Pharmacology for Anaesthesia and Intensive Care

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Section IVOther important drugs

Intrinsic and extrinsic pathways

X

Prothrombin (II) Thrombin (IIa)

Fibrinogen Fibrin

Xa

Figure 23.1.Final common pathway of the coagulation cascade.

addition, a fibrinolytic system is activated by tissue damage, converting plasminogen

to plasmin, which converts fibrin into soluble degradation products.

The cell-based model

The cell-based model has been developed more recently in light of the per-

ceived failings of the classical model, in particular its failure to explain haemo-

static mechanisms in vivo. For example, factor XII deficiency does not result in

an increased bleeding tendency in vivo despite abnormal in vitro tests; the bleed-

ing tendency surrounding factor XI deficiency is not closely related toin vitro

tests.

The cell-based model places greater importance on the interaction between spe-

cific cell surfaces and clotting factors. Haemostasis is proposed to actually occur on

the cell surface, the type of cell with its specific range of surface receptors allowing

different cells to play specific roles in the process.

The cell-based model proposes that coagulation is the sum of three processes

each occurring on different cell surfaces rather than as a cascade. The three pro-

cesses areinitiation, amplificationandpropogation.Following vascular injury cells

that bear tissue factor are exposed to the circulation and to circulating clotting fac-

tors thereby initating the process. The limited amount of thrombin generated is

crucial in amplifying the procoagulant signal and causes platelets to become cov-

ered in activated co-factors. The whole process is propogated by the activation of

clotting factors on the surface of the tissue factor bearing cells and platelets. As a

result, large amounts of thrombin are formed leading to the formation of fibrin from

fibrinogen, which consolidates the platelet plug and forms a stable clot. It is this

propogation phase that is so deficient in haemophilia despite relatively normal ini-

tiation and amplification phases because of insufficient platelet surface thrombin

production.