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P A R T 8
Drugs acting on the cardiovascular system
the area of the injury. These actions maintain the closed
nature of the cardiovascular system (see Figure 48.3).
Clot resolution and anticlotting process
Blood plasma also contains anticlotting substances that
inhibit clotting reactions that might otherwise lead to an
obstruction of blood vessels by blood clots. For example,
antithrombin III prevents the formation of thrombin,
thus stopping the breakdown of the fibrin threads.
Another substance in the plasma, called plasmin or
fibrinolysin, dissolves clots to ensure free movement of
blood through the system. Plasmin is a protein-dissolving
substance that breaks down the fibrin framework of blood
clots and opens up vessels. Its precursor, called
plas-
minogen
, is made in the liver and is found in the plasma.
The conversion of plasminogen to plasmin begins with
the activation of Hageman factor and is facilitated by a
number of other factors, including antidiuretic hormone
(ADH), adrenaline, pyrogens, emotional stress, physical
activity and the chemicals urokinase and streptokinase.
Plasmin helps to keep blood vessels open and functional.
Very high levels of plasmin are found in the lungs (which
contain millions of tiny, easily injured capillaries) and in
the uterus (which in pregnancy must maintain a constant
blood flow for the developing fetus). The action of plasmin
is evident in the female menstrual flow, in that clots do
not form rapidly when the lining of the uterus is shed; the
blood oozes slowly over a period of days (Figure 48.4).
■■
The transformation of fluid blood into a solid state
to seal breaks in the vascular system is known as
coagulation.
■■
The coagulation process involves vasoconstriction,
platelet aggregation to form a plug and intrinsic and
extrinsic clot formation initiated by Hageman factor
to plug any breaks in the system.
■■
The conversion of prothrombin to thrombin, which
results in insoluble fibrin threads, is the final step of
clot formation.
■■
To prevent the occlusion of blood vessels and the
denying of blood to the tissues, a formed clot must be
dissolved.
■■
The base of the clot-dissolving system is the
conversion of plasminogen to plasmin (fibrinolysin)
by several factors, including Hageman factor. Plasmin
dissolves fibrin threads and resolves the clot.
DISORDERS AFFECTING BLOOD
COAGULATION
Disorders that directly affect the coagulation process are
referred to as haemorrhagic disorders. These disorders
KEY POINTS
fall into two main categories: (1) conditions that involve
overproduction of clots, or thromboembolic disorders;
and (2) conditions in which the clotting process is not
working effectively, resulting in risk for excess bleeding.
Thromboembolic disorders
Medical conditions that involve the formation of
thrombi result in decreased blood flow through or total
occlusion of a blood vessel. These conditions are marked
by the signs and symptoms of hypoxia, anoxia or even
necrosis in areas affected by the decreased blood flow. In
some of these disorders, pieces of the thrombus, called
emboli, can break off and travel through the cardio
vascular system until they become lodged in a tiny
vessel, plugging it up.
Conditions that predispose a person to the forma
tion of clots and emboli are called
thromboembolic
disorders
. Coronary artery disease (CAD) involves a
narrowing of the coronary arteries caused by damage
to the endothelial lining of these vessels. Thrombi tend
to form along the damaged endothelial lining. As the
damage builds up, the lumens of the vessels become
narrower and narrower. Over time, the coronary
arteries are unable to deliver enough blood to meet
Factor X
a
Low-molecular-weight heparin
Bivalirudin
Thrombin
Prothrombin
Antithrombin III
Heparin
A
Plasminogen
(=profibrinolysin;
a plasma protein)
Plasmin (=fibrinolysin)
Facilitated by:
Factor XI
Hageman factor
(=XII
)
ADH
Adrenaline
Pyrogens
Emotional stress
Physical activity
Streptokinase
Reteplase
Anistreplase
Alteplase
Tenecteplase
B
Fibrinogen
Fibrin
Fibrin
clot
Dissolution
of clot
Clot
Antithrombin III
Heparin
Antithrombin III
Heparin
a
a
FIGURE 48.4
A.
Anticlotting process. Antithrombin III (in plasma)
inhibits the activity of Stuart factor (factor Xa) and thrombin;
the drug heparin enhances the activity of antithrombin III. Steps
in clot formation that are inhibited by heparin are shown in
red.
B.
Fibrinolytic process: Clots are dissolved. The step that is
facilitated by the clot-dissolving drugs and by other agents is shown
in blue.
