anelectron microscopic description ofbasophilic stippling inred cells
Post on 12-Sep-2021
4 Views
Preview:
TRANSCRIPT
An Electron Microscopic Description of Basophilic
Stippling in Red Cells
By WALLACE N. JENSEN, GIULIANA D. MORENO AND MARCEL C. BEssis
I HE FIRST DESCRIPTION of basophihic stippling in erythrocytes was
made by Ehrhich1 and the association of basophilic stippling with lead
intoxication followed shortly thereafter.2 Numerous studies of basophilic
stippling and its occurrence in a variety of hematologic disorders followed
these original descriptions. Various early investigations indicated that the
substance which forms the punctate basophilia in the red cell is derived
from the nucleus or from various cytoplasmic components or from the red cell
membrane.3’4 More recent studies suggest that basophilic stippling occurs only
in young erythrocytes and that cells with hasophibic stippling have common
properties with reticubocytes.a� The comprehensive studies of Dustin7 resulted
in the conclusion that the stipple material is composed exclusively of ribo-
nucleoproteins. Others have suggested that punctate stipple material is corn-
posed of ribonucleoproteins plus mitochondria or ribonucleoproteins and
portions of the red cell membrane. Others have suggested that nonheme iron
may constitute a part of the basophihic stipple substance.8’#{176} The work of
Bruckner1#{176} and that of Dustin7 indicate that basophihic stippling does not
exist in cells suspended in plasma, but occurs when cells which contain the
necessary precursor components are subjected to certain manipulations during
the preparation of the blood for microscopic examination.
These studies describe basophilic stippling as observed with the combined
use of supravital stains, light microscopy and electron microscopy. A pre-
liminary report of the findings has appeared elsewhere.�’
MATERIALS AND METHODS
Lead intoxication was produced in guinea pigs, rabbits and rats by the subcutaneous
injection of 4 per cent lead acetate in water in amounts of 200 to 400 mg. per Kg., given
in single or multiple injections during a period of less than 7 days. Hematologic abnormal-
ities appeared within 2 to 4 weeks. Blood was also examined from patients with lead in-
toxication and other types of hemolytic anemia.
Blood was used, with or without heparin, for routine smears and electron microscopy.
When advantageous, young cells were concentrated by centrifugation (600 g. for 10
minutes). Reticulocyte preparations were made by mixing equal amounts of blood and
dye (0.5 per cent New Methylene Blue dye in a 0.7 per cent solution of sodium chloride)
for 5 minutes, after which smears were made, fixed with alcohol and stained with Giemsa
solution.12 For the preparation of stippled cells by the action of dye, equal amounts of
New Methylene Blue of various concentrations (0.025 to .008 per cent) and blood were
mixed for 45 seconds following which smears were made for light microscopy, or the
From the Centre National de Transfusion Sanguine, Paris, France and the Department
of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
Supported in part by grant (HE-06270) from the U. S. P. H. S., Bethesda, Maryland.Submitted July 3, 1964; accepted for publication Oct. 26, 1964.
933
BLOOD, VOL. 25, No. 6 (JuNE), 1965
For personal use only.on April 12, 2019. by guest www.bloodjournal.orgFrom
934 JENSEN, MORENO AND BESSIS
dye and blood mixture was centrifuged and the cells resuspended in native plasma prior
to fixation for electron microscopy. Blood and bone marrow were fixed in Daltons’ solu-
tion, dehydrated in alcohols and embedded in Epon. The sections were mounted on
formvar, stained with lead acetate and examined by electron microscopy. Dried fixed bloodsmears were stained with LOfflers methylene blue dye for basophilic stippling’3 and by the
Prussian blue reaction for nonhenie iron (leposits. Ribonuclease studies were done by
treatment of cells on dried smears with an 0. 1 per cent solution of a commercially avail-
able enzyme#{176} at pH 6.4, for 15 to 30 mnintites at 45 C.
RESULTS
Blood or bone marrow cells from 20 rabbits, 20 guinea pigs and 60 rats were
examined by one or more technics, usually on multiple occasions. There was
marked variation in the time of appearance and in the number of stippled
cells present. Stippling was always found in the bone marrow when it was
present in the peripheral blood, b�t was found only in the orthochromatophilic
normoblasts which were relatively few in the animals with severe lead in-
toxication.
Optical Microscopy
Relations of Basophilic Stippling, Reticulocytes and Polychrornatophilic
Cells. Examinations were made on samples of blood which had greatly varied
numbers of reticulocytes and degrees of pol�chromatophilia. The number of
basophilic stippled cells was always less than the number of reticubocytes.
In a single sample of blood the number of stippled cells varied from one
slide to another and in various parts of the same smear. A greater number of
stippled cells was present in thicker than in thinner parts of the smear, and
blood films which were dried rapidly had fewer stippled cells than those dried
slowly. The difference in numbers of stippled cells in a sample of blood was
accentuated by drying blood films very rapidly and very slowly. Slow drying
was accomplished by use of a humid chamber as described by Dustin.7 Stippled
cells induced by the humid chamber had morphologic characteristics identical
to those found on randomly prepared or rapidly dried smears. Stippling was
produced by slow drying not only in lead intoxicated animals, but also in
the bloods of animals with phenylhydrazine and phlebotomy-induced reticulo-
cytosis.
The number of stippled cells was also increased by the incubation of blood
with various concentrations of New Methylene Blue dye (less than O.2�5 per
cent). Basophilic stippled cells were produced when an abundance of young
cells were present whether due to lead poisoning, phenylhydrazine intoxica-
tion or prior phlebotomy. The appearance of the stippling was identical to
that of blood specimens prepared by conventional methods. The converse or
production of reticulocytes to the exclusion of cells with basophihic stippling
was attempted. Samples of bbocd were incubated with concentrated New
Methylene Blue dye (0.25 per cent) for 5 minutes. In dried smears prepared
#{176}L.Light and company Ltd., Colnbrook, England.
For personal use only.on April 12, 2019. by guest www.bloodjournal.orgFrom
BASOPHILIC STIPPLING IN RED CELLS 935
from such blood samples, only cells which had the typical appearance of
reticubocytes were seen. Thus the arrangement of basophilic material in
either round multiple regular masses, as seen in stippled cells ( fig. 1A ) or in
irregular serpentine networks as seen in reticulocytes ( fig. 1 B ) may be
produced by the interaction of appropriate proportions of New Methylene
Blue dye and the basophilic material within young red cells.
There was increased ultraviolet light absorption of the stippled points and
of a diffuse nature throughout the cytoplasm of the polychromatophilic cells
in dried blood smears. Punctate basophilia was not seen with ultraviolet
light in plasma suspended cells. Examination of dried smears with light in
the Soret band showed negative absorption scattered in the cell in punctate
arrangements.
Treatment of blood smears with ribonuclease, caused a loss of the basophilic
punctuation, diffuse basophilia and reticubocyte skeins.
The Relationship between Baso’philic Stippling and Siderocytes. The rela-
tion of nonheme iron and basophilic stippling was examined in two ways.
A comparison of the number of siderocytes and cells with basophilic stippling
was made, and single intracellular basophilic stipple points were localized
and restained for nonheme iron. There was no constancy between the number
of siderocytes and cells with hasophilic stippling. In single cells, it was not
always possible by light microscopy to determine whether a basophilic stipple
point, when restained for iron, was of the exact same size and location. Single
basophilic points were found which were positive, and others negative for
iron. There were iron positive deposits which were negative with the baso-
philic stipple stain. Thus, by supravital stains and by light microscopy there
was no constant association between nonheme iron deposits and basophilic
stippling.
Electron Microscopy
Abnormalities in normoblasts and reticubocytes of animals with lead poison-
ing were of multiple types and frequent occurrence. Those which do not
specifically constitute a part of basophilic stippling will only be listed here
and will be described in detail in another publication. There were abnormal
densities, irregular in outline and eccentrically located in the erythroblast
nuclei. There was widening of nuclear membrane pores with concentric
lamellated myelin bodies at the juncture of the nuclear membranes and mito-
chondria. The Golgi apparatus was greatly enlarged. Many mitochondria
were seen, which were greatly enlarged, dilated, devoid of normal cristae, and
often contained large amounts of ferritin or ferruginous micelles. Ferritin in
scattered and aggregate forms was present in cytoplasm and in discrete
vacuoles or in double membrane lined tracts and in invagmations of the cell
membrane.
Polyribosomes and monoribosomes were evenly distributed in the cytoplasm
of the reticubocytes. It was not possible in these studies to accurately quantitate
the proportions of each type of rihosome.
For personal use only.on April 12, 2019. by guest www.bloodjournal.orgFrom
A B
JENSEN, MORENO AND BESSIS
09
Fig. 1.-(A) Basophilic stippling produced in young, non-nucleated red cells bysupravital stain (dilute New Methylene Blue). Smears of cells were stained withGiemsa stain and examined with a low phase contrast objective. (B) Reticulocyteswith supravital stain (concentrated New Methvlene Blue). The blood smears werestained with Giemsa stain.
Blood specimens from all animals were searched by electron microscopy
for intracellular structures which might be interpreted as basophilic stippling.
Although basophilic stippling was present in large numbers when smears were
prepared and examined with the optical microscope, they were never seen
when the blood was prepared in routine fashion for electron microscopy.
Blood with high percentages of reticulocytes, from animals with lead
poisoning, phenylhydrazine-induced anemia and postphlebotomy anemia were
incubated with various concentrations of new methylene blue dye, and when
basophilic stippling was found by optical microscopy, similar preparations
were made for electron microscopy.
Blood samples were examined with and without prior incubation with new
methylene blue dye. In the specimens without supravital staining, there were
reticulocytes with mitochondria and evenly dispersed ribosomes (fig. 2). In
the specimens with supravitally stained cells, there were aggregated ribo-
somes, which formed irregular networks (fig. 3). In the supravital stained
preparations still other cells were seen, which contained multiple, round or
For personal use only.on April 12, 2019. by guest www.bloodjournal.orgFrom
- 5:
..�1
r
V
BASOPHILIC STIPPLING IN RED CELLS
.�
I,
�
.5 .
5- #{149}�‘ -. .‘ - . 5�_#{149}-S. � #{149} 5. S- -v
.,� .�,-..#{149}
-#{149} #{149}� .. . ...
� �
937
Fig. 2.-Electron microscopic photograph of a reticulocyte without supravital
stain. Ribosomes are evenly scattered in the cytoplasm, mitochondria are present
and the cell outline is irregular. Mag. x 32,600. (Reproduced from1 4)
irregularly round aggregates of rihosomes without other scattered cvtoplasmic
ribosornes (fig. 4A, B).
The majority of cells with (lot-like aggregates of ribosornes also had
mitochondria. The mitochondria had no constant positional relation to the
ribosomal aggregates. The hasophilic stipple material of the cell does not,
therefore, include mitochondria. Not infrequently, nonheme iron-laden mito-
For personal use only.on April 12, 2019. by guest www.bloodjournal.orgFrom
‘V
., -�,_#{149}t�-’:.; -
-�
I � �
,d.�
.�r:
938 JENSEN, MORENO AND BE.SSTS
#{149} ,4#{149}�_ .
- � �-, #{149}-
�. 2.:
L ‘ �.. �. .5,
- #{149}‘�:� - -
� � - ‘:�,�.,, - ‘S �S�’
�5-5,� � 5#{149}* 4I,. � � #{149}- � -#{149} - ‘ : #{149}
- -S
Fig. 3.-Electron microscopic photograph of a reticulocyte after supravital stain(concentrated New Methylene Blue). The ribosomes are aggregated in linear and
skein-like networks. Mitochondria are present. (Reproduced from’4)
chondria were located adjacent to ribosomal aggregates, but were clearly
separate from the ribosomes (fig. 5). The two structures could be separately
identified only with magnifications afforded by electron microscopy. Blood
films were prepared on glass slides, removed by scraping with a razor and
prepared for electron microscopy. These cells were greatly distorted, not ideal
for examination and showed nonheme iron deposits, but were without identi-
fiable mitochondria or ribosomes.
For personal use only.on April 12, 2019. by guest www.bloodjournal.orgFrom
� �
I
I
__.5.
�
- I,..
1�’ -. -
#{149}� �#{149}#{149}-�. ,,-�.
,*. S. � -� ,4r� ,
� ‘:‘�-
O,5p-‘-4
BASOPHILIC STIPPLING IN RED CELLS 939
I
Fig. 4.-(A) Electron microscopic photograph of a young reticulocyte after supra-vital stain with dilute New Methylene Blue dye. The ribosomes are aggregated andin punetate forms but are independent of mitochondria which are also clearly seen.
Discussiox
The affinity of the stippled material of young erythrocytes of lead intoxicated
animals for basic dyes, the absorption of ultraviolet light and the disappear-
ance of the basophilic material following treatment of the cells with ribo-
nuclease have been describe(l previously.7 Identical findings have been
described in the reticulocyte,14 and indicate strongly that stippling is composed
either wholly or in part of ribonucleoproteins. The production of greater or
smaller numbers of basophilic stippled cells by slow or rapid dessication of
the blood film and by incubation with various concentrations of new
methylene blue strongly suggests that the three morphologic entities (retic-
ulocytes, diffuse polychromasia and punctate hasophilic stippling) are the
result of different manipulations of the cell in preparation for optical or
electron microscopy. These same factors may partially explain the variable
numbers of cells with punctate basophilia which may be found on different
blood films made from the same blood.5’7’10 The number of siderocytes and
their lack of constancy as well as the number of basophilic stippled cells in
a sample of blood and the different locations within a cell of basophilic
For personal use only.on April 12, 2019. by guest www.bloodjournal.orgFrom
Fig. 4.-(B) The same section as figure 4(A) but with greater magnification,which allows a more discrete view of aggregate ribosomes and mitochondria.
940 JENSEN, MORENO AND BESSIS
.1- �‘� � S - ,,�
� L �‘�#{149} ‘#{149} S
I �
- :?�: -S ‘�, #{149} -� �1.%� � �#{149}.�4’ . 5 5- - - � �- y --�
�* � � S Lr- .‘._- S ‘5 5
-� - 5. -. -.5.-- -‘5- -
�
stippling and iron have been noted in previous studies and was confirmed.15
The arrangement of iron-laden mitochondria and ribosomal aggregates
within the cell was sometimes such that they could not be resolved as two
distinct structures by light microscopy. The occurrence of nonheme iron in
a stipple point is therefore fortuitous and results from the superimposition or
juxtaposition of the two separate structures. This is best appreciated when the
cells are examined by electron microscopy. Prior studies7’15 and the present
one indicate strongly that nonherne iron is not an essential component of
basophilic stippling.
It seems that the multiplicity of different conclusions which have been
reported concerning the nature of basophilic stippling3’4’6”548 may have
derived in part from the variable methods used for preparation and examina-
tion of cells. In the present study, the evidence indicates that only the
ribosomal aggregates seen by electron microscopy in the young red cells from
animals with lead poisoning, constitute the hasophilic stipple.
The peculiarity of the basophilic stippling which occurs classically in lead
poisoning, but also in a variety of other diseases is that it occurs “spontane-
ously.” It might, therefore, he properly suggested that the occurrence of baso-
philic stippling is evidence of ribosomal abnormality.
The abnormalities of function of ribosomes in thalassemia described by
Burka and Marks19 and other biochemical and clinical similarities between
lead poisoning and thalassemia make attractive a suggestion of the possibility
For personal use only.on April 12, 2019. by guest www.bloodjournal.orgFrom
‘�1
14�.
‘1.1
- S.
#{149}m�’�’; �
�1 �
Fig. 5.-Electron microscopic photograph of a young non-nucleated erythrocyte
from a rat with lead intoxication. The cell was stained supravitallv with dilute New
Methvlene Blue dye prior to fixation for electron microscopy. Punctate aggregates
of ribosomes are adjacent to dilated mitochondria which contain iron deposits. Amass of cvtoplasmic ferritin is also present.
BASOPHILIC STIPPLING IN RED CELLS 941
I,
SI.-.-,.
IS ‘
�1 .-.� �
..‘ #{149}- :‘ .‘,::
.. - ,, . ,,#{149}�:.i’, ‘#{149} S � S
--‘v’ �‘�#{149}
SI-.� � S ‘‘
‘-S
#{189}
of functional abnormalities of ribosomes in erythrohlasts and reticulocytes of
animals with lead poisoning. However, the known multiple biologic actions
of lead also allow the possibilities of a primary alteration of red cell mem-
brane20’2’ or nonribosomal organelles22 or other substances in the interior of
the cell23 which then cause ribosomes to agglutinate. Qualitative structural
abnormalities of red cell ribosomes are difficult to evaluate by electron
microscopy since the ribosomes vary in type and numbers with stage of
maturation of the red cell.
CONCLUSION
Red cells which contain ribosomes presumably have the potential to form
stippled cells. The rihosomes in cells from animals with phenylhydrazine and
postphlebotomy anemia may form stippling when blood films are dried slowly
or when stained supravitally with dilute concentrations of New Methylene Blue
dye. The ribosomes of cells from animals with lead intoxication have a greater
propensity to form aggregates and therefore to result in stippling.
Since the formation of stippling in cells is dependent on the dessication of
cells, they are not seen in plasma suspended cells nor in cells prepared in
routine fashion for electron microscopy. The basophilic stippled material
For personal use only.on April 12, 2019. by guest www.bloodjournal.orgFrom
942 JENSEN, MORENO AND BESSIS
produced in certain blood cells by the action of supravital dye consists exclu-
sively of ribosomes. The association of nonheme iron with basophilic stippling
is usually the consequence of the presence of two separate morphologic struc-
tures within the cells which may not be resolved, one from the other, in light
or phase microscopy, but may be distinguished by the use of electron micro-
scopy.
The “spontaneous” occurrence of the hasophilic stippling may be interpreted
as evidence of ribosomal abnormality, hut the multiplicity of cellular injuries
induced by lead, other chemicals, drugs or disease processes may indicate that
rihosomal aggregation results from alteration of nonribosomal organelles or
other cellular constituents.
SUMMARIO IN INTERLINGUA
Erythrocytos que contine ribosomas ha presumitemente le potential de
formar cellulas marmorate. Le ribosomas in cellulas ab animales con anemia
per phenylhydrazina o phiebotomia pote causar marmoration quando pel-
liculas de sanguine es siccate lentemente o quando illos es tincturate supra-
vitalmente con diluite concentrationes de nove blau methylenic. Le ribosomas
de cellulas ab animales con intoxication per plumbo ha un plus grande diathese
a formar aggregatos e, per consequente, a manifestar marmoration.
Viste que le formation de iste phenomeno in le cellula depende del desicca-
tion cellular, illo non occurre in cellulas suspendite in plasma, e non in cellulas
preparate routinarimente pro le microscopia electronic. Le marmorate material
basophilic producite in certe cellulas sangilinee per le action de tincturation
supravital consiste exclusivemente de ribosomas. Le association de ferro
nonhemic con le phenomeno de marmoration basophilic es usualmente le
consequentia del presentia de duo separate structuras morphologic intra le
cellulas. Iste duo structuras intracellular non pote esser resolvite, le un ab le
altere, per microscopia a lumine o de phase, sed illos pote esser distinguite
per Ic uso de un microscopio electronic.
Le occurrentia “spontanee” de marmoration basophilic pote esser inter-
pretate como evidentia de un anormalitate ribosomal, sed le multiplicitate de
lesiones cellular que es inducite per plumbo, per altere substantias chimic, per
pharmacos, o per processos pathologic, indica possibilemente que aggregation
ribosomal resulta ab le alteration de organellas nonribosomal o de altere
constituentes in le cellula.
REFERENCES
1. Ehrlich, P.: Uber einige beobachtungen 1. Milano, Societa Editrice Libraria,
am an#{228}mischen blut. Berl. Klin. 1933, p. 22.
\Vschr. 1881. 5. Brookfield, R. W.: Blood change oc-
2. Behrend: In Ucber basophile kornungen curring during the course of treat-
in rother blutkorpen by Litten, M. ment of malignant disease by lead,
Dtsch. Med. Wschr. 25:717, 1899, with special reference to punctate
and Vereins-Beilage 25:253, 1899. basophilia and the platelets. J. Path.
3. Naegeli, 0.: Blutkrankheiten und Blut- Bact. 31:277, 1928.
diagnostik. Berlin, Julius Springer, 6. Whitby, L. E. H., and Britton, C. J.1931, p. 122. C.: The relation of the stippled cell
4. Ferrata, A.: Le Emopatie, vol. 1, part and the polychromatic cell to the
For personal use only.on April 12, 2019. by guest www.bloodjournal.orgFrom
BASOPHILIC STIPPLING IN RED CELLS 943
reticulocyte. Lancet 1:1173, 1933.7. Dustin, P., Jr.: Contribution a l’#{233}tude
histophysiologique et histo chimique
des globules rouges des vert#{233}br#{233}s.
Arch. Biol. 60:285, 1943.
8. Douglas, A. S., and Dacie, J. V.: The
incidence and significance of iron
containing granules in human erythro-
cytes and their precursors. J. Clin.
Path. 6:307, 1953.
9. McFadzean, A. J. S., and Davis, L. J.:On the nature and significance of
stippling in lead poisoning, with ref-
erence to the effect of splenectomy.
Quart. J. Med. 18:57, 1949.
10. Bruckner, H.: Arbeiten #{252}ber die baso-
phile substanz in den jugendlichen
roten blutkorperchen II. Uber die
physikalischchemischen eigenschaften
der basophilen substanz in den jug-
endlichen erythrocyten. Arch. Hyg.
98:95, 1927.
11. Jensen, W. N., and N’Ioreno, C.: Les
ribosomes et les ponctuations baso-
philes des #{233}rythrocytes dans l’intox-
ication par le plomb. C. R. Acad. Sci.
(Paris) 258:3596, 1964.
12. Brecher, G.: New methylene blue as a
reticulocyte stain. Amer. J. Clin.
Path. 19:895, 1949.
13. Haeger-Aronsen, Birgitta: Studies on
urinary excretion of 8-amino-laevul-
inic acid and other haem precursors
in lead workers and lead intoxicated
rabbits. Scand. J. Clin. Lab. Invest.
(suppl.) 12:1, 1960.
14. Bessis, M., and Breton-Gorius, Janine:
Le r#{233}ticulocyte. Colorations vitales
et microscopic #{233}lectronique. Nouv.
Rev. Franc. Hemat. 4:77, 1964.
15. Beriti#{233}, T.: Siderotic granules and the
granules of punctate basophilia. Brit.
J. Haemat. 9:185, 1963.
16. Sano, S.: Studies on the nature of the
basophilic stippled cells in lead poi-
soning. Report I. Studies on the cyto-
logical investigation of hasophilic
stippled cells. Acta Haemat. Jap. 18:
625, 1955.
17. -: Studies on the nature of the l)asO-
philic stippled cells in lead poison-
ing. Report II. Studies on the mecha-
nism of granule-formation of baso-
philic stippled cells in lead pOiE)fl-
ing. Acta Haemat. Jap. 18:631, 1955.
18. Bessis, M., and Breton-Gorius, Janine:
Etude au microscope #{233}lectronique dim
sang et des organes h#{233}mopoietiques
dans le saturnisme experimental.
Path. Biol. (Scm. Hop.) 33:411,
1957.
19. Burka, E. R., and Marks, P. A.: Ribo-
somes active in protein synmthesis in
human reticulocytes: a defect in thai-
assemia major. Nature 199:706, 1963.
20. Fratianne, R. B., Griggs, R. C., and
Harris, J. W.: Autosurvival of eryth-
rocytes treated in vitro with lead
chlorides. Clin. Res. 7:384, 1958.
21. Westerman, Ni. P., and Jensen, W. N.:
Effect of lead, in vivo and in vitro
on radiophosphorus incorporation in-
to erythrocyte phosphatides. J. Clin.
Invest. 42:993, 1963.
22. Bessis, M. C.., and Breton-Gorius, J.:Iron metabolism in the bone mar-
row as seen by electron microscopy:
A critical review. Blood 19:635, 1962.23. Chisholm, J. J., Jr.: Disturbances in the
biosynthesis of heme in lead intoxi-
catiOn. J. Pediat. �: 174, 1964.
Wallace N. Jensen, M.D., Professor of Medicine, Head of
Division of Henuitolagy of the Department of Medicine of the
University of Pittsburgh Medical School, Pittsburgh, Pa.
Giuliana Moreno, B.S., Research Assistant, Centre National
de Transfusion Sanguine, Paris, France.
Marcel C. Bessis, M.D., Professor Agrege, Department of
Medicine, University of Paris, Head of Research Laboratories,
Centre National de Transfusion Sanguine, Paris, France.
For personal use only.on April 12, 2019. by guest www.bloodjournal.orgFrom
1965 25: 933-943
WALLACE N. JENSEN, GIULIANA D. MORENO and MARCEL C. BESSIS An Electron Microscopic Description of Basophilic Stippling in Red Cells
http://www.bloodjournal.org/content/25/6/933.full.htmlUpdated information and services can be found at:
Articles on similar topics can be found in the following Blood collections
http://www.bloodjournal.org/site/misc/rights.xhtml#repub_requestsInformation about reproducing this article in parts or in its entirety may be found online at:
http://www.bloodjournal.org/site/misc/rights.xhtml#reprintsInformation about ordering reprints may be found online at:
http://www.bloodjournal.org/site/subscriptions/index.xhtmlInformation about subscriptions and ASH membership may be found online at:
Copyright 2011 by The American Society of Hematology; all rights reserved.Hematology, 2021 L St, NW, Suite 900, Washington DC 20036.Blood (print ISSN 0006-4971, online ISSN 1528-0020), is published weekly by the American Society of
For personal use only.on April 12, 2019. by guest www.bloodjournal.orgFrom
top related