C H A P T E R 4 8
Drugs affecting blood coagulation
753
Hageman factor
(also called factor XII), a chemical
substance that is found circulating in the blood, is acti
vated. (Clotting factors are often known by a name
and by a Roman numeral. When one of these factors
becomes activated, the lowercase letter “a” is added;
e.g. activated Hageman factor is also called factor XIIa.)
The activation of Hageman factor starts a number
of reactions in the area: The clot formation process is
activated, the clot-dissolving process is activated and
the inflammatory response is started (see Chapter 15).
The activation of Hageman factor first activates clotting
factor XI (plasma thromboplastin antecedent [PTA])
and then activates a cascading series of coagulant sub
stances called the
intrinsic pathway
(Figure 48.3) that
ends with the conversion of prothrombin to thrombin.
Activated thrombin breaks down fibrinogen to form
insoluble fibrin threads, which form a clot inside the
blood vessel. The clot, called a thrombus, acts to plug
the injury and seal the system.
Extrinsic pathway
While the coagulation process is going on inside the
blood vessel via the intrinsic pathway, the blood that
has leaked out of the vascular system and into the
surrounding tissues is caused to clot by the
extrinsic
pathway
. Injured cells release a substance called tissue
thromboplastin, which activates clotting factors in the
blood and starts the clotting cascade to form a clot on
the outside of the blood vessel. The injured vessel is now
vasoconstricted and has a platelet plug, as well as a clot
on both the inside and the outside of the blood vessel in
Injured
epithelium
releases
factor
A
B
Plug
formed of platelets
and fibrian
Platelets
adhere and
release granules
FIGURE 48.2
A.
Damaged vessel endothelium is a stimulus to
circulating platelets, causing platelet adhesion.
B.
Platelets release
mediators, and platelet aggregation results.
Blood vessel injury
Exposure of blood to subendothelial
collagen, etc.
Tissue injury
Release of tissue thromboplastin
Hageman factor
(XII)
Factor VII
XII
a
VII
a
IX
a
Factor XIII
a
PTA
(XI)
Vitamin K
Intrinsic pathway
Extrinsic pathway
Warfarin
Liver cells
Ca
2+
Ca
2+
Factor VIII
Ca
2+
Phospholipids
Ca
2+
Phospholipids
Factor V
Christmas
factor (IX)
XI
a
Vitamin K
Warfarin
Liver cells
X
a
Vitamin K
Warfarin
Liver cells
Stuart factor
(X)
Vitamin K
Warfarin
Liver cells
Thrombin
Heparin
Prothrombin
(II)
Fibrinogen
(I)
Fibrin
(soluble)
Clot
(insoluble)
Antithrombin
FIGURE 48.3
Details of the intrinsic and
extrinsic clotting pathways. The sites
of action of some of the drugs that can
influence these processes are shown in red.
