Chapter 17
Blood
647
17
reaction sequence. All (except tissue factor) normally circulate
in blood in inactive form until mobilized. Although vitamin K
is not directly involved in coagulation, this fat-soluble vitamin is
required for synthesizing four of the clotting factors (Table 17.3).
Figure 17.14
illustrates the way clotting factors act together
to form a clot. ±e coagulation sequence looks intimidating at
first glance, but two things will help you cope with its complexity.
First, realize that in most cases,
activation turns clotting factors
into enzymes
by clipping off a piece of the protein, causing it to
change shape. Once one clotting factor is activated, it activates
the next in sequence, and so on, in a cascade. (In Figure 17.14,
we use the subscript “a” to denote the activated clotting factor.)
Two important exceptions to this generalization are fibrinogen
and Ca
2
1
, as we will see below.
±e second strategy that will help you cope is to recognize
that coagulation occurs in three phases. Each phase has a spe-
cific end point, as we discuss next.
Phase 1: Two Pathways to Prothrombin Activator
Coagulation may be initiated by either the
intrinsic
or the
ex-
trinsic
pathway
. In the body, the same tissue-damaging events
usually trigger both pathways. Outside the body (such as in a
test tube),
only
the intrinsic pathway initiates blood clotting.
Before we examine how these pathways are different, let’s see
what they have in common.
Serotonin
and
thromboxane A
2
(throm-boks
9
ān; a short-
lived prostaglandin derivative)—messengers that enhance
vascular spasm and platelet aggregation
As more platelets aggregate, they release more chemicals, ag-
gregating more platelets, and so on, in a positive feedback cycle
(see Figure 1.6 on p. 11). Within one minute, a platelet plug is
built up, further reducing blood loss. Platelets alone are suf-
ficient for sealing the thousands of minute rips and holes that
occur unnoticed as part of the daily wear and tear in your small-
est blood vessels. Because platelet plugs are loosely knit, larger
breaks need additional reinforcement.
Step 3: Coagulation
±e third step,
coagulation
or
blood clotting
, reinforces the
platelet plug with fibrin threads that act as a “molecular glue” for
the aggregated platelets (Figure 17.13
3
). ±e resulting blood
clot (fibrin mesh) is quite effective in sealing larger breaks in a
blood vessel. Blood is transformed from a liquid to a gel in a
multistep process that involves a series of substances called
clot-
ting factors
, or
procoagulants
(Table 17.3)
.
Most clotting factors are plasma proteins synthesized by the
liver. ±ey are numbered I to XIII according to the order of their
discovery; hence, the numerical order does not reflect their
Table 17.3
Blood Clotting Factors (Procoagulants)
FACTOR NUMBER
FACTOR NAME
NATURE
SOURCE
PATHWAY; FUNCTION
I
Fibrinogen
Plasma protein
Liver
Common pathway; converted to fibrin
(insoluble weblike substance of clot)
II
Prothrombin
Plasma protein
Liver*
Common pathway; converted to
thrombin (converts fibrinogen to
fibrin)
III
Tissue factor (TF)
Plasma membrane
glycoprotein
Tissue cells
Activates extrinsic pathway
IV
Calcium ions (Ca
2
1
)
Inorganic ion
Plasma
Needed for essentially all stages of
coagulation process; always present
V
Proaccelerin
Plasma protein
Liver, platelets
Common pathway
VI
VII
Proconvertin
Plasma protein
Liver*
Both extrinsic and intrinsic pathways
VIII
Antihemophilic factor
(AHF)
Plasma protein
Liver, lung
capillaries
Intrinsic pathway; deficiency results in
hemophilia A
IX
Plasma thromboplastin
component (PTC)
Plasma protein
Liver*
Intrinsic pathway; deficiency results in
hemophilia B
X
Stuart factor
Plasma protein
Liver*
Common pathway
XI
Plasma thromboplastin
antecedent (PTA)
Plasma protein
Liver
Intrinsic pathway; deficiency results in
hemophilia C
XII
Hageman factor
Plasma protein; activated
by negatively charged
surfaces (e.g., glass)
Liver
Intrinsic pathway; activates plasmin;
initiates clotting in vitro; activation
initiates inflammation
XIII
Fibrin stabilizing factor
(FSF)
Plasma protein
Liver, bone
marrow
Cross-links fibrin, forming a strong,
stable clot
*Synthesis requires vitamin K
Number no longer used; substance now believed to be same as factor V
previous page 681 Human Anatomy and Physiology (9th ed ) 2012 read online next page 683 Human Anatomy and Physiology (9th ed ) 2012 read online Home Toggle text on/off