Page 339 - Essential Haematology

Chapter 24 Platelets, blood coagulation and haemostasis / 325

soon covers the exposed connective tissue. Th e Coagulation f actor i nhibitors
unstable primary haemostatic plug produced by

It is important that the effect of thrombin is limited

these platelet reactions in the first minute or so fol-
to the site of injury. Th e first inhibitor to act is TFPI

lowing injury is usually sufficient to provide tem-

which is synthesized in endothelial cells and is
porary control of bleeding. The highly localized

present in plasma and platelets and accumulates at
enhancement of platelet activation by ADP and
the site of injury caused by local platelet activation.
TXA2 results in a platelet mass large enough to plug
This inhibits Xa and VIIa and tissue factor to limit

the area of endothelial injury. It seems likely that
the main in vivo pathway by forming the quaternary
prostacyclin, produced by endothelial and smooth

complex. There is direct inactivation of thrombin
muscle cells in the vessel wall adjacent to the area
and other serine protease factors by other circulat-
of damage, is important in limiting the extent of
ing inhibitors of which antithrombin is the most
the initial platelet plug.

potent. It inactivates serine proteases (see Fig. 27.6 ).

Heparin potentiates its action markedly. Another
Stabilization of the p latelet p lug by fi brin protein, heparin cofactor II, also inhibits thrombin.

α 2 - Macroglobulins, α 2 - antiplasmin, C 1 esterase

Definitive haemostasis is achieved when fi brin
inhibitor and α 1 - antitrypsin also exert inhibitory
formed by blood coagulation is added to the platelet
effects on circulating serine proteases.

mass and by platelet - induced clot retraction/
compaction.
Following vascular injury, the formation of Protein C and p rotein S
2 +
extrinsic Xase (VIIa, TF, PL and Ca ) initiates the

coagulation cascade. Platelet aggregation and release These are inhibitors of coagulation cofactors V and

reactions accelerate the coagulation process by VIII. Thrombin binds to an endothelial cell
providing abundant membrane phospholipid. surface receptor, thrombomodulin. Th e resulting
Thrombin generated at the injury site converts complex activates the vitamin K - dependent

soluble plasma fibrinogen into fi brin, potentiates serine protease protein C which is able to destroy

platelet aggregation and secretion and also activates activated factors V and VIII, thus preventing further

factor XI and XIII and cofactors V and VIII. Th e thrombin generation. The action of protein C is
fibrin component of the haemostatic plug increases enhanced by another vitamin K - dependent protein,

as the fused platelets completely degranulate and S, which binds protein C to the platelet surface
autolyse and after a few hours the entire haemo- (Fig. 24.11 ). An endothelial protein C receptor
static plug is transformed into a solid mass of cross - localizes protein C to the endothelial surface, pro-

linked fibrin (Fig. 24.10 ). Clot retraction occurs moting protein C activation by the thrombin –
which is mediated by GPIIb/IIIa receptors which thrombomodulin complex (Fig. 24.11 ). In addi-

link the cytoplasmic actin filaments to surface tion, activated protein C enhances fi brinolysis (Fig.
bound fibrin polymers. Nevertheless, because of 24.11 ).

incorporation of plasminogen and TPA (see p. As with other serine proteases, activated protein
326) , this plug begins to autodigest during the same C is subject to inactivation by serum protease inac-
time frame. tivators (serpins), e.g. antithrombin.

Physiological l imitation of Blood fl ow
b lood c oagulation
At the periphery of a damaged area of tissue, blood
Unchecked, blood coagulation would lead to dan- flow rapidly achieves dilution and dispersal of acti-

gerous occlusion of blood vessels (thrombosis) if the vated factors before fibrin formation has occurred.
protective mechanisms of coagulation factor inhibi- Activated factors are destroyed by liver parenchymal
tors, blood flow and fibrinolysis were not in cells and particulate matter is removed by liver

operation. Kupffer cells and other reticuloendothelial cells.