c h a p t e r 36
Biochemistry of Hemostasis
H l . t k l 3f. I
Platelet niicroanatomy. (A) (Upper) Normal, discoid resting (unstimulated) platelets. (Lower) Resting platelet
cross-section showing the dense tubular system (DTS). glycogen storage granules (Gly). alpha granules (G). open
cannicular system (OCS, “pores" that penetrate into the discoid platelet) and microtubules (MT). (B) (Upper) Platelet
from sample activated by a low dose of thrombin. The cell has lost its discoid form and development internal
transformation. Alpha granules (G) are mainly concentrated in the central area encircled by the coil of microtubules
(MT) and microfilaments (not visible). Magnification is 33,000 times. Upon activation, platelets undergo dramatic
changes; spreading on the surface of the exposed subendothelium, contracting via microtubule action to gather granules
toward the center and releasing microparticles from the platelet membrane. (Lower) Platelets from a clot prepared for
study in the electron microscope while under isometric tension. Fibrin (F) strands and transformed platelets (P) are
closely associated like muscle cells and tendons in order to develop tension. Magnification is 15,000 times. Photograph
is a gift from James G. White, MD, Regents’ Professor, University of Minnesota. (C) Activated platelets are enmeshed
by fibrin strands. Fibrin, shown in cross-section in the activated platelet photograph (C), is shown here as it consolidates
the platelets into a stabilized hemostatic plug. Photograph was the gift of the late Marion I. Barnhart, Wayne State
University, Detroit, Michigan.
response under physiological conditions have been iden-
tified. The underlying premise of this chapter is that un-
derstanding the chemical reactions of hemostasis and their
relationships to the structures of the proteins is the basis
for understanding normal hemostasis, hemorrhagic and
thromboembolic diseases, and their relationships to the
underlying genetic constitution of the individual
. 1
The nomenclature for the hemostatic system components reflects the long
history of the study of blood clotting. The initial identification of coagulation
factors comes from patients suffering from hemorrhagic diseases. The des-
ignation of putative causes of disease as “factors” occurred long before any
information about the molecular structures and functions of the components
was discovered. The Roman numeral designations for the coagulation fac-
tors resulted from the action of a committee that was charged with providing
single designations for factors that were clearly functionally the same but
described by several different names. Because adoption of any of the prior
names might imply priority of discovery, the numerals were assigned as a
compromise. Albeit imperfect, the assignment of single designations for the
coagulation factors was a milestone in advancement of our understanding of
Primary Hemostasis
Primary hemostasis is achieved rapidly as the result of
vasoconstriction of the ruptured blood vessels and the ad-
hesion of blood platelets to the exposed subendothelial
surfaces. Recognition of subendothelial and basal mem-
brane surface components by the platelets occurs through
specific receptors on the external surface of the platelet
membrane. Collagen, present in the subendothelial space,
binds to the platelet receptor GpIa/IIa. The plasma pro-
teins, von Willebrand factor, fibrinogen, and vitronectin
also provide bridging molecules between the exposed
endothelial surface and the platelet. Von Willebrand
factor binds to the platelet via Gpl; fibrinogen binds
via the receptor GpIIb/IIIa. Another platelet protein, gly-
cocalicin, binds the platelets via the receptor GpIb/IX.
platelets to the newly exposed surface is occurring, the
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