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Blood, 1 June 2002, Vol. 99, No. 11, pp. 4228-4230
BRIEF REPORT
Measurement of spleen volume by ultrasound scanning in
patients with thrombocytosis: a prospective study
Marco Picardi,
Vincenzo Martinelli,
Rosanna Ciancia,
Ernesto Soscia,
Roberto Morante,
Antonio Sodano,
Giuliana Fortunato, and
Bruno Rotoli
From the Division of Hematology and Departments of
Infectious Diseases, Radiology and Laboratory Medicine, Federico II
University Medical School, Naples, Italy.
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Abstract |
Spleen size was assessed in 73 patients with thrombocytosis and in
15 healthy subjects, comparing palpation with ultrasonography (US)
measurement of longitudinal diameter and volume. Intraobserver and
interobserver variability for volume on US, checked in 12 patients, was
very low. Correlation between spleen volume measured by US and that
measured by computed tomography was excellent. Splenomegaly was
detected by palpation in 25% of patients, by US assessment of
longitudinal diameter in 33%, and by US assessment of volume in 52%.
After diagnostic work-up, 54 patients had a diagnosis of essential
thrombocythemia (ET), 4 of idiopathic myelofibrosis (IMF), and
15 of secondary thrombocytosis (ST). Spleen volume in patients
with ST was in the normal range (138 ± 47 mL) and was significantly
lower than that in patients with ET or IMF (370 ± 210 mL;
P < .001). Thus, US-measured volume was the most
sensitive method for identifying nonpalpable splenomegaly in
patients with primary myeloproliferative diseases, and it may help in
distinguishing these diseases from reactive disorders.
(Blood. 2002;99:4228-4230)
© 2002 by The American Society of Hematology.
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Introduction |
Enlargement of the spleen is an important criterion
in diagnosing primary myeloproliferative diseases.1-3
Because splenomegaly may occur in patients in whom the spleen is not
palpable, the most sensitive imaging procedure for measuring splenic
size has been sought. Nuclear medicine techniques, which are
relatively complex and not routinely available, expose patients to
radiation.4-6 One-dimensional ultrasonography (US) is
often inaccurate.7 Computed tomography (CT) and magnetic
resonance imaging are relatively expensive. Thus, stringent
criteria for defining splenomegaly by using imaging methods are still
controversial.1-7 We tested the accuracy of US-measured
spleen volume compared with palpation and US-measured longitudinal
diameter in detecting splenomegaly in patients with thrombocytosis
subsequently classified as having myeloproliferative diseases or
reactive conditions. We used a group of healthy subjects to establish
reference ranges for US volume and a patient subgroup to assess
variability in US measurements and examine the correlation between
US-measured and CT-measured spleen volume.
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Study design |
In the past 3 years, we prospectively studied 73 consecutive patients (43 women and 30 men; median age, 50 years
[range, 13-75 years]; median body-surface area, 1.7 m2 [range 1.4-2.0 m2]) who presented with thrombocytosis
(median platelet count, 720 × 109/L; range,
600-1898 × 109/L) of unknown origin. Patients with overt
spleen enlargement (ie, 3 cm from the costal border at palpation) or
with a disease associated with splenomegaly (eg, portal hypertension or
thalassemia) were excluded from the study. Informed consent to
participation was obtained from all subjects studied.
All spleen US scans were performed by the same operator, who used
an EUB 525 Hitachi (Tokyo, Japan) instrument with a 2.5/3.5-MHz broadband curvilinear probe. The spleen was scanned in patients who
were fasting, in the longitudinal and transverse planes by using an
intercostal approach, a subcostal approach, or both. The
patient was placed in a supine or right-sided position until complete
organ visualization was achieved.8-10 Perimeter,
longitudinal diameter, and area, defined as the maximum measurements
with splenic borders and angles clearly defined, were measured, and
volume (in milliliters) was calculated automatically. Reference values for volume were obtained from measurements in 15 healthy subjects matched with the patients for sex, age, and body-surface area. For each
subject, the mean value of 3 measurements repeated on the same occasion
was calculated and recorded for final analysis.
Twelve unselected patients were studied by repeated US
measurements on 2 occasions at a 1-week interval by the same operator (intraobserver reproducibility) and by another operator unaware of the
previous results, with both operators using the same US machine
(interobserver reproducibility).11,12 After informed consent to participation was obtained again, the same 12 patients underwent a CT examination. Spleen axial images were obtained by using
a multirow helical instrument (Mx 8000; Marconi Medical Systems,
Cleveland, OH), to produce a 3-dimensional model used to calculate
volumes automatically.13 Technical parameters included 6.5-mm slice width with identical reconstruction index, pitch 1, 200 mA, 120 kilovolt potential, and a rotation time of 0.75 seconds.
All patients underwent physical examination, full blood counts,
assessment of blood smears and serum ferritin levels, and a search for
possible causes of reactive thrombocytosis. Morphologic, cytogenetic,
and molecular studies of bone marrow aspirates and a trephine biopsy
with use of the Perls reaction for iron deposits and the
silver-impregnation method for grading reticulin fibrosis were
performed in all nonsecondary cases. In accordance with the updated
criteria of the Polycythemia Vera Study Group,1,2 54 patients were found to be affected by essential thrombocythemia (ET), 4 by idiopathic myelofibrosis (IMF), and 15 by secondary thrombocytosis
(ST) due to inflammatory conditions, iron-deficiency anemia,
amyloidosis, or metastasizing malignant disease.
Statistical evaluations, including  2 testing, analysis
of variance with Bonferroni correction, and Pearson correlation, were performed with SPSS for Windows software (version 9.0; SPSS,
Chicago, IL).
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Results and discussion |
Intraobserver reproducibility and interobserver reproducibility of
measurements of spleen volume by US were excellent, with Pearson values
of 0.999 and 0.997, respectively. Spleen-volume measurements by US and
by CT scanning were strongly correlated, with a Pearson value of 0.945 (P < .001).
In the healthy subjects, spleen longitudinal diameter ranged from 8 to
11 cm (median, 9.5 cm) and spleen volume from 60 to 200 mL (median, 140 mL). Among the 73 patients studied, spleen enlargement was detected by
palpation (between 0.5 and 2 cm below the costal margin) in 18, by US
assessment of longitudinal diameter in 24, and by US assessment of
volume in 38. A Pearson value of 0.407 indicated a clear disagreement
between the volume and longitudinal-diameter measurements. Measurement
of volume had significantly higher sensitivity in detecting
splenomegaly compared with measurement of longitudinal diameter and
palpation (52% versus 33% or 25%; P = .003). Of the 54 patients with ET, 16 (29%) had palpable splenomegaly, 22 (40%) had
increased longitudinal diameter on US, and 34 (63%) had volume enlargement on US (overall median, 320 mL; range, 81-1000 mL). The
difference in median spleen volume between patients with ET and healthy
subjects was significant (P < .001). All 4 patients with
IMF had marked spleen-volume enlargement (median, 670 mL; range
510-1000 mL), whereas only 2 of them had splenomegaly on palpation or
US assessment of longitudinal diameter. In the group with ST,
spleen-volume estimation by US was in the normal range (median, 110 mL).
In a preliminary analysis, we stratified the patients in the ET cohort
according to US-measured spleen volume. Twenty patients with a normal
volume ( 200 mL) had a median serum lactic dehydrogenase (LDH)
level of 350 U/L (range, 200-509 U/L; normal value, 227-450 U/L) and no
or mild bone marrow fibrosis; 18 patients with a spleen volume between
246 and 490 mL had a median LDH level of 452 U/L (range, 360-774 U/L),
with mild to moderate bone marrow fibrosis in 11; and 16 patients with
a spleen volume at least 500 mL had a median LDH level of 462 U/L
(range, 200-748 U/L), with mild to moderate bone marrow fibrosis in
14. In 2 patients in the latter group, IMF developed after a
median follow-up time of 12 months, whereas none of the patients in the
other groups had onset of IMF after a median follow-up time of 18 months. Moreover, patients with ET and a spleen volume at least 500 mL
had less response to a first-line interferon treatment; only one of the
5 patients in this group had normalization of platelet counts, compared
with 11 of 14 patients in the groups with no to moderate (< 500 mL) spleen-volume enlargement.
In conclusion, in contrast to other studies employing different
methods,5-7 we found a high rate of splenomegaly in
patients with ET by using US measurements of volume (Figure
1). These findings are consistent with
those of another series, in which spleen volume was measured by a
radionuclide technique (single-photon emission CT).4
Because the spleen is an irregularly shaped organ that may enlarge at
different rates in its various dimensions, physical examination1-3 and imaging using one-dimensional
measurements5-7 may underestimate the true organ size,
thus suggesting an erroneously low incidence of splenomegaly in
patients with ET. Multidimensional US spleen-volume measurement
(defined as the integration of longitudinal diameter, perimeter, and
area) is a rapid, reliable, and low-cost method for detecting the true
spleen size (Figure 2). In addition, our
data support the concept of clinical heterogeneity in patients with
ET3,14,15; a role for spleen-volume measurement in
subgrouping these patients will be better evaluated by studies in
progress.
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| Figure 1.
Spleen volume in healthy subjects and in patients with
thrombocytosis.
Spleen volume was measured by US in healthy control subjects (NCS) and
in patients with secondary thrombocytosis (ST), essential
thrombocythemia (ET), or idiopathic myelofibrosis (IMF).
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| Figure 2.
Various spleen shapes detected by US.
(A) Spleen in a control subject having normal longitudinal diameter and
volume. (B) Spleen in a thrombocythemic patient having longitudinal
diameter like that in Figure 2A but clearly enlarged volume. (C) Spleen
in a control subject showing enlarged longitudinal diameter but normal
volume (rodlike spleen).
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Footnotes |
Submitted November 14, 2001; accepted January 23, 2002.
The publication costs of this
article were defrayed in part by
page charge payment. Therefore,
and solely to indicate this fact,
this article is hereby marked
"advertisement"
in accordance with 18 U.S.C.
section 1734.
Reprints: Bruno Rotoli, Divisione di Ematologia, Nuovo
Policlinico, Via S Pansini 5, 80131, Naples, Italy; e-mail:
rotoli{at}unina.it.
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Abstract
Introduction