C H A P T E R 4 8
Drugs affecting blood coagulation
751
T
he cardiovascular system is a closed system, and blood
remains in a fluid state while in it. Because the blood
is trapped in a closed space, it maintains the difference
in pressure required to keep the system moving along.
Everything in the cardiovascular system moves from
higher pressure to lower pressure. If the vascular system
is injured—from a cut, a puncture or capillary destruc
tion—the fluid blood could leak out, causing the system
in that area to lose pressure and changing the flow in
the system, potentially shutting it down entirely. To
deal with the problem of blood leaking and potentially
shutting down the system, blood that is exposed to an
injury in a vessel almost immediately forms into a solid
state, or clot, which plugs the hole in the system and
keeps the required pressure differences intact.
BLOOD COAGULATION
People injure blood vessels all the time (e.g. by coughing
too hard, by knocking into the corner of the desk when
sitting down). Consequently, the vascular system must
maintain an intricate balance between the tendency to
clot or form a solid state, called
coagulation
, and the
need to “unclot”, or reverse coagulation, to keep the
vessels open and the blood flowing. If a great deal of
vascular damage occurs, such as with a major cut or
incision, the balance in the area shifts to a procoagu
lation mode and a large clot is formed. At the same
time, the enzymes in the plasma work to dissolve this
clot before blood flow to tissues is lost, which otherwise
would lead to hypoxia and potential cell death.
Drugs that affect blood coagulation work at various
steps in the blood clotting and clot-dissolving processes
to restore the balance that is needed to maintain the car
diovascular system. Box 48.1 discusses the uses of these
drugs in various age groups.
Clotting process
Blood coagulation is a complex process that involves
vasoconstriction, platelet clumping or aggregation and
a cascade of
clotting factors
produced in the liver that
eventually react to break down fibrinogen (a protein
also produced in the liver) into insoluble fibrin threads.
When a clot is formed, plasmin (another blood protein)
acts to break it down. Blood coagulation can be affected
at any step in this complicated process to alter the way
that blood clotting occurs.
Vasoconstriction
The first reaction to a blood vessel injury is local vaso
constriction (Figure 48.1). If the injury to the blood
vessel is very small, this vasoconstriction can seal off
any break and allow the area to heal.
Platelet aggregation
Injury to a blood vessel exposes blood to the collagen
and other substances under the endothelial lining of the
vessel. This exposure causes platelets in the circulating
blood to stick or adhere to the site of the injury. Once they
stick, the platelets release adenosine diphosphate (ADP)
and other chemicals that attract other platelets, causing
them to gather or aggregate and to stick as well. ADP
is also a precursor of the prostaglandins, from which
thromboxane A
2
is formed. Thromboxane A
2
causes
local vasoconstriction and further
platelet aggregation
and adhesion. This series of events forms a platelet plug
at the site of the vessel injury. In many injuries, the com
bination of vasoconstriction and platelet aggregation is
enough to seal off the injury and keep the cardiovascu
lar system intact (Figure 48.2).
Intrinsic pathway
As blood comes in contact with the exposed collagen
of the injured blood vessel, one of the clotting factors,
DRUGS AFFECTING CLOT
FORMATION AND RESOLUTION
Antiplatelet agents
abciximab
anagrelide
aspirin
cilostazol
clopidogrel
dipyridamole
eptifibatide
prasugrel
ticagrelor
ticlopidine
tirofiban
Anticoagulants
antithrombin III
apixaban
bivalirudin
dabigatran
fondaparinux
heparin
rivaroxaban
warfarin
Thrombolytic agents
alteplase
reteplase
streptokinase
tenecteplase
Other drugs affecting clot
formation
Low-molecular-weight
heparins
dalteparin
enoxaparin
tinzaparin
Anticoagulant
adjunctive therapy
lepirudin
protamine sulfate
vitamin K
Haemorheologic agent
oxpentifylline
DRUGS USED TO CONTROL
BLEEDING
Antihaemophilic agents
antihaemophilic factor,
recombinant
coagulation factor VIIa
coagulation factor VIII
factor IX complex
Haemostatic agents
absorbable gelatin
aminocaproic acid
aprotinin
human fibrin sealant
microfibrillar collagen
