Statement from the Third Quadrennial International Symposium on

Statement from the Third Quadrennial International
Symposium on Quantities and Units in Clinical Medicine—
Paris, November 14-15, 1980
KARL GEORG VON BOROVICZENY, M.D., AND BRADLEY E. COPELAND, M.D.
Laboratory of Clinical Pathology, Krankenhaus Spandau,
Berlin and Department of Pathology, University of
Cincinnati and Veterans Administration Medical Center,
Cincinnati, Ohio
THE COMMISSION ON WORLD STANDARDS
in Clinical Pathology of the World Association of Societies of Pathology (COWS of WASP) organizes symposia from time to time with a view to promote understanding of statements concerning the results of medical
examinations.
International symposia are organized every four
years. The first international symposium on quantities
and units took place in 1972 in Munich, Germany, the
second in 1976 in Gaithersburg, Maryland, and the
third in 1980 in Paris, France. This third symposium
was sponsored by the Bureau International des Poids
et Mesures, Coultronics, S.A., and Du Pont de Nemours, Ltd., The German Institute for Standardization
and Documentation in Medical Laboratories (INSTAND), and by the United Nations Educational, Scientific and Cultural Organization (UNESCO).
To this symposium were invited: Bureau International des Poids et Mesures (BIPM); Commission on
World Standards of the World Association of Societies
of Pathology (COWS of WASP); International Committee for Standardization in Hematology (ICSH); International Federation of Clinical Chemistry (IFCC);
International Standard Organization (ISO); International Union of Immunological Societies (IUIS); International Union of Pure and Applied Chemistry
(IUPAC); United Nations Educational, Scientific and
Cultural Organization (UNESCO); World Health
Organization (WHO); and World Medical Association
(WMA).
Personal invitations were given to selected scientists;
those present included: Prof. Dr. A. Alissy, BIPM,
Paris, France; Mrs. I. Batty, IUIS, London, United
Kingdom; Dr. Ch.-G. de Boroviczeny, Moderator,
COWS of WASP, INSTAND, Berlin, FDR; Prof. Dr.
A. Burlina, COWS of WASP, Verona, Italy; Dr. B.E.
Copeland, COWS of WASP, Cincinnati, Ohio, USA;
Dr. J.X. Dautlick, Du Pont de Nemours, Paris, France;
Prof. Dr. H. Degrelle, COWS of WASP, Paris, France;
Dr. M. Drouard, COWS of WASP, Paris, France; Prof.
Dr. P. Giacomo, Chairman, BIPM, Paris, France; Dr.
A. Frh. v. Klein-Wisenberg, INSTAND, Friborg, FDR;
Mr. P. Lafaye, ISO, Paris, France; Mr. R. Lines, Coulter Electronics, Ltd., London, United Kingdom; Dr.
U.-P. Merten, COWS of WASP, INSTAND, Cologne,
FDR; Prof. Dr. P. Metais, IUPAC, Paris, France; Prof.
Dr. A. Pesce, University of Cincinnati, Cincinnati,
Ohio, USA; Prof. Dr. C. Sultan, ICSH, Paris, France;
Dr. R.L. Verwilghen, ICSH, Paris, France; Dr. L. de
Voss, WMA, Gent, Belgium; Dr. F.G. Weyer, INSTAND, Berlin, FDR; and Dr. R. Zender, IFCC,
Chaux-de-Fohds, Switzerland.
Written statements were submitted by Prof. Dr. H.
Adlercreutz, Meilathi Hospital, Helsinki, Finland; Dr.
F.R. Elevitch, Mount Zion Hospital, San Francisco,
California, USA; Mr. J. Fisher, Med. J. Australia, Sydney, New South Wales, Australia; Dr. P.I.A. Hendry,
Newcastle, New South Wales, Australia; Prof. Dr. P.B.
Herdson, University School of Medicine, Auckland,
New Zealand; Dr. B. Pequero, Universidad, Santa
Domingo; Dr. S.B. Rosalki, Royal Free Hospital,
Hampstead, London, United Kingdom; Dr. G. Santqscoy Gomez, Guadalajara, Mexico; Dr. J.R. Schenken,
Omaha, Nebraska, USA; Dr. N.K. Shinton, Coventry
and Warwickshire Hospital, Coventry, United Kingdom; Prof. Dr. D.B. Tonks, Montreal General Hospital,
Quebec, Canada; and Prof. Dr. A. Videbaek, Amts
Sygehus i. Gentofte, Cobenhavn, Denmark.
Some recommendations were worked out for further
study by international and national organizations and
societies. It was pointed out by some, participants in the
symposium that these recommendations were their per-
Received June 3, 1981; received revised manuscript and accepted
for publication August 3, 1981.
Organized by the Commission on World Standards of the World
Association of Societies of Pathology.
Meetings were held at UNESCO Headquarters, Paris, and at the
BIPM, Sevres, FRANCE.
Address reprint requests to Dr. Boroviczeny: Krankenhaus Spandau, 12, Lynarstrasse, D-1000 Berlin 20, West Germany.
0002-9173/82/0100/0007 $00.75 © American Society of Clinical Pathologists
7
8
VON BOROVICZENY AND COPELAND
sonal opinions, and not necessarily the official position
of the organizations or societies which they represented.
It was agreed that every participant would add some
unedited footnotes in the recommendations. Therefore,
the footnotes are specifically attributed.
The recommendations adopted in Munich, 1972 (Z.
clin. Chem. clin. Biochem. 11:93, 1972), and in Gaithersburg, 1976 (American Journal Clinical Pathology
71:465-468. 1979) should be used in context together
with the present recommendations.
1. Definitions
1.1. Quantities are concepts used for qualitative and
quantitative descriptions of physical phenomena. Such
quantities may be classified into categories, each category containing only quantities that are mutually comparable. If one of the quantities in such a category is
chosen as a reference quantity, called the unit, any other
quantity in this category can be expressed as a product
of this unit and a number, called the numerical value
of the quantity. (ISO 31/0-1974)
1.2. Quantity is a countable or a measurable property expressed as a numerical value times a unit; the
countable or measurable quantity may be discrete or
continuous.
1.3. The system of quantities, which is the base of
SI, includes base quantities and derived quantities. The
derived quantities are expressed in terms of multiplication or division of the base quantities.
1.4. A derived quantity can be expressed by the product of powers of the base quantities. The powers of these
base quantities are called dimensional exponents. In SI,
they are always positive or negative integers.
1.5. In expressing results, decimal powers which are
multiples of three can be substituted for by prefixes,
which are used in connection with the unit. Instead of
some combinations of prefixes and units, special names
are used (e.g., for cubic decimeter, the liter). For the
future, the use of the scientific notation for the numerical value and the use of the SI unit are recommended
(BIPM). The use of prefixes is not recommended because, when using a prefix, a part of the numerical value
is mixed up with the unit (see also section 8.2).
2. Symbol for the Liter
2.1. The 16th Conference Generale des Poids et
Mesures (CGPM #16) adopted, among others, Resolution 6: Recognizing the general principles adopted for
the writing of symbols of units in Resolution 7 of the
9th CGPM (1948), and considering that the symbol
" 1 " for the unit liter has been adopted by the CIPM in
1879 and confirmed in the same Resolution of 1948,
and considering also that, in order to avoid the risk of
A.J.C.P. • January 1982
confusion between the letter " 1 " and the number " 1 " ,
a number of countries have adopted the symbol " L "
instead of " 1 " for the unit liter, and considering that
the name, liter, although not included in the Systeme
International d'Unites, must be admitted for general
use with the System, decided as an exception, to adopt
the two symbols " 1 " and " L " as symbols to be used for
the unit liter. Considering further that in the future
only one of these symbols should be retained, CGPM
#16 invited the CIPM to follow the development of the
use of these two symbols and to give the 18th CGPM
its opinion as to the possibility of suppressing one of
them.
2.2. The participants of the present symposium are
convinced that the general use of the symbol "L" for
liter would be an advance in medicine. Therefore, the
use of this symbol is recommended.*
3. Substance and Mass Concentrations
3.1. The recommendation of the World Health Organization WHO 30.39, adopted May 1977, urges the
adoption of the SI by the entire scientific community
and particularly the medical community throughout the
world. To fulfill this goal, a booklet, "The SI for the
Health Professions," was published in 1977. This booklet is very useful and of great influence.
3.2. The booklet, "The SI for the Health Professions," was followed by some confusion because of the
fact that its introduction 6f the SI in the medical profession was taken to imply the systematic replacement of
mass concentration by the substance concentration.
These are two different quantities which have for each
appropriate SI units. Therefore, many users of the
mass/volume units feel confused since they report data
in SI units.t
3.3. Conversion from mass concentration to substance concentration (unit: mol/L) should occur only
after the widest possible consultation and education
programs.
3.4. If there is a proposed change from one quantity
to another (e.g., mass concentration to substance con* From IFCC: IFCC recommends to continue using the symbol
"1" for liter; motives for change to "L" are not convincing, as most
typewriting machines, including computers, have distinct characters
for "1" and "1." Furthermore, "L" is the symbol for the dimension
of length.
t From IFCC: The kind of quantity "amount of substance" is of
central importance in clinical chemistry. Consequently, IFCC recommends that it be preferred to mass and that derived quantities,
such as substance concentration or substance fraction, are to be preferred to mass concentration and mass fraction, respectively. The
booklet published by WHO, "The SI for the Health Professions,"
according to WHO 30.39 resolution, strengthens and ratifies these
former IUPAC and IFCC recommendations on the proper selection
of kinds of quantities to be used in clinical chemistry.
vol. 77 • No. i
QUANTITIES AND UNITS IN CLINICAL MEDICINE
centration), a task force should collect the advantages
and disadvantages for such a change and publish them.
A similar task force should study the problems arising
from the change from one unit to another (e.g., calorie
to joule).
3.5. The impact of conversion to other quantities or
units on health care should be evaluated. One approach
should be to survey practitioners and clinicians. The
results of these surveys should be published.
3.6. Implementation of changes to SI units or to
other quantities within the SI for an analyte or groups
of analytes should take place expeditiously, e.g., new
quantities should replace old ones and not appear simultaneously.
4. Instrumentation
4.1. It is recommended that manufacturers design
instruments in which parameters such as temperature,
time, and volume can be varied to follow the evolution
of international standards.
5. Enzymes
5.1. Catalytic activity of an enzyme is a property
measured by the catalyzed rate of conversion of a given
chemical reaction, produced in a specified assay system.
It would be advantageous also to express enzyme in
terms of mass or amount of substance, specifying
whether the protein is active or inactive.
5.2. The coherent derived SI unit to be used for
measurement of enzyme activity is mole/second (mol/
s). The special name proposed for this unit by IUB,
IFCC and IUPAC is katal (kat). The international unit
(U) is equal to one micromole per minute and equal to
16,67 nanokatal (1 U = 1 umol/min = 16,67 nkat); it
is not a coherent SI unit. At the present time, the international unit (U) is in wide use. The changeover to
kata| may be synchronized with the adoption of optimized methodology. (Note: All multiples or submultiples of SI base units are noncoherent SI units. Only
base SI units are coherent SI units.)
5.3. For practical and scientific reasons, agreement
on a single temperature has not been obtained throughout the medical and scientific community. The most
frequent proposals are 25°C, 30°C, and 37°C; 30°C
is recommended by IFCC. The accuracy of temperature
control is of prime importance. The temperature referred to should always be reported.
6. Toxicology
6.1. It is recognized that there is a growing important
field of therapeutic drug monitoring. It is recommended
that: 6.1.1. The same kind of quantity should be used
9
for dosage of a drug and for its measurement in human
fluids and tissues;! 6.1.2. In the expression of concentrations or contents, the numerator value should not
change, irrespective as to whether the chosen unit is
milliliter, liter or cubic meter, or kilogram;! and 6.1.3.
Where confusion is possible with the symbols "m,"
*V»" " n >" i t ' s recommended that prefix names "milli,"
"micro," "nano," be completely spelled out.
7. Blood Gas Pressure and pH
7.1. The quantity pH has the dimension and thus the
unit " 1 . "
7.2. For the expression of results of measurement of
partial pressures or pressures of gases, the unit pascal
(Pa) is recommended.
8. Hematology
8.1. The use of the Systeme International d'Unites,
SI, in expressing quantities of all hematologic analytes
including-hemoglobin, is supported. It is agreed that,
within SI, the use of mass, amount of substance, mass
concentration, and substance concentration are equally
acceptable modes of expressing laboratory determination results. In practice, the results of the determination
of hemoglobin are expressed, worldwide, with a few
exceptions, as mass concentration. There has been no
convincing proof offered of any advantage in using substance concentration as a practical clinical level, nor
have convincing arguments been advanced to persuade
hematologists to prefer substance concentration. Accordingly, hemoglobin determination results should be
expressed in mass concentration, g/dL or g/L or g/m 3
(e.g., 14 g/dL or 140 g/L or 14.104 g.nT 3 ). ICSH recommends g/L. If, for scientific studies, individual workers prefer to express hemoglobin measurement results
in amount of substance or in substance concentration,
the elementary entity used should be defined as the
hemoglobin monomer.§
8.2. There are certain deficiencies in expressing results of enumeration of blood cells, as different modes
of expression are in use.
"8.2.1. Originally, erythrocyte count results were expressed in millions per cubic millimeter (or microliter),
and leukocyte or platelet counts in thousands per cubic
millimeter (or microliter), e.g., B-erythrocyte particle
t From IFCC: IFCC recommends that drugs be expressed using
the same kind of quantity as for endogenous compounds, i.e., "amount
of substance" rather than mass. Substance concentration of drug
should be expressed in moles (or multiples: mmol, /imol, etc.) per liter.
§ From IFCC: IFCC advocates the use of the kind of quantity
"amount of substance" for the expression of hemoglobin and thus also
of substance concentration in moles (or multiples) per liter. A number
of pertinent chemical and clinical arguments militate in favor of this
position.
10
VON BOROVICZENY AND COPELAND
concentration: 4,25 millions/mm 3 = 4,25 X 106 X mm"3;
B-leukocyte particle concentration: 7,2 thousands/mm 3
= 7,2 X 103 X mm - 3 ; and B-platelet particle concentration: 235 thousands/mm 3 = 235 X 103 X mm - 3 .
8.2.2. It also was proposed (by ICSH, IUPAC and
IFCC) to give the results per liter or (by others) per
cubic meter, e.g., B-erythrocyte particle concentration:
4,25 X 10' 2 X L _ l = 4,25 X 1015 X m"3; B-leukocyte
particle concentration: 7,2 X 109 X L"1 = 7,2 X 1012
X m~3; and B-platelet particle concentration: 235 X 109
X L"1 = 235 X 1012 X m" 3 .
8.2.3. As a more simple expression, it was recommended that the use of convenient submultiples of the
volume measure, the liter, should be adopted, e.g., Berythrocyte particle concentration: 4,25/pL; B-leukocyte particle concentration: 7,2/nL; and B-platelet particle concentration: 235/nL.
8.2.4. As blood cell counts are particle concentrations, or mixed phases, the quantities and units of both
phases should be mentioned in the equation when results
are expressed. Therefore, the Bureau International des
Poids et Mesures was invited to consider the advantages
of introducing a new unit for use within SI, for the
expression of results of counting; such a unit could then
be used with the accepted SI prefixes also. Such a unit
would be useful in many fields of medicine, including
hematology, microbiology, and radiology. BIPM would
be kept informed of the development of the use of such
a unit, if it should be adopted in various countries. It
was agreed that such a unit could be name "entity" and
abbreviated "e«/."* There are different ways in which
to use this unit: 8.2.4.1. Particle concentrations may be
expressed in particles per volume. The coherent SI units
would be entity per cubic meter (ent X m~3), e.g., Berythrocyte particle concentration: 4,25 X 1015 X ent
X m" 3 = 4,25 petaentitiesf ([Pent] X m" 3 ) B-leukocyte
particle concentration: 7,2 X 1012 X ent X m~3 = 7,2
teraentities ([Tent] X m~3) B-platelet particle concentration: 235 X 1012 X ent X m" 3 = 235 teraentities
([Tent] X m~ 3 ). 8.2.4.2. As noncoherent SI units, multiples of the entity and the liter could be used, e.g., BRBC particle concentration = 4,25 Tent/L; B-WBC
particle concentration =. 7,2 Gent/L$; and B-platelet
particle concentration = 235 Gent/L. 8.2.4.3. In print,
the scientific notation shouuld be given, printing the
powers as usual (e.g., 1012). When typewriting a result,
* From IFCC: IFCC considers that a proposal for a new name for
"unity," "entity," or "one" is'premature. A joint ICSH, IUPAC, and
IFCC party is working on the subject that proved itself more difficult
than was anticipated. Currently, expression of number concentration
should follow the scheme proposed in section 8.2.2.
t Note the abbreviation for petaentities uses "P" from peta and
"ent" from entity as an abbreviation or unit symbol.
t Note that G = giga and M = Mega.
A.J.C.P. 'January 1982
or in computer printouts, the exponents are declared
in a different way, where E stands for "exponent of the
base 10," e.g., B-RBC particle concentration = 4,25E12
X LE-1; B-WBC particle concentration = 7,2E9
X LE-1; and B-platelet particle concentration = 235E9
X LE-1.
8.3. It is highly desirable that results of the leukocyte
differential count be reported as particle concentrations
(so called absolute numerical values), and that the practice of reporting results as percentage or fraction should
be discouraged. It is recommended that values be reported per cubic meter, or per liter, e.g.,
B-WBC particle concentration = 7,2 Gent/L
B-stab. neutro. concentration = 140 Ment/Lf
B-Poly neutro. particle concentration = 3700
Ment/L
B-Poly eosino. particle concentration = 210 Ment/L
B-Poly baso. particle concentration = 70 Ment/L
B-Monocytes particle concentration = 420 Ment/L
B-Lymphocytes particle concentration = 2600
Ment/L.
8.4. The term hematocrit is used for the volume fraction of erythrocytes in the blood (leukokrit for leukocytes). When recording the hematocrit, the method
used must be indicated in brackets. The term "Packed
Cell Volume" (PCV) should be kept for centrifugation
techniques only. All methods involving sample dilution
should include information relevant to the cell shape
during measurement (e.g., pH, osmolality, ionic strength,
etc.). Results are expressed as volume fraction, the coherent unit is the cubic meter per cubic meter (m 3
X m - 3 = m°).§ A noncoherent SI unit is the liter per
liter (L 3 X L" 3 = L°), e.g.,
B-Ery, volfract 0, 45 m° = 0,45 L° = 0,45 LEO.
8.5. The kind of quantity erythrocyte sedimentation
rate is a variable velocity; therefore, results are expressed as length (in m, or mm) in fixed times (60 min,
120 min).
8.6. The results of the determination of blood or
plasma viscosity are expressed as Pa X s (pascal-second) = N s X m~2 (newton-second per square meter).
When recording the blood viscosity, the shear-rate during the measurement must be indicated..
8.7. The use of a variety of arbitrary units for expressing results of coagulation measurements should
ultimately be discouraged. However, at this time, specific recommendations for appropriate SI units can only
be made for a few determinations, e.g., the use of the
§ From IFCC: The kind of quantity "volume fraction" is the volume
of an isolated component divided by the volume of the system. This
kind of 1quantity has the dimension one and the coherent unit is
"unity". The unit "liter per liter" (or the derived coherent unit "cubit
meter per cubic meter") is a redundant alternative.
Vol. 77 • No. 1
QUANTITIES AND UNITS IN CLINICAL MEDICINE
second in prothrombin time measurement; the use of
the minute in bleeding time determination. The need
of widely accepted reference materials, e.g., thromboplastins and reference plasmas, is stressed.
9. Immunology
9.1. Immunologists agree that SI units should be
used in all situations where they are appropriate.
9.2. In the current state of the art, however, experience has shown that more precise and accurate results
are obtained when the results are recorded in international units of biological activity in comparison with the
appropriate international standard (WHO) or in comparison with National Standards, which have been calibrated in terms of the International Standards.
9.3. A great amount of investigation is taking place
with the aim of producing pure stable monospecific antigens and antibodies in order as soon as the state of
the art warrants to express these immunologically measured high molecular weight proteins in the first instance as g/L; later, it is hoped as mol/L, taking account of the number of active binding sites.
10. Microbiology
10.1. Being aware of certain deficiencies accompanying the expression of results of enumeration of microorganisms in multiples of the number 10, indicated
as exponents to the number 10, the participants agreed
to promote the use of convenient submultiples or preferably the use of the unit "entity" (as shown in section
8.2.4.).
10.2. Being aware of the deficiencies in expressing
the amount of antibodies by means of serum dilutions,
11
the participants agreed that it cannot be avoided for
the time being. However, they believe that titers should
be stated as the volume fraction of serum, introduced
in the applied method, and they discourage the use of
dilutions reached at the end of the test procedure. The
need of widely accepted reference materials (monospecific antisera against different antigens) was stressed.
11. Permission to Publish
11.1. All national health authorities, professional societies, and manufacturers of laboratory equipment and
reagents are invited to translate these recommendations
into their native language, publish the translations, and
distribute them in context together with the recommendations of the previous International Quadrennial
Symposia on Quantities and Units.
12. Recommendations for the Future
12.1 Symposia, workshops, and conferences should
be organized in all parts of the world to discuss the
different problems of quantities and units in clinical
medicine.
12.2. The World Health Organization is also invited
to publish a reviewed issue of the booklet, "The SI for
the Health Professions."*
* From IFCC: IFCC does not agree that a revision of the WHO
booklet, "The SI for the Health Professions" is currently needed. It
recommends, on the contrary, that the principles and detailed proposals contained in this document be implemented. Supplements could
be published when necessary, for instance, concerning the quantities
and units in enzymology. Please address your comments to: Dr.
Ch.-G. de Boroviczeny, Co-Chairman, Commission on World Standards (COWS) of the World Association of Societies of Pathology
(WASP), Lynarstrasse 12, D-1000, Berlin 20, West Germany.