Arterial Sclerosis

EVALUATION OF INTRAVASCULAR COAGULATION WITH THE HORIZONTALLY AIMED
STEREOSCOPIC MICROSCOPE

After designing the Sclerascope, an adjustable stock for holding the head steady, it was readily
possible to observe the presence or absence of agglomerated in the blood vessels situated in
the white of the eye.  We soon had no difficulty in distinguishing between a low and a high
degree of agglomeration. But what we required was a graduated scale to denote progressively
increasing degree of Intravascular Coagulation (IVC). This necessitated the preparation of
definitions and  ground rules covering the semantics of colloid stability. We attempted to have
these express what is seen with the microscope, and also convey some concept as to the origin
of the forces that brought and held the particles together.

We gradually built up a system of classification, numerically ranging from Grade 1 to Grade 6.  
The former represented no detectable agglomeration or its symptoms; the latter, tremendous
agglomeration, resulting in significant sedimentation in horizontally positioned large diameter
vessels.

Illumination of the left eye is provided by a thin beam of blue-white light, projected almost at right
angles to the line of vision. Light intensity is variable, and heat is removed by a filter.  The head
stock is adjustable in both a vertical and left-right traverse.  The stereoscopic microscope is
positioned horizontally and is adjustable in both vertical and horizontal planes.

The face of the person undergoing examination is held steady and in a frontal position by the
headstock.  The eyes are turned about  15" upward and 45"  to the right, focusing on a target
spot.  This enables the conjunctiva of the left eye (as far as the cornea) to be readily illuminated,
and minimizes glare, eye strain and fatigue.

In selecting an optical system, one might at first assume that the higher the overall magnifying
power the better the view of the blood vessel.  This is not the case.  Available with American
Optical Company's equipment are six fixed objectives, and two eyepieces (15X and 20X).  As the
magnification of the objective is increased, the depth of sharp focus becomes thinner. This
situation is worsened by the natural curvature of the eye, and inability of the person under study
to remain motionless during examination. These considerations are of prime importance
because proper evaluation of the degree of intravascular coagulation depends, to a large extent,
upon how clearly and definitely one can see the flow of blood in the arterioles and venules. It
should be stressed that the microscope must be carefully aligned, particularly with regard to
collimation.

In viewing the white of the eye, one first sees the bulbar conjunctiva; the thin, opaque mucous
membrane covering the anterior portion of the globe of the eye. This membrane is heavily laced
with blood vessels, which are readily viewed with the microscope.  The sclera, the firm fibrous
outer layer of the eyeball, is covered by the conjunctiva. It is likewise heavily laced with visible
blood vessels, but because of their position (to the rear) they do not stand out as plainly as
those in the conjunctiva. Hence the flow of blood in the sclera is somewhat less visible than in
the conjunctiva.

The 1X objective is employed in scanning the conjunctiva and sclera to locate the area
containing the critical vessel or vessels. We term these vessels (and their surrounding areas)
critical because it is here that the physical manifestations of intravascular coagulation are most
clearly revealed, and judgment is made. However, in severe cases, substantially the entire
conjunctiva and sclera give evidence of intravascular coagulation. The location of these critical
vessels will vary from eye to eye, because the vascular pattern of each individual differs to a far
greater extent than the thumbprint. It should be stressed that evaluation is generally made on the
basis of an examination of very few arterioles or venules; and often only one.  Regardless of the
relative degree of coagulation from day to day or week to week, maximum coagulation will
generally be found (in any given individual) in the same venules or arterioles.  This is due to
hydraulic considerations, because these vessels will have optimum diameter, position,
configuration and vascular connections to maximize the manifestations of coagulation.

After selecting the critical vessel (or vessels) with the 1X objective, confirmation and further
study is made with the 2X objective.  The 3X objective is then employed for obtaining an
enlarged and more detailed view of the vessels under examination.  An overall magnification of
60X is necessary for this final evaluation. Consequently ophthalmic microscopes having a
maximum magnification of 30X are generally unsuitable.

One should examine both the conjunctiva and the sclera.  The blood vessels of the conjunctiva
stand out cleaner and are therefore more easily studied.  One will note, however, that clumping is
often more pronounced in the sclera than in the conjunctiva.  This is because frequent blinking
of the eye during an examination tends to mechanically break up agglomerates and clumped
cells in the conjunctiva.  The vessels of the sclera are not affected by blinking.

Appropriate examinations of the conjunctiva and sclera permit evaluations of progressive
stages of intravascular coagulation which are well in advance of cardiovascular emergency
episodes. We have classified seven degrees of intravascular coagulation which we list herein,
with a definition of terms:

Comets

Comet results from a capillary being filled principally with clear plasma, instead of being filled
uniformly with the dart singly or in small groups through the capillary, giving the impression of
shooting stars or comets. The linear spacing from blood cell to blood cell often exceeds five to
ten times the diameter of the capillary.  At times, the capillary may contain only one or two
darting cells. In health, most of the capillaries in service (*) are substantially filled with discrete
cells, and the flow is continuous and uniform. Comets are perhaps the first indication of
intravascular coagulation. It would seem that the reason comets exist is that if every blood cell is
free and discrete, with no agglomeration its distribution in the overall system will be uniform, but
if some cells are agglomerated and some discrete,  It follows that the discrete cells will have
more interstitial space in which to move. (**)   The onset of intravascular coagulation is therefore
characterized by a few darting cells in a few capillaries.  An increased degree of coagulation is
manifested by a greater number of darting cells in a greater number of capillaries. It should be
noted that Comets characterize only the first and second degrees of coagulation, becoming less
noticeable at higher degrees.

Agglomeration

Agglomeration is the condition when blood has partially lost its fluidity and cells flow in rope or
chain-like fashion as though one cell was joined to another. (This is not to be confused with
rouleau formulation. The normal turbulent flow appears to change, as the individual cells lose
their discrete mobility.  This is undoubtedly brought about by a lowering of Zeta Potential, which
results in the formed elements becoming individually enmeshed in the first stages of a fluid gel.
One may also hypothesize that discrete strands of fibrin have formed to sufficient length to
encapsulate the red cells and loosely bind one cell to another.  This cohesiveness imparts a
rope like tendency to the flow pattern, with each cell closely following the path of the preceding
one. One might classify the physical appearance of this blood flow as coarsely granular. This
rope-like flow is in sharp contrast to turbulent flow, wherein each cell stands out boldly and
seems to change its position continually in the general flow pattern. Agglomeration is best
evaluated in arterioles or venues which are 30 to 60 microns in diameter, or 4 to 8 x the size of a
capillary.  Because of opacity, discrete cells cannot be readily seen in the largest veins or
arteries of the eye; and because they move too rapidly, they cannot be satisfactorily observed in
the capillaries.

Stasis

Arteries and arterioles can be distinguished from veins and venues in the sclera and
conjunctiva.  Arteries branch and flow to the (smaller) arterioles, which in turn branch and flow to
the (smaller) capillaries. Thus, the direction of flow follows the branching.

Veins and venules show the opposite pattern. Capillaries flow to the (larger) venules; venules to
the (larger) veins. The direction of flow is, therefore, counter to the direction of branching.

Partial Stasis

Partial stasis is when the rate of blood flow is markedly reduced in arteries, arterioles, veins or
venules. A high degree of stasis is evident when the flow periodically comes to a faltering halt;  
then actually reverses for a few seconds; then sluggishly flows again in its normal direction. In
advanced stasis, a mess of cells may traverse backward and forward in a venule or arteriole for
as long as five to thirty seconds before resuming normal flow. Stasis, in its varying degrees, is
an important criterion in judging intravascular coagulation.

In health, and in the absence of intravascular coagulation, blood flow is brisk, uniform and
unfaltering; from arteries to arterioles to capillaries to venules to veins.  There is no significant
stasis or even temporary reversal of flow.

Clumping

The term 'clumping' is used when cells adhere to each other, forming individual groups of about
5 to 100. In reality, this is a worsening of the condition previously referred to as agglomeration.  
Clumps may be found in arteries, veins, arterioles and venules.  They are not evident in
capillaries, where the small diameter permits red cells to traverse in single file only.  With
clumping, each cluster of cells is separated from its adjacent group by a cylinder of clear plasma.
The length of these clumps is generally two to five times the diameter of the venule or arteriole.  
Conversely, the length of the clear cylinder is more often one or two times the diameter of the
lumen, as shown in the drawing.

Sedimentation of Cells

This condition, which is sketched below, has been thoroughly covered in pictures and text by
Knisely and his associates, and we refer the reader to their published works.

IVC Chart

Forty to fifty percent of the persons in the age bracket of 25 to 65 who were examined by the
writer have shown Grade 3 or higher. One male (age 75) with Grade 5 coagulation, died shortly
after being forced to climb two flights of stairs during the NYC electric power blackout
(November, 195). Another male (age 63) with a known but inoperable tumor of the pancreas was
classified Grade 5. He died of cancer two months later.

The examination of the sclera and bulbar conjunctiva with the horizontally-aimed microscope is
highly essential to the evaluation of intravascular coagulation. There is every evidence that IVC
is closely allied to the physicochemical manifestation of cardiovascular disease.

Minor illness (such as colds or two-day virus) will, in 24 hours, increase an IVC grade of 0-1 to
Grade 3, and occasionally to Grade 4. It is probable that substantially all persons who are gravely
ill with a disease caused by a microorganism will show a degree of Grade 4 to Grade 5.
Indications are that there is some increase in IVC during the menstrual period; and that high
blood pressure (through vasoconstriction) has a tendency to mask intravascular coagulation.

* Krogh showed that under normal conditions of sedentary work or inactivity, only a small
percentage of capillaries (say 10-15) are in actual service.  The percentage of capillaries in
service varies directly with physical exercise and oxygen requirements.  When a person is
undergoing maximum physical exertion, all capillaries are in service.

** The actual volume available for the containment of blood in arteries, arterioles, veins and
venules is controlled to a degree by vasoconstrictors and vasodilators. Thus blood pressure, in
health, is maintained fairly constant (and blood vessels remain filled) regardless of blood volume.

Excerpted from
Control of Colloid Stability Through Zeta Potential
By Thomas M. Riddick
1968 Library of Congress Catalog 67-18001