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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

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

hemostasis.

36.1

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.

At

virtually

the

same

time

that

adhesion

of

the

platelets to the newly exposed surface is occurring, the