 2) promote vasoconstric- brane (platelet factor 3). Vitamin K is oxidized
tion. Vasoconstriction and platelet contraction in the reaction and has to be re-reduced by
slow the blood flow. Mediators released by liver epoxide reductase (vitamin K recycling).
platelets enhance platelet activation and at- Ca 2+ ions are required for several steps in the
tract and activate more platelets: ADP, TXA 2, clotting process (! B). When added to blood
platelet-activating factor (PAF). The shape of samples in vitro, citrate, oxalate, and EDTA
activated platelets change drastically (! A4). bind with Ca 2+ ions, thereby preventing the
Discoid platelets become spherical and exhibit blood from clotting. This effect is desirable
pseudopodia that intertwine with those of when performing various blood tests.
other platelets. This platelet aggregation Activation of blood clotting (! B). Most coagu-
(! A5) is further enhanced by thrombin and lation factors normally are not active, or zymo-
stabilized by GP IIb/IIIa. Once a platelet genic. Their activation requires a cascade of
changes its shape, GP IIb/IIIa is expressed on events (An “a” added to the factor number
the platelet surface, leading to fibrinogen means “activated”). Thus, even small amounts
binding and platelet aggregation. GP IIb/IIIa of a trigger factor lead to rapid blood clotting.
also increases the adhesiveness of platelets, The trigger can be endogenous (within a ves-
which makes it easier for them to stick to sub- sel) or exogenous (external). Endogenous acti-
endothelial fibronectin.
102 vation (! B2) occurs at an endothelial defect.
XII is activated to XIIa by the contact with
!
Despopoulos, Color Atlas of Physiology © 2003 Thieme
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