A Bone marrow biopsy technique suitable for use in neonates

ArticleinBritish Journal of Haematology 107(2):458-60 · December 1999with8 Reads
Impact Factor: 4.71 · DOI: 10.1046/j.1365-2141.1999.01712.x · Source: PubMed
Abstract

Thrombocytopenia and neutropenia are common among neonates in intensive care units. Bone marrow aspirations are sometimes performed as part of their evaluation. However, marrow biopsies have not been reported from living neonates. Since architecture and cellularity cannot generally be accurately assessed from marrow aspirates, we devised a biopsy technique which we successfully applied to five cytopenic neonates (three with severe persistent thrombocytopenia and two with idiopathic neutropenia). This technique used a 19 gauge, half-inch Osgood needle to obtain bone marrow clots from the tibias of small preterm neonates which enabled the assessment of marrow cellularity and architecture. On the basis of our initial experience we have ceased using the traditional bone marrow aspiration technique in neonates and now use this technique exclusively.

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SHORT REPORT
A bone marrow biopsy technique suitable for use in neonates
MARTHA C. SOLA,LISA M. RIMSZA AND ROBERT D. CHRISTENSEN Division of Neonatology, Department of Pediatrics,
and Division of Hematopathology, Department of Pathology, University of Florida College of Medicine,
Gainesville, Florida, U.S.A.
Received 2 June 1999; accepted for publication 2 August 1999
Summary. Thrombocytopenia and neutropenia are common
among neonates in intensive care units. Bone marrow
aspirations are sometimes performed as part of their evalu-
ation. However, marrow biopsies have not been reported from
living neonates. Since architecture and cellularity cannot
generally be accurately assessed from marrow aspirates, we
devised a biopsy technique which we successfully applied
to ®ve cytopenic neonates (three with severe persistent
thrombocytopenia and two with idiopathic neutropenia).
This technique used a 19 gauge, half-inch Osgood needle
to obtain bone marrow clots from the tibias of small preterm
neonates which enabled the assessment of marrow cellular-
ity and architecture. On the basis of our initial experience
we have ceased using the traditional bone marrow aspira-
tion technique in neonates and now use this technique
exclusively.
Keywords: newborn infant, marrow, biopsy.
Aspiration of cells from a neonate's bone marrow will
sometimes provide important information that is not other-
wise available (Christensen & Rothstein, 1980; Al-Mulla &
Christensen, 1995). Unfortunately, marrow aspirates obtained
from neonates, particularly small preterm neonates, are often
highly diluted with peripheral blood, and this dilution can
lead to misinterpretation. In adult patients, bone marrow
biopsies or marrow clot sections are routinely studied to
avoid this pitfall (Foucar, 1995), but no information is avail-
able regarding their use in neonates. A Jamshidi-type needle
is commonly used for bone marrow biopsies in adults and
older children ( Jamshidi & Swain, 1971). However, the
smallest such needle available is a 6-inch, 14-gauge, and
instructions call for its introduction 2±2´5 cm into the bone,
making this approach impractical for neonates. As a solution
to this problem we devised a method for obtaining marrow
clot sections in neonates which contain bone spicules with
preserved marrow architecture. This method produced
extremely small but high-quality specimens and required no
more time, or apparent patient discomfort, than a traditional
bone marrow aspirate.
MATERIALS AND METHODS
An Osgood needle (19 gauge, half-inch, Popper and Sons,
New Hyde Park, N.Y.) was introduced into the marrow space
through the anaesthetized (1% lidocaine) periosteum of the
¯at surface of the tibia, approximately 2 cm below the tibial
tuberosity. Once the operator felt, by the ®rmness of the
needle position, that the needle had penetrated into the tibia,
the trocar was completely withdrawn, and the (hollow)
needle was advanced, by twisting, into the marrow space an
additional 2±3 mm (advancing the hollow needle trephi-
nates marrow spicules into the needle). An empty sterile 3 ml
syringe (without a lure-lock) was then attached to the needle
hub and suction was applied for a few seconds, until the
®rst sign of marrow (about 50 ml) entered the syringe hub.
The syringe and the attached needle were then withdrawn
from the tibia. The marrow specimen within the needle was
withdrawn into the syringe, and the small drop allowed to
clot within the hub of the syringe. The clot was subsequently
gently dislodged and removed from the hub using the tip of a
needle, placed into a ®xative solution, processed, sectioned,
and stained in a manner identical to a typical bone marrow
biopsy, except that decalci®cation was not required.
RESULTS
Specimens obtained with this technique were used to evalu-
ate ®ve cytopenic neonates in the Intensive Care Nurseries of
Shands Children's Hospital at the University of Florida
between December 1997 and February 1999. The infants
ranged from 26 to 37 weeks gestational age, and from 9 to
135 d of life at the time of the procedure (Table I). The
procedure was performed to aid in the evaluation of severe
persistent unexplained neutropenia in two patients and
severe persistent unexplained thrombocytopenia in three.
British Journal of Haematology, 1999, 107, 458±460
458 q 1999 Blackwell Science Ltd
Correspondence: Dr Robert D. Christensen, P.O. Box 100296,
Gainesville, FL 32610-0296, U.S.A. e-mail: chrisrd@peds.u¯.edu
Page 1
The morphologic ®ndings are described in Table I and a
representative section of a specimen is shown in Fig 1. All
had abundant marrow spicules.
No adverse effects of the procedure were observed, and the
level of apparent discomfort was generally con®ned to the
placement of the local anaesthetic, after which most patients
did not grimace or cry during the remainder of the proce-
dure. In two of the thrombocytopenic patients (patients 1
and 2, Table I) the persistent thrombocytopenia was initially
thought to be secondary to decreased platelet production,
associated with the use of ganciclovir in one, and with the
presence of other congenital anomalies in the other infant.
However, in both cases the bone marrow showed normal
cellularity with increased numbers of megakaryocytes, which
prompted the physicians to further evaluate for consumptive
platelet disorders.
In some of our initial attempts to obtain trephine marrow
biopsies from preterm neonates (not shown in the table) the
trocar was removed before the needle had penetrated into the
marrow space, and consequently a trephine biopsy of bone,
but not bone marrow, was obtained. By taking care to have
the needle ®rmly inserted into the bone before removing
459Short Report
q 1999 Blackwell Science Ltd, British Journal of Haematology 107: 458±460
Table I. Five preterm neonates in the intensive care unit on whom tibial marrow clot sections were used to evaluate cytopenias.
Gestational Age at
age biopsy
Patient (weeks) (d) Indication for marrow study Marrow ®ndings
1 27 135 Persistent thrombocytopenia Normal cellularity; increased megakaryocytes
2 30 46 Persistent thrombocytopenia Normal cellularity; increased megakaryocytes
3 28 50 Persistent neutropenia Normal cellularity; myeloid left shift, with decreased segmented forms
4 37 48 Persistent neutropenia Normal cellularity; normal myeloid precursors, with complete maturation
5 26 9 Persistent thrombocytopenia Normal cellularity; normal megakaryocytes
Fig 1. Haematoxylin±eosin-stained marrow clot section (´ 200) obtained from a persistently neutropenic neonate (patient 4). The specimen
shows normal cellularity for age and complete myeloid maturation. Megakaryocytes are easily identi®ed and quantitatively normal.
Page 2
the trocar and advancing the hollow needle, we have
subsequently avoided this problem.
DISCUSSION
Cytopenias are common among neonates who require
intensive care. More than 20% of neonates admitted to
intensive care units develop thrombocytopenia (Castle et al,
1984) and 5±8% develop neutropenia (Al-Mulla & Chris-
tensen, 1995) at some time prior to hospital discharge.
Often, cytopenic neonates are managed without bone marrow
studies. However, in certain cases these studies can be useful,
and in such cases marrow aspirates have generally been used
(Rothstein, 1993; Alter & Young, 1998). The limitations
inherent in these aspirates, such as the poor re¯ection of
marrow cellularity, and the inaccuracy in quantifying the
relatively rare marrow cells, such as megakaryocytes, were
previously accepted as unavoidable.
Trephine needle biopsies have proved useful for marrow
studies of non-living human fetuses. Weber et al (1997) used
needle biopsies to obtain post-mortem specimens of human
fetal cartilage and bone, but did not report this usage on
living neonates. de-Alarcon & Graeve (1996) successfully
performed needle biopsies on femurs of aborted fetuses of
12±21 weeks gestation, but on living neonates they reported
only marrow aspirates.
One possible reason that the use of marrow biopsies or clot
sections has not previously been reported in living human
neonates is lack of a suitable technique. Perhaps another
reason is a perceived higher level of discomfort to the patient
with a biopsy than with an aspirate. However, after per-
forming ®ve successful procedures on cytopenic neonates,
using this new method, we see no greater risk of this
technique than that of a traditional aspirate, and the time of
performance and the level of patient discomfort appeared
similar. The selection of the tibia as the biopsy site for
neonates offers several advantages over the iliac crest. Even
in the smallest premature babies the tibia can be easily
positioned without disturbing the infant (usually maintained
in the supine position while on mechanical ventilation), and
it can be adequately stabilized and supported by the hand of
the physician performing the procedure. In addition, we
think that it is a safer site in very small preterm infants, since
it avoids any proximity to vital organs.
For evaluating marrow cellularity (Foucar, 1995), or for
evaluating number of megakaryocytes (Foucar, 1995;
Ichikawa et al, 1996), marrow clot sections provide all the
information that would be obtained from a biopsy, as they
generate a specimen containing abundant marrow spicules
from which cellularity and megakaryocyte concentration
can be assessed with much greater con®dence than from a
marrow aspirate. The ability to assess bone marrow cellularity
should be particularly useful in the evaluation of patients with
hypoplastic states or in®ltrated bone marrows. On the basis of
the present experience, we have ceased using the traditional
bone marrow aspiration technique when a marrow study is
deemed necessary in a neonate, and we now use this
technique exclusively.
ACKNOWLEDGMENTS
This work was supported by grants HL-44951 and RR-
00083 from the United States Public Health Service and
a Fellowship Training Grant from the American Heart
Association.
REFERENCES
Al-Mulla, Z.S. & Christensen, R.D. (1995) Neutropenia in the
neonate. Clinics in Perinatology, 22, 711±739.
Alter, B.P. & Young, N.S. (1998) The bone marrow failure
syndromes. Nathan and Oski's Hematology of Infancy and Childhood,
5th edn (ed. by D. G. Nathan and S. H. Orkin), pp. 259±286.
Saunders, Philadelphia.
Castle, V., Andrew, M., Kelton, J., Giron, D., Johnston, M. & Carter, C.
(1984) Frequency and mechanism of neonatal thrombocyto-
penia. Journal of Pediatrics, 108, 749±755.
Christensen, R.D. & Rothstein, G. (1980) Exhaustion of mature
marrow neutrophils in neonates with sepsis. Journal of Pediatrics,
96, 316±329.
de-Alarcon, P.A. & Graeve, J.L. (1996) Analysis of megakaryocyte
ploidy in fetal bone marrow biopsies using a new adaptation of
the Feulgen technique to measure DNA content and estimate
megakaryocyte ploidy from biopsy specimens. Pediatric Research,
39, 166±170.
Foucar, K. (1995) Bone Marrow Pathology. ASCP Press, Chicago.
Ichikawa, N., Ishida, F., Shimodaira, S., Tahara, T., Kato, T. & Kitano,
K. (1996) Regulation of serum thrombopoietin levels by platelets
and megakaryocytes in patients with aplastic anaemia and idio-
pathic thrombocytopenic purpura. Thrombosis and Haemostasis,
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Jamshidi, K. & Swaim, W.E. (1971) Bone marrow biopsy with
unaltered architecture: a new biopsy devise. Journal of Laboratory
and Clinical Medicine, 77, 335±342.
Rothstein, G. (1993) Origin and development of the blood and blood-
forming tissues. Wintrobe's Clinical Hematology, 9th edn (ed. by G.
R. Lee et al), pp. 41±78. Lea & Febiger, Philadelphia.
Weber, M., Johannisson, R., Bolte, M., Ngo, T.K. & Heller, K.H.
(1997) Fine needle tissue aspiration for accurate localization of
histological specimens from complex structures. Biotechnology and
Histochemistry, 72, 243±248.
460 Short Report
q 1999 Blackwell Science Ltd, British Journal of Haematology 107: 458±460
Page 3
    • "The iliac crest is the most frequent BM sampling site in children. In newborns and neonates, conventional BM biopsies may be difficult to perform, so alternative techniques, such as obtaining marrow clot sections, can be successfully utilized [17, 18]. The BM particles in clot sections contain preserved marrow architecture, so that they provide information on the overall BM cellularity and the number and morphology of megakaryocytes . "
    [Show abstract] [Hide abstract] ABSTRACT: Due to the immaturity of the hematopoietic system at birth and different oxygenation and immune response needs of the growing organism, the bone marrow composition at birth and early infancy differs as compared to older children and adults. These age-related differences, while generally recognized, are not well known to the world of hematopathology. The purpose of this article is to address the current limitation of the literature by reviewing the bone marrow ontology, its composition at birth, and the changes occurring during early infancy, and to compare these findings to adults. The review also provides a useful framework for bone marrow examination in children.
    Preview · Article · Jun 2013 · International journal of laboratory hematology
    • "However, there are little available data on that topic. In infants younger than 1 year, the tibia is sampled, and the procedure is done under general anesthesia [4, 40]. The BMBA from the posterior iliac crest typically takes approximately 10–30 min, and the patient is usually released home after an additional hour of observation to exclude any immediate local complications. "
    [Show abstract] [Hide abstract] ABSTRACT: Examination of the bone marrow biopsy and aspirate allows diagnosis and assessment of various conditions such as primary hematologic and metastatic neoplasms, as well as nonmalignant disorders. Despite being performed for many years, according to many different protocols, the procedure still remains painful for the majority of patients. This paper summarizes the current knowledge of pain reduction measures in the bone marrow biopsy and aspiration.
    Preview · Article · Dec 2012 · Annals of Hematology
  • [Show abstract] [Hide abstract] ABSTRACT: Thrombocytopenia is a very frequent problem among sick neonates, affecting up to 35% of all infants admitted to the NICU. Although multiple clinical conditions have been causally associated with neonatal thrombocytopenia, the cause of the thrombocytopenia is unclear in up to 60% of affected neonates. This article provides neonatologists with a practical approach to the thrombocytopenic neonate, with an emphasis on conditions that could be life-threatening or could have significant implications for further pregnancies. An overview of the current therapeutic modalities is also presented, including a discussion of the possible use of recombinant thrombopoietic cytokines to treat certain groups of thrombocytopenic neonates.
    No preview · Article · Oct 2000 · Clinics in Perinatology
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