s e c t io n 36.2
Secondary Hemostasis
“procoagulant subsystem” (see below) is providing throm-
bin to activate the platelets. Thrombin activation of
platelets occurs through a unique receptor mechanism
that requires proteolytic action by thrombin followed by
transmembrane signaling via a G-protein-coupled mecha-
nism. Platelet activation causes the release of the contents
of the granules present inside the platelet. The platelet-
dense granules release substances that promote further
platelet aggregation; the alpha granules release several
coagulation proteins that supplement those present in the
Several hemorrhagic disease states are identified from
defects in platelet membrane proteins.
is caused by a defect(s) in Gplb, causing im-
paired binding of von Willebrand factor in the plasma.
The platelet receptor for fibrinogen and fibrin, GpIIb/IIIa,
is defective in
Glanzman’s thrombasthenia.
Figure 36-1C
is a photomicrograph of fibrin-enmeshed activated plate-
lets formed
in vitro.
This illustration is comparable to what
is seen in a normal hemostatic plug. A scanning electron
photomicrograph of resting platelets is shown in Figure
36-1A (top), and a transmission electron photomicrograph
showing internal structures and fibrin strands in associa-
tion with the platelet contractile proteins is shown in Fig-
ure 36-1A (bottom) and in Figure 36-1B. Figure 36-1C is
a photomicrograph of fibrin-enmeshed activated platelets
in vitro.
This illustration is similar to what is seen
in a normal hemostatic plug. In blood, a clot contains ery-
throcytes as well as platelets and fibrin. This type of clot is
similar to that which forms outside the body from a skin-
breaking injury and is similar to “red thrombus” that forms
intravenously. Upon drying the external clot becomes a
scab. An occlusive clot or venous thrombus altogether too
frequently breaks up and is carried to the lung to create a
pulmonary embolus.
36.2 Secondary Hemostasis
Secondary hemostasis refers to the reactions of the blood
clotting factors that are circulating in the plasma
that do
not require platelets.
It is this process that culminates in
the transformation of blood from a readily flowing fluid
to a gel, or, molecularly, the transformation of the solu-
ble protein fibrinogen into the self-assembling, insoluble
polymer, fibrin. The sequence of reactions that makeup
the coagulation system (procoagulant reactions) was de-
scribed as a “cascade” or “waterfall” in 1964. This descrip-
tion, an ordered sequence of transformations of precursor
molecules from their inactive forms to their catalytically
active forms, provided a context in which the hemor-
rhagic deficiencies that had been primarily identified from
patients with bleeding disorders could be understood. This
C u
• S
V il
C l.
/Fibrinogen —
(A lso see color figure.) C lassical “cascade” or “w aterfall” m odel for
coagulation. This m odel represents the ordered sequence o f
in vitro
transform ations o f precursor m olecules from their inactive form s to their
catalytically active form s. The publication o f the “cascade” m odel for the
coagulation system provided a m ilestone in rationalizing a confusing
biological system . The figure has been corrected to place factors V and
VIII outside the linear sequence that differs from the proposals m ade in
1964. Two com ponents, T F (tissue factor) and factor V II, w ere designated
as the “extrinsic pathw ay” com ponents because the TF is provided by
throm boplastin, a tissue-derived m aterial extrinsic to the circulating blood.
Four com ponents— factors X II, XI, IX, and VIII— w ere designated as
“intrinsic pathw ay” com ponents because they are alw ays present in blood.
Two other plasm a proteins— prekallikrein and high-m olecular-w eight
kininogen— w ere discovered later to be involved in the process by w hich
factor XI becom es activated.
conceptualization of secondary hemostasis (clotting cas-
cade) is shown in Figure 36-2.
The “classical” clotting cascade depiction of the proco-
agulant subsystem indicates the order in which the various
factors participate in the process and remains a convenient
mnemonic device. However, this model does not repre-
sent additional properties of the procoagulant subsystem
discovered since its presentation. Our current understand-
ing of the procoagulant process is better represented by
Figure 36-3. The occurrence of the reactions on the sur-
face of membrane lipids, either from cells damaged by
the injury that initiates hemostasis or from exogenous
sources in laboratory tests, is now generally recognized.
Figure 36-3 explicitly acknowledges formation of activa-
tion complexes on the cell surfaces and, by implication,
the tremendous increases in the rates of reactions that oc-
cur in, and only in, the activation complexes. The names
and descriptions of the components of the procoagulant,
anticoagulant and fibrinolytic subsystems are given in
Table 36-1.
Clot Dissolution—Fibrinolysis
The fibrinolytic subsystem, by proteolytic digestion of fib-
rin, eliminates the fibrin from the hemostatic plug. Sim-
ilar to the other subsystems, the fibrinolytic subsystem
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