From www.bloodjournal.org by guest on June 17, 2017. For personal use only.
Tn
Polyagglutination
By P. M.
Preceding
Ness,
G. Garratty,
P. A. Morel,
Tn polyagglutination
(persistent
mixedfield polyagglutinatien)
was detected
in the
blood
of a 66-yr-old
male laborer
at the
time of a splenectemy
for life-threatening
thrombocytopenia.
Confirmation
that
the
polyagglutination
was caused
by Tn activation was established
by the use of lectins,
by failure of the patient’s
red cells to react
with sera from ether patients
with Tn polyagglutination,
by weak
aggregation
with
polybrene,
by low red cell sialic acid levels,
P
OLYAGGLUTINATION
ABO-compatible
of
sera
human
Acute
and
Leukemia
H. A. Perkins
and by the persistence
of polyagglutination
over several
years of testing.
Two years
after the discovery
of the Tn polyagglutination, the patient
developed
acute
myelomonocytic
leukemia.
Vigorous
chemotherapy regimens
resulted
in clinical remission
of the leukemia
and the Tn polyagglutination. This report describes
the first known
case of Tn polyagglutination
preceding
the
development
of acute
myelogenous
Ieukemia.
erythrocytes
agglutinate
is observed
when
the tested
red cells.
most
Unless
normal
this is
recognized
and handled
appropriately
in the blood bank,
blood grouping
and
cross-match
problems
usually
occur.
Tn polyagglutination,
or persistent
mixedfield polyagglutination,
is a type of polyagglutination
commonly
associated
with
hematologic
abnormalities,
anemia.’
It has also
change
described
his
their
blood
a patient
red
cells.2
In
development
including
been
grouping
with acute
the
case,
Tn
myelocytic
blood
donors
donations.
leukemia
a 66-yr-old
hospitalized
for
segmented
count
120
white
fever.
giant
suggested
laborer,
Initial
band
by abdominal
In 1972
109/liter)
had
blood
forms
polyagglutination
AND
hematologic
examinations
and
x-nays.
an enlarged
and
hypercellular,
was
detected
problems
revealed
first
spleen
some
atypical
He was
discharged
was
thrombocytopenia
with
detected
(56
myeloid
x
without
10 cm
hyperplasia
and
below
were
and
normal
3.1
mild
to the
a left shift
a specific
the
costal
margin.
again.
The
megakanyocytes.
count
of 2.3
M:E
From
ratio
x lOt/liter,
with
of 6:1.
Platelet
the Hematology
the Irwin
Memorial
Institutes
of Medical
Submitted
Bank
Sciences.
reprint
Francisco,
Calif
by Grune
requests
and
studies3
Fort
Miley
of the San
San
July 25. 1978; accepted
Address
1979
kinetic
Service.
Blood
polys,
44%
Blood
to P. M.
Francisco,
March
Ness,
studies
bone
revealed
hypensplenism
Veterans
Francisco
series,
with
Splenomegaly
Leukopenia
bone
marrow
was
with
Hospital,
San
x
suggested
a
he
of 43%,
normal
2.9
moderately
for splenectomy
(shortened
Society.
(WBC
was
scan
a hematocnit
marrow
Administration
Medical
58%
(platelet
in the myeloid
A liver-spleen
hypercellular
he was
with
diagnosis.
On admission
lymphadenopathy.
when
109/liten,
forms.
revealed
without
x
thnombocytopenia
erythroid
noted
in 1966
(WBC
multinucleated
109/liten)
discovered
leukopenia
hepatosplenomegaly
30
prior
METHODS
diffuse infiltrative
process, but liver biopsy was refused.
In January
1974 his platelet
count fell to 22 x lOt/liter.
©
to
In 1976
Bird
and associates
noted
to have Tn activation
of
cells, 2% bands, 36% lymphocytes,
and 4% monocytes)
x 109/liten).
Bone marrow examination
demonstrated
occasional
San
hemolytic
appeared
Report
F.G.,
and
and
who have
leukemia.
MATERIALS
Case
thrombocytopenia,
in healthy
on later
myelocytic
present
of acute
leukopenia,
detected
had
a WBC
megakaryocytes
survival,
with
San
Francisco,
Francisco,
Calif.,
rapid
Calif.,
and
the
Calif
1. 1979.
M.D..
Irwin
Memorial
Blood
Bank,
270
Masonic
Avenue,
94118.
& Stratton.
Inc.
0006-4971/79/5402-0005$01.00/O
Blood.
Vol. 54, No.
1 (July), 1979
From www.bloodjournal.org by guest on June 17, 2017. For personal use only.
Tn POLYAGGLUTINATION
splenic
31
sequestration)
and ineffective
thrombopoiesis
(low platelet turnover
rate). It was predicted
that
improve
the platelet
count, but to a subnormal
level, because
of apparent
bone
During the preoperative
investigations
he was found to have polyagglutinable
red
cells caused by Tn activation.
At surgery
the spleen weighed
860 g and was speckled
with nodules.
The liver was enlarged
but
appeared
normal. Microscopic
examination
revealed congestive
splenomegaly
with focal extramedullary
hematopoiesis
and moderate fatty metamorphosis
of the liver. Postoperatively
the platelet count rose to
143 x 10’/liter,
and in September
1974 it was 185 x l09/liter.
By December
1975 the platelet
count
splenectomy
would
marrow dysfunction.
had fallen to
WBC
count
53 x 109/liter.
43.5
In January
x 109/liter,
On readmission,
1976
the
with a marked
his bone
marrow
was
hematocnit
was
hypencellulan,
with
and reduced
megakaryocytes
with
blood and marrow
were diagnostic
atypical
multinucleated
of acute myelomonocytic
arabinoside
platelet
and
daunomycin.
The
leukemia.
He was discharged
The persistent
leukopenia
cytosine
arabinoside
and
41%,
left shift and several
count
mostly
and
febrile
platelet
and comatose
myelomonocytic
and
leukemia
myelomonoblasts
increased,
but
the
was
administered
count
died
with
on
the
fifth
widespread
were
hospital
tissue
day.
with
Despite
1976.
of
A course
in May
1976.
x l09/liter.
count of 32.6
chemotherapy,
Postmortem
peripheral
cytosine
persistent
chemotherapy
stabilized
at 70-100
An elevated
WBC
noted.
and
promyelocytes
demonstrated
in March
as consolidation
of 9 x 109/liten
20 x l09/liter,
and
marrow
with an apparent
partial remission.
improved
to 2.3 x l09/liter,
with 24% polys,
6-thioguanine
a decreased
count
red cells.
forms. The leukoenythroblastic
leukemia.
He was treated
The WBC count gradually
became normal, and the platelet count
In January
1977 he was readmitted
with increasing
fatigue.
l09/liter
platelet
nucleated
x
he became
examination
revealed
acute
infiltration.
Methods
Standard
serologic
manual.4 To measure
against serial
lectin
methods
were
the Tn activity
dilutions
anti-Tn.
The
of a normal
titration
used. Lectins were prepared
as described
in the AABB technical
on serial samples of the patient’s ned cells, the red cells were tested
group
reactions
A serum
were
as a source
expressed
of human
as agglutination
anti-Tn
and
Salvia
sclarea
as a
scones.
RESULTS
The
patient’s
Agglutination
A cells and
red
cells
were
found
to react
patient’s
saliva contained
H substance,
reacted
with all donor
sera containing
Some
donor
sera containing
anti-B
Some
AB
failed
to react
sera
react
with
reacted
(1
cells were
btfiorus,
hypogoea.
agglutinated
sg/109 RBC
Samples
studied
for
to 3+),
The
polyagglutination.
but
others
were
(normal
another
anti-Tn.
by
activity
patient’s
with
were
and
nonreactive.
anti-A,B.
with
The
All
cord
sera
cells
confirmed
of the polyagglutination,
reacted
strongly
and S. sciarea,
thus
the
with Tn polyagglutination
the patient’s
red cells
lectin.
Red
cell
sialic
demon-
to be
red
cells
were
polybrene,
acid
the
with lectins
but failed to
appeared
that
anti-A
or the Salvia
lectins.
aggregated
only weakly
by
soybean
content
failed
to
and that
the
treated
with
but
were
was
11.1
RBC).
blood from
of the
red
tests
patient
When
13-17 ig/lO9
of peripheral
Tn
was the cause
Further
they failed to react
patient’s
red cells
strongly
+
tested
with lectins.
The cells
Ulex europaeus.
S. horminum,
react
with serum
from
patient’s
serum
lacked
papain,
The
anti-B,
but no A or B substance.
The patient’s
cells
anti-A
or anti-A,B
(2+
to 3+ reactions).
reacted
I +, whereas
others
failed
to react.
the patient’s
cells.
if T or Tn activation
Arachis
Tn
anti-A,
with
To determine
patient’s
red
from Dolichos
strating
with
showed
a mixed-field
appearance.
The patient’s
serum
reacted
B cells but did not react
with 0 cells or the patient’s
own cells.
leukocytes
the patient and
and
platelets
from
a normal
by inhibiton
control were
studies
using
From www.bloodjournal.org by guest on June 17, 2017. For personal use only.
32
NESS
T able
Tn Activity
1.
of Patient’s
ET
AL.
Red Cells
Mean
Score
Agglutination
Using
Serial
Dilutions
Group A
1976
Normal
S. sclarea
Serum
66
January
9
February
7
58
March
6
60
April
5
40
May
0
16
June
0
9
July
0
6
August
0
5
November
0
0
Chemotherapy
given.
Salvia
lectin.
polyagglutination,
The
nation.
of these
red-cell-free
Details
coat
buffy
buffy
whereas
the
normal
studies
were
from
coat
reported
the patient’s
blood
did not demonstrate
elsewhere
by Beck
showed
Tn
polyaggluti-
et al.5
The Tn status of the patient’s
red cells was tested at weekly intervals
during
1976
after the diagnosis
of acute myelomonocytic
leukemia.
The cells were tested against
dilutions
of normal
group
A serum
containing
anti-Tn
and against
S. sciarea.
The
agglutination
scores
weakened
remained
considerably.
the polyagglutination
time of his death
with
elevated
Reactions
until
became
disappeared
fulminant
May
1976,
weaker
when
the polyagglutination
over the next
completely
in November
leukemia,
Tn activation
few months,
until
1976 (Table
1). At the
was not detectable.
DISCUSSION
Polyagglutinability
unexposed
or absent,
been
described:
normally
present
and
Tn.
The
bacterial
T
In vivo
infection
receptor
T activation
an acquired
in
either
membrane
receptors,
normally
de novo. Five such receptors
have
is an acquired
defect
normal
in vitro
is transient
is usually
polyagglutination
although
erythrocyte
or present
is concealed
enzymes
T polyagglutination
clears.
Tn
when
exposed
T, Tn, Cad,
Tk, and
VA.
The
corresponding
in human
adult
sera.6 The two most commonly
neuraminidase
in vivo.
ties.
occurs
become
of bone
erythrocytes
and
in contaminated
and
with
phenomenon
stem
fact that Beck et al.5 demonstrated
that our patient’s
Tn-activated
would imply a mutation
of a pluripotent
absence
of Tn activation
of buffy coat cells in other
the somatic
mutation.
We have presented
conclusive
evidence
that our
when
samples
the
abnormali-
etiology
is uncertain,
has
been
are
T
by
or
causative
hematologic
whose
cells
are
exposed
blood
disappears
not associated
marrow
antibodies
encountered
suggested.’
The
white cells and platelets
were
hematopoietic
stem cell. The
cases suggests
variable
sites of
patient
had
Tn
activation:
the
reactions
with D. biflorus,
S. sciarea,
and S. horminum
and the failure
with A. hypogoea;7
the failure
of the patient’s
cells to react with sera from
to react
another
patient
red
sialic
was
with
acid
Concurrent
reported
Tn
levels;8
activation;
and
the
the
weak
persistence
aggregation
of the
with
polybrene;
the
low
polyagglutination.
diagnosis
of acute
myelogenous
leukemia
by Bird and associates.2
Our case differs
with Tn polyagglutination
from theirs
in two important
cell
From www.bloodjournal.org by guest on June 17, 2017. For personal use only.
Tn
33
POLYAGGLUT1NATION
First, our
of acute
aspects.
diagnosis
patient
had
myelogenous
polyagglutinable
leukemia.
The
red cells for at least
Tn polyagglutination
2 yr prior to the
was discovered
by chance
when
routine
blood
grouping
was
necessary.
His long
history
of
leukopenia
and thrombocytopenia,
commonly
associated
with Tn polyagglutination,
suggests
that
his Tn activation
occurred
even
earlier.
Second,
the case
described
by
Bird
al.2
Ct
lymphadenopathy,
was
not
the inability
phosphatase
score,
and
the
more
The
typical
persistent”
after
myelogenous
of Tn
and
permanent.’2
cytotoxic
B,2
In
chemotherapy.
level
favor
Other
case,
the
diagnosis
of
case
in adults.
the
reported
The
alkaline
leukemia.9”#{176} Our
is controversial.
Bird’s
leukemia.
the low leukocyte
myelogenous
leukemia
polyagglutination
myelogenous
marrow,
vitamin
chronic
of acute
duration
acute
bone
elevated
Philadelphia-chromosome-negative
was
classic
to aspirate
It has
Tn
cases
activation
have
been
called
both
5 mo
disappeared
shown
variable
effects
of
chemotherapy.6”3”4
Our patient
lost Tn polyagglutination
concomitant
with cytotoxic
chemotherapy.
These
observations
imply
that
the Tn disappeared
as a
chemotherapy
effect,
and they further
support
the description
of Tn polyagglutination
as persistent,
not permanent.
Retrospective
analyses
of acute
myelogenous
tion of a constellation
of hematologic
findings
later. These
lar marrow.’5
ties between
activation
activation
marker.
The
development
Tn polyagglutination
develop leukemia;
resulting
have led to the recogniwho develop
leukemia
preleukemia
findings
commonly
include
pancytopenia
with hypercelluIn retrospect,
our patient
had a preleukemic
syndrome.
The similarithe preleukemic
syndrome
and the hematologic
findings
with
Tn
suggest
a possible
relationship.
may also have been responsible
kemic
leukemia
in patients
from
The
for
of acute
somatic
cell mutation
causing
the Tn
his preleukemic
state
or a preleu-
myelogenous
leukemia
may be analogous
to the situation
both disorders are marked
by
proposed
somatic
cell
mutation
in patients
in patients
with
red cell membrane
and
often
resulting
with
PNH
who
defects
in hemolytic
anemia
and various
cytopenias.’6
Several
observations
detract
from this attractive
hypothesis:
(1) we do not know if the Tn activation
occurred
concurrently
with his
hematologic
problems;
(2) the Tn disappeared
when
the leukemia
relapsed;
(3)
many other patients with Tn activation
have
not developed
leukemia.
Despite
the fact that we cannot
prove that the Tn activation
had any etiologic
of acute
role in his development
acute leukemia
of any
patient
in this
case
or blood
myelogenous
and
donor
one
with
other
leukemia,
case
the
association
of Tn
and
careful clinical observation
justifies
Tn polyagglutination.
ACKNOWLEDGMENT
We
wish
to thank
buffy
Malcolm
testing
the
coat
Texas,
for determinations
Beck,
preparations
F.I.M.L.S.,
for Tn
of red cell
sialic
Community
activation
acid
and
BlOOd
Dr.
Center,
Kansas
E. A. Steane,
Pankland
City,
Kansas,
Hospital,
for
Dallas,
levels.
REFERENCES
1. Bind
Persistent
Haematol
2.
iG,
cation
GWG,
Shinton
mixed-field
21:433,
Bird
Melikian
in
GWG,
Wingham
i:
Br
J
1971
i, Pippard
Erythrocyte
malignant
lymphoreticulan
acute
diseases
Mi,
membrane
of
myeloid
Hoult
modifi-
and
3.
tissue.
myelocyte
33:289,
Wingham
V:
NR,
polyagglutination.
I. Tn-polyagglutination
leukaemia.
Br
i
in
Haematol
1976
Ries
CA,
Price
thrombocytopenia.
4. Miller
DC:
Ann
WV
(ed):
5’Cr
Intern
American
platelet
Med
kinetics
80:702,
Association
in
1974
of
From www.bloodjournal.org by guest on June 17, 2017. For personal use only.
ET AL.
NESS
34
Blood
Banks
phia,
Technical
Lippincott,
5.
Beck
ML,
cases
34:325,
BL,
Pierce
Philadel-
on leucocytes
SR,
and
of Tn-polyagglutination.
Issitt
Serology
tent
(ed
7.
Issitt
platelets
Lab
2).
Bird
GWG,
Salvia.
in
Sci
Oxnard,
Applied
Calif,
Spectra
Dickinson,
Wingham
Vox
BlOOd
Sang
Group
Hematol
and
AA:
negative
Intern
11.
Pinkola
12:409,
DZ,
Ezdinli
Sandberg
12.
Biologi-
1975
i:
Haemagglutina-
26:163,
1974
Ci:
Med
Cnosswhite
Philadelphia-chromosome
chronic
72:175,
Myllyla
A, Tippet
G,
BS,
leukemia.
Ann
1970
Furnhjelm
P. Gaving
U,
10:7,
Nondling
R: Persis-
5,
DT,
mixed
field
Taswell
HF,
I. Serological
polyagglutina-
observations.
Vox
13. Haynes
CR,
Dorner
I, Leonard
Anrowsmith
WR, Chaplin
H in: Persistent
GL,
poly-
agglutinability
acti-
14.
in vivo
Transfusion
iiii
at
American
unrelated
10:43,
RM,
presented
iahn
the
Miami
Saarni,
hematologic
16. Rosse
Bilenki
annual
of
Beach,
MI,
to T-antigen
1970
EFW,
26th
Association
Harbour,
syndrome
Blood
Fla,
Linman
LA:
meeting
Paper
of
Banks,
the
Bal
1973
iW:
preceding
Pneleukemia,
acute
the
leukemia.
1973
Paroxysmal
nocturnal
hemoWi, Burton E, Erslev Al,
Rundles
RW
(eds):
Hematology
(ed 2). New
York, McGraw-Hill,
1977, p 560
globinunia,
i, Sangen
Sang
1973
Am i Med 55:38,
positive
myelocytic
Vox
P. McQuistan
(PMFP).
15.
HE,
Electroki-
aspects.
Permanent
25:481,
vation.
1975
Sokal
polyagglutinability:
serological
Sturgeon
Allen
Sang
8. Dahr W, Uhlenbnuck
G, Bird GWG: Cryptic A-like
receptor
sites
in human
erythrocyte
glycoproteins:
Proposed
value of Tn-antigen.
Vox
Sang 27:29, 1974
9. Laszlo
i: Myeloproliferative
disorders.
10.
and
1971
Edwards
Med
CH:
of Becton,
from
Semin
mixed-field
bility
PD,
Division
tions
7).
1977
6.
cals,
(ed
netic
Hicklin
RL: Observations
six
Manual
1977
WF:
in Williams
From www.bloodjournal.org by guest on June 17, 2017. For personal use only.
1979 54: 30-34
Tn polyagglutination preceding acute leukemia
PM Ness, G Garratty, PA Morel and HA Perkins
Updated information and services can be found at:
http://www.bloodjournal.org/content/54/1/30.full.html
Articles on similar topics can be found in the following Blood collections
Information about reproducing this article in parts or in its entirety may be found online at:
http://www.bloodjournal.org/site/misc/rights.xhtml#repub_requests
Information about ordering reprints may be found online at:
http://www.bloodjournal.org/site/misc/rights.xhtml#reprints
Information about subscriptions and ASH membership may be found online at:
http://www.bloodjournal.org/site/subscriptions/index.xhtml
Blood (print ISSN 0006-4971, online ISSN 1528-0020), is published weekly by the American Society of
Hematology, 2021 L St, NW, Suite 900, Washington DC 20036.
Copyright 2011 by The American Society of Hematology; all rights reserved.