Biochemistry of Hemostasis
or hemostatic response, is the spontaneous
arrest of blood loss from ruptured vessels. In human and
other vertebrate animals, hemostatic response involves
three distinct groups of components. Initially, in what is
generally described as
primary hemostasis,
blood vessels
contract because of the injury and platelets adhere to the
subendothelium. The collagen fibers of smooth muscle
cells and the glycosaminoglycans that form the extracel-
lular matrix beneath the normal endothelium of the blood
vessel become the site of the primary hemostatic response.
Secondly, the platelets form a hemostatic plug that pre-
vents extravasation without occluding the blood vessel.
If vessel occlusion were to occur, it would prevent the
delivery of essential nutrients to the adjacent tissues. Fi-
nally, the hemostatic response includes the actions of the
blood coagulation system, a system that consists of nearly
20 plasma proteins. The sequence of reactions among these
plasma proteins, collectively described as the blood clot-
ting process, produces the enzyme thrombin. Thrombin
then transforms circulating fibrinogen into the fibrin mesh-
work that mechanically reinforces the hemostatic plug.
The reactions of the coagulation system are frequently des-
ignated as constituting
secondary hemostasis.
The char-
acteristics of the hemostatic system that enable it to meet
the requirements for normal hemostasis are as follows: 1
1. It responds rapidly to the injury.
2. It is localized to the site of injury.
3. It is spatially constrained so as not to occlude the
ruptured blood vessel.
4. It is mechanically resistant to disruption by adjacent
blood flow.
5. It creates a temporary structure.
The coagulation system consists of three subsystems.
The “procoagulant subsystem” provides the rapid, local-
ized response to the injury and, because of the enmeshing
of the platelets by fibrin, a hemostatic plug that is spa-
tially constrained and mechanically stable. The “antico-
agulant subsystem” modulates two of the key reactions
of the procoagulant system by inactivating the cofactor
proteins that are components in these reactions. The “an-
ticoagulant subsystem” thus also acts to ensure localized,
spatially constrained response. The “fibrinolytic subsys-
tem,” by proteolytic digestion of the fibrin that reinforces
the platelet (hemostatic) plug, is responsible for the tempo-
rary nature of the hemostatic plug. Digestion of the fibrin
occurs after tissue repair has commenced and the risk of
hemorrhage has been eliminated.
Primary and even tertiary structures are now known
for many of the hemostatic system proteins. Gene struc-
tures have been identified for all of the known compo-
nents of the hemostatic system. Databases listing muta-
tions and their related hemorrhagic or thrombotic risks are
growing rapidly. For many reactions, the molecular mech-
anisms responsible for the properties of the hemostatic
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