Pancytopenia due to iron deficiency worsened by iron infusion: a case report.

Abstract

Iron deficiency anemia is commonly associated with thrombocytosis, although thrombocytopenia has been reported in occasional patients with iron-deficiency anemia. Much less common is the development of thrombocytopenia following replenishment of iron stores.
We present the unusual case of a 39 year old African American female Jehovah's Witness who presented with a 10 month history of menorrhagia and pancytopenia. Laboratory investigations confirmed a severe iron deficiency. Since blood transfusion was unacceptable to her, she was started on intravenous iron replacement therapy. This precipitated a sudden drop in both her platelet and white blood cell counts. Histopathological examination of the bone marrow revealed a hypercellular marrow with orderly trilineage hematopoiesis, iron deficiency anemia, granulocytic hyperplasia, and mild megakaryocytic hypoplasia. Both her white blood cell and platelet counts recovered uneventfully with continuing iron supplementation. The possible mechanism for this phenomenon is discussed in this report.
This case illustrates two rather uncommon associations of a very common problem. Severe iron deficiency anemia may be associated with pancytopenia and iron replacement may cause a transient decline in megakaryopoiesis and leukopoiesis. Severe iron deficiency should be added to the list of conditions leading to thrombocytopenia.

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BioMed Central
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Journal of Medical Case Reports
Open Access
Case report
Pancytopenia due to iron deficiency worsened by iron infusion: a
case report
Apar Kishor Ganti*1,2, Nicole A Shonka3 and William D Haire1
Address: 1Department of Internal Medicine, Division of Oncology/Hematology, University of Nebraska Medical Center, Omaha, NE, USA, 2VA
Medical Center, Omaha, NE, USA and 3Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USA
Email: Apar Kishor Ganti* - aganti@unmc.edu; Nicole A Shonka - nshonka@unmc.edu; William D Haire - whaire@unmc.edu
* Corresponding author
Abstract
Introduction: Iron deficiency anemia is commonly associated with thrombocytosis, although
thrombocytopenia has been reported in occasional patients with iron-deficiency anemia. Much less
common is the development of thrombocytopenia following replenishment of iron stores.
Case Presentation: We present the unusual case of a 39 year old African American female
Jehovah's Witness who presented with a 10 month history of menorrhagia and pancytopenia.
Laboratory investigations confirmed a severe iron deficiency. Since blood transfusion was
unacceptable to her, she was started on intravenous iron replacement therapy. This precipitated a
sudden drop in both her platelet and white blood cell counts. Histopathological examination of the
bone marrow revealed a hypercellular marrow with orderly trilineage hematopoiesis, iron
deficiency anemia, granulocytic hyperplasia, and mild megakaryocytic hypoplasia. Both her white
blood cell and platelet counts recovered uneventfully with continuing iron supplementation. The
possible mechanism for this phenomenon is discussed in this report.
Conclusion: This case illustrates two rather uncommon associations of a very common problem.
Severe iron deficiency anemia may be associated with pancytopenia and iron replacement may
cause a transient decline in megakaryopoiesis and leukopoiesis. Severe iron deficiency should be
added to the list of conditions leading to thrombocytopenia.
Introduction
Iron deficiency anemia is the second most common nutri-
tional deficiency in the United States [1] with an esti-
mated 3.3 million women of child bearing age suffering
from the condition [2].
Iron deficiency anemia is commonly associated with
thrombocytosis with platelet counts between 500 to 700
× 109/L [3]. The mechanism for this increase in platelet
counts is thought to be the stimulation of platelet produc-
tion by erythropoietin that is present in moderately
increased levels in patients with iron-deficiency anemia
[4]. Thrombocytopenia, although relatively uncommon
in the setting of iron-deficiency anemia, has been reported
before [5-7]. Another little known phenomenon is the
development of thrombocytopenia following replenish-
ment of iron stores [8,9]. A mild leukopenia has been
reported with iron-deficiency anemia as well [10]. How-
ever, a decline in leukocyte counts following iron therapy
has not been reported for leukocytes.
Published: 7 December 2007
Journal of Medical Case Reports 2007, 1:175doi:10.1186/1752-1947-1-175
Received: 3 July 2007
Accepted: 7 December 2007
This article is available from: http://www.jmedicalcasereports.com/content/1/1/175
© 2007 Ganti et al; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0),
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Journal of Medical Case Reports 2007, 1:175http://www.jmedicalcasereports.com/content/1/1/175
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In this report, we present the unusual case of a severely
iron deficient patient who presented initially with pancy-
topenia and then developed a precipitous decline fol-
lowed by a recovery in platelet and leukocyte counts after
iron replacement.
Case presentation
A 39 year old African American female Jehovah's Witness
with a ten-month history of menorrhagia was admitted
for severe anemia and pancytopenia. Her hemoglobin on
admission (Hgb) was 3.1 g/dL (normal range: 11.0 – 15.1
gm/dL), mean corpuscular volume was 58.6 fL (normal
range: 79 – 97 fL) and red cell distribution width (RDW)
was 35% (normal range: 11.3 – 15.5%). Reticulocyte
count was low at 8000/mm3 (normal range: 25 – 100 ×
103/mm3), and iron studies revealed a serum iron level of
17 µg/dL (normal range: 37 – 170 µg/dL), total iron bind-
ing capacity of 447 µg/dL (normal range: 250 – 450 µg/
dL), percentage saturation of 4 and a ferritin level of <2
ng/mL (normal range: 10 – 100 ng/mL). Erythropoietin
level was elevated at 9544 mU/mL (normal range: 0 – 27
mU/mL). White blood cell (WBC) count was 2.9 × 103/µL
(normal range: 4 – 11 × 103/µL) with 46 segmented neu-
trophils, and her platelet count was 127 × 103/mcL (nor-
mal range: 150 – 400 × 103/µL), and coagulation
parameters were normal.
Given her faith, transfusion was unacceptable, and iron
supplementation was begun with intravenous iron
sucrose complex given at a dose of 100 mg twice weekly.
Two days after the initial iron infusion, her pancytopenia
worsened with a drop in her platelets to 39 × 103/mcL,
hemoglobin decreased marginally to 2.7 gm/dL, and WBC
count decreased to 1.6 × 103/mcL. Given this sudden drop
in hemoglobin, white blood cell counts and platelet
counts, a bone marrow biopsy was performed to exclude
a primary marrow disorder. Histopathological examina-
tion of the marrow revealed a hypercellular marrow, nor-
mal number of erythroid cells with a focus of left-shifted
erythropoiesis, mildly decreased number of megakaryo-
cytes. Evaluation of iron stores in the bone marrow
showed decreased amounts of storage iron, but there was
incorporation of iron. Ringed sideroblasts were not
present in the bone marrow core sections.
After ten days of iron therapy, her WBC count had nor-
malized to 5.9 × 103/mcL, hemoglobin improved to 5.2 g/
dL, and platelets were 195 × 103/mcL. She received a total
of 1500 mg of intravenous iron and at four months fol-
lowing completion of therapy, her hemoglobin (14.0 gm/
dL), platelet counts (181 × 103/mcL) and ferritin level
(121 ng/mL) were within normal limits. Her WBC count
was 3.8 × 103/mcL, slightly below the lower limits of nor-
mal (Figure 1).
Temporal profile of hemoglobin, white blood cell and platelet counts
Figure 1
Temporal profile of hemoglobin, white blood cell and platelet
counts.

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Discussion
Our patient presented with pancytopenia. Given the
extreme anemia and the marginal thrombocytopenia and
leukopenia, she was initiated on iron replacement therapy
in order to improve erythropoiesis. This led to a sudden
decline in platelet and WBC counts (Figure 1).
Although iron deficiency is associated with a reactive
thrombocytosis [3], increasing severity of the iron defi-
ciency leads to normalization [11,12] and occasionally
even decrease in platelet counts [5-7]. The exact mecha-
nism of this is unclear but may be related to the alteration
in the activity of iron dependent enzymes in thrombo-
and leukopoiesis.
The mechanism of leukopenia in our patient may be
related to the extremely high levels of erythropoietin seen
in our patient. Animal experiments and in vitro studies
using human hematopoietic stem cells have demon-
strated that addition of erythropoietin to these stem cells
down-regulates neutrophil production [13].
The sudden transient decrease in the platelet and leuko-
cyte counts following iron therapy is probably related to
the phenomenon of stem cell steal. Increased availability
of the deficient erythrocyte precursor (iron) may have led
to the diversion of the pluripotent hematopoietic stem
cells towards erythropoiesis, at the expense of the other
hematopoietic cell lines. In fact, the effect of erythropoie-
tin therapy on platelet counts has been shown to be
dependant on the adequacy of iron stores. When iron sup-
ply is inadequate, intense erythropoietin stimulation may
cause thrombocytosis, but when iron supply is available,
erythropoiesis predominates and megakaryopoiesis may
be transiently decreased [14].
Conclusion
This case illustrates two relatively uncommon findings in
an extremely common disease. Iron deficiency anemia, if
sufficiently severe, may be associated with decreased
platelet and WBC counts and iron replacement therapy
may cause a transient decline in megakaryopoiesis and
leukopoiesis.
Competing interests
The author(s) declare that they have no competing inter-
ests.
Authors' contributions
AKG conceived the study, contributed to acquisition of
data and drafted the initial manuscript and revised the
manuscript prior to submission. NAS helped with the
acquisition of the data, designing and drafting the initial
draft, and revised the draft. WDH was the clinician
responsible for making the treatment decisions on the
patient. He also made contributions to acquisition of
data, and revised the draft as necessary. All authors have
read and approved the final manuscript.
Consent
The patient was informed about the intent to publish this
report and consented to the same in writing.
Acknowledgements
There is no source of funding for this manuscript
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