Hematology
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Platelet levels before and after iron replacement therapy
in patients with iron deficiency anemia
Giampaolo Talamo, Oluwagbemiga Oyeleye, Asmita Paudel, Hamnah
Tayyab, Muneer Khan, Marcelle G. Meseeha & Ghanshyam Bhatta
To cite this article: Giampaolo Talamo, Oluwagbemiga Oyeleye, Asmita Paudel, Hamnah
Tayyab, Muneer Khan, Marcelle G. Meseeha & Ghanshyam Bhatta (2025) Platelet levels before
and after iron replacement therapy in patients with iron deficiency anemia, Hematology, 30:1,
2458358, DOI: 10.1080/16078454.2025.2458358
To link to this article: https://doi.org/10.1080/16078454.2025.2458358
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HEMATOLOGY
2025, VOL. 30, NO. 1, 2458358
https://doi.org/10.1080/16078454.2025.2458358
Platelet levels before and after iron replacement therapy in patients with iron
deficiency anemia
Giampaolo Talamo a, Oluwagbemiga Oyeleyeb, Asmita Paudelb, Hamnah Tayyabb, Muneer Khana,
Marcelle G. Meseehaa and Ghanshyam Bhattab
a
Hematology/Oncology, Guthrie Robert Packer Hospital, Sayre, PA, USA; bInternal Medicine, Guthrie Robert Packer Hospital, Sayre, PA,
USA
ABSTRACT ARTICLE HISTORY
Background: Iron deficiency anemia (IDA) is the most common cause of anemia worldwide. Received 6 October 2024
Patients with IDA often present thrombocytosis, but little is known about its degree and Accepted 21 January 2025
prevalence, and its response to iron replacement.
KEYWORDS
Methods: We conducted a retrospective review of 76 consecutive patients with anemia Iron deficiency; microcytic
secondary only to iron deficiency. Laboratory data were collected both at baseline and at 3 anemia; thrombocytosis;
months after either oral or intravenous iron replacement therapy. We defined thrombocytosis platelet response; iron
as a platelet count >400 × 109/L. replacement therapy
Results: The median age of the patients was 54 years (range, 22–90 years), and 59 of 76 (78%)
patients were females. The replacement therapy consisted of oral iron (n = 13), intravenous
iron (n = 33), or both (n = 30). The median Hb and ferritin levels at baseline and at 3 months
after the iron replacement were 9.9 g/dL and 18 mg/dL, and 12.4 g/dL (p < 0.0001) and 113
mg/dL (p < 0.0001), respectively. Thrombocytosis before and after the iron administration was
present in 17 (22%) and 4 (5%) patients, respectively. Regardless of thrombocytosis, the
platelet count decreased in 55 (72%) patients. The median platelet level at baseline and at 3
months after the iron replacement was 299 (95% CI, 276–330) and 265 (95% CI, 245–295) ×
109/L (p < 0.0001), respectively.
Conclusion: Thrombocytosis is found in about one fifth of patients with IDA at baseline, and it is
expected to resolve within 3 months of iron replacement therapy in most of them. Iron
administration is associated with a decrease of the platelet counts, even in the absence of
preexisting thrombocytosis.
Plain language summary Introduction
Iron deficiency anemia (IDA) is the most common IDA is the most common cause of anemia worldwide,
cause of anemia. Due to mechanisms that have not comprising over 60% of the anemia cases [1]. Its
been fully elucidated, patients with IDA often present most common causes are chronic blood losses (e.g.
with reactive thrombocytosis. We have conducted a gastrointestinal bleeding, heavy menstruation),
retrospective analysis of the incidence, degree, and increased requirements (e.g. pregnancy), vegetarian
duration of the elevated platelet counts in 76 consecu diet, and poor gastrointestinal (GI) absorption (e.g. bar
tive patients with anemia purely secondary to iron iatric surgery, and chronic use of a proton pump inhibi
deficiency, and we evaluated their response to iron tor [PPI]) [2]. The presence of reactive thrombocytosis
replacement therapy. We found that thrombocytosis, in patients with IDA is a long-recognized hematologic
as defined by a platelet count greater than 400 × phenomenon [3]. Its pathophysiology has not been
109/L of blood, is present in about one-fifth (22%) of fully elucidated, and several mechanisms have been
patients with IDA, and it is of moderate degree, proposed. A study of patients with IDA with and
because it never exceeded 1000 × 109/L. We also without thrombocytosis found that platelet generation
found that IDA-associated thrombocytosis resolved in is triggered by cytokines like thrombopoietin and IL-6
most patients within three months of iron supplemen [4]. Two reports demonstrated an increased megakar
tation. Interestingly, the administration of iron was yocytic count in the bone marrow of patients with
associated with a decrease of the platelet counts in IDA [5,6]. It has been proposed that the increased
most cases, even in those without thrombocytosis at platelets levels in IDA can be explained by the amino
baseline. acid sequence homology of erythropoietin and
© 2025 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrest
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Accepted Manuscript in a repository by the author(s) or with their consent.
2 G. TALAMO ET AL.
thrombopoietin [7], but this mechanism has not been guidelines, but they were decided in each case by
confirmed [8], and further investigation of this topic is the clinical judgement of the treating physician.
needed. In evolutionary terms, we can speculate that The statistical analysis was performed with the
the increased platelet production in IDA has the Minitab statistical software (Minitab, LLC, 2021. Avail
purpose to enhance primary hemostasis and counter able at: https://www.minitab.com). We compared the
act chronic bleeding. pre- and post-iron hematologic data by using two-
The treatment of IDA is iron repletion with oral and/ tailed paired samples t-tests, and the Wilcoxon
or intravenous (IV) iron formulations. The oral route is signed-rank test as nonparametric alternative, with a
the typical therapeutic approach in most patients, significant p level set at <0.05.
but IV iron is often given when poor response to oral This study received Ethics Approval by the Insti
iron is anticipated, or a more reliable hematologic tutional Review Board of our hospital (GC IRB) (IRB#
response is required. Previous studies have shown 2309-63). The GC IRB is registered with the Department
that iron replacement therapy can lower platelet of Health and Human Services, operates under the
count and correct reactive thrombocytosis in guidelines of Office of Human Research Protection
different contexts of IDA, like inflammatory bowel (OHRP), and complies with Federal Regulations
disease [9], chronic kidney disease (CKD) [10], and pre 45CFR46.
menopausal women [11]. We conducted a retrospec
tive study of 76 consecutive patients with pure iron
deficiency, i.e. in the absence of other causes of Results
anemia (e.g. CKD, bone marrow aplasia, hemolytic pro The median age of the patients was 54 years (range,
cesses, or cancer), or other conditions that could have 22–90 years), and 59 of 76 (78%) patients were
increased the platelet levels (e.g. inflammatory or auto females. Twenty-six females (44%) had menses. The
immune diseases). We analyzed the frequency and causes of IDA could be distinguished in 4 groups: (a)
degree of thrombocytosis in IDA before and after blood losses (n = 31), from the GI tract (n = 18) or
iron administration. The rationale of the study was to heavy menses (n = 13); (b) pregnancy (n = 6); (c) poor
clarify the platelet response to iron replacement: GI absorption (n = 23), from bariatric surgery (n = 12)
while thrombocytosis in the setting of IDA is a well- or chronic use of a PPI (n = 11); and (d) undetermined
known finding, the exact change in platelet counts (n = 16). Data regarding type of diet – regular vs veg
after iron supplementation has not been described in etarian – were not available. The median total iron
the medical literature. deficit, calculated according to the Ganzoni equation,
was 1006 mg (range, 473–2919 mg). The replacement
Materials and methods therapy consisted of: (a) only oral iron (n = 13), given
as iron sulfate (n = 11) or iron gluconate (n = 2); (b)
We reviewed the medical records of adult patients with only IV iron (n = 33), given as iron dextran (n = 20) or
IDA who received either oral or parenteral iron in our iron sucrose (n = 9), ferumoxytol (n = 3), or sodium
Hematology/Oncology clinic between January 2022 ferric gluconate complex (n = 1); or (c) a combination
and December 2023. We identified 76 patients in of both oral and IV iron (n = 30). Thirty-seven of the
which laboratory data of CBC and iron studies were 63 (59%) patients treated with IV iron received a
available both at baseline (i.e. obtained within 4 fixed dose of 1000 mg of iron dextran, while the rest
weeks before the administration of iron), and at 3 received various doses of IV iron (range, 125–
months (plus or minus 2 weeks) after starting the 2000 mg), at the discretion of the treating physician.
iron replacement therapy. Iron deficiency was Table 1 shows the main hematologic parameters of
defined as the presence of a serum ferritin level the 76 patients with IDA before and after the iron
<30 ng/mL, or serum ferritin 30–200 ng/mL with a
transferrin saturation <20%, regardless of the Hb
Table 1. Changes of hematologic parameters upon iron
level. The iron deficit was calculated according to the
repletion in 76 patients with IDA.
Ganzoni equation [12]: total iron deficit [mg] = body Parameter (normal Pre iron Post iron
weight [Kg] × (target Hb-actual Hb) [g/dL] × 2.4 + range in our laboratory) Median (range) Median (range) p value
depot iron [mg], using a target Hb of 12 g/dL for Hb (11.2–15.7 g/dL) 9.9 (4.0–12.4) 12.4 (7.0–16.5) <0.0001
females and 13 g/dL for males. Thrombocytosis was MCV (79.4–94.8 fL) 82.4 (56.4–103.1) 88.3 (59.1–105.5) <0.0001
RDW (11.7–14.4%) 17.1 (12.4–25.0) 15.9 (12.7–27.0) 0.033
defined as a platelet level >400 × 109/L of blood. WBCs (4–10 × 109/L) 7.0 (3.4–15.0) 6.9 (2.6–15.6) 0.64
Patients with anemia and other concurrent hematolo Platelets (182–369 × 109/L) 299 (122–815) 265 (136–735) <0.0001
MPV (9.4–12.3 fL) 9.9 (8.3–12.9) 10.0 (8.3–13.0) 0.24
gic conditions besides iron deficiency (e.g. B12 Ferritin (30–150 ng/mL) 18 (1.8–133) 113 (6.7–752) <0.0001
deficiency, folate deficiency, HIV infection, active Transferrin saturation 7.8 (3–44) 24.8 (3–72) <0.0001
(20–50%)
cancer, etc.). were excluded. Pregnant patients were
Note: Hb = Hemoglobin; MCV = Mean Corpuscular Volume; MPV = Mean
included. Dose and route of the iron replacement Platelet Volume; RDW = Red Cell Distribution Width; WBC = White
therapy did not follow established institutional Blood Cells.
HEMATOLOGY 3
replacement therapy. As expected, iron replacement
therapy led to an increase of the Hb (Figure 1(A)),
and ferritin levels (Figure 1(B)), along with increase of
transferrin saturation and MCV. We did not observe
statistically significant variations of WBC and RDW.
Thrombocytosis at baseline and 3 months after the
iron administration was found in 17 (22%) and 4 (5%)
patients, respectively. Upon review of the past
medical history, we found that 2 of those 4 patients
with persistent thrombocytosis after the iron adminis
tration had a post-traumatic splenectomy in the
remote past. The iron administration led to a reduction
of the platelet count even in those patients with plate
lets in the normal range at baseline (Figure 1(C)). When
compared to their pre-iron levels, the absolute number
of platelets decreased, by various degrees, in 55 (72%)
patients, but never below the normal range. In 21 of 76
(28%) patients, there was a numerical increase of the
platelet count after iron replacement, with a median
of 28 × 109/L (range, 2–67). In the whole group of 76
patients, the median platelet count at baseline and
at 3 months after the iron replacement was 299 (95%
CI, 276–330) and 265 (95% CI, 245–295) × 109/L (p <
0.0001), respectively, with a mean difference in platelet
count of −34 × 109/L (95% CI, −23 to −58) (Figure 1(C)).
Discussion
In our series of 76 patients with IDA, we found, as
expected, that Hb, ferritin, and transferrin saturation
levels significantly improved 3 months after the
administration of parenteral iron. Since microcytosis
is a classic feature of iron deficiency anemia, the
increase of the MVC and the corresponding decrease
of the RDW were also expected finding. In many
patients, the RDW did not normalize, and its median
remained slightly elevated. This is possibly due to the
short follow-up of our cohort, because it may take
more than 3 months for this hematologic parameter
to correct (personal observation of the authors – data
not shown). We decided to assess the response of
the anemia at about 3 months, because this is con
sidered an adequate period for the RBC synthesis:
according to some studies, the Hb increases by 0.5–
1 g/dL per week after starting iron replacement
therapy [13].
We observed the presence of thrombocytosis at
baseline in about one fifth (22%) of patients with
IDA. Its degree was moderate in all cases, and it
never exceeded 1000 x109/L, as in most cases of reac
tive thrombocytosis. While we found definite corre
lation with IDA, the magnitude of the changes in
most cases were small and not clinically relevant. Inter
estingly, platelet counts decreased after the adminis
tration of iron in most patients (72%), even in those Figure 1. Box plots of hemoglobin (A), ferritin (B), and platelet
who had at baseline a platelet level within the levels (C) before and after iron replacement therapy in 76
normal range. Only 4 of 17 patients with patients with IDA.
4 G. TALAMO ET AL.
thrombocytosis at baseline continued to have elevated baseline in most IDA patients, even in the absence of
platelets after iron replacement. Of note, upon further preexisting thrombocytosis.
investigation of the past medical history of those 4
patients, we found that two of them had splenectomy,
Authors contributions
which can account for their persistent thrombocytosis.
An unexpected finding of our study, which has a GT planned the methodology, performed the formal
practical implication in the routine management of analysis, and wrote the manuscript. GB prepared the
IDA patients, is that clinicians often underdose the original draft. OO, OP, and HT collected the data and
iron administration. Although the total iron deficit participated in conceptualization. MK and MGM per
can be estimated with the Ganzoni equation, many formed the project supervision. All authors made con
practitioners infuse IV iron at a fixed dose of tributions to writing the manuscript and approved its
1000 mg, without a formal calculation of the required final version.
iron repletion [14]. In fact, as reported in the results
section, clinicians in our institution treated many IDA
Disclosure statement
patients with a fixed dose of 1000 mg of iron dextran
IV. This approach is presumably suboptimal for achiev No potential conflict of interest was reported by the
ing full replacement of the iron stores, because we ret author(s).
rospectively calculated a median total iron deficit of
1006 mg, according to the Ganzoni equation. This Informed consent
suggests that about half of our patients would have
required a greater dose of IV iron. In terms of platelet As this is a retrospective study, patient informed
response, we do not know if an increased iron sup consent was not required.
plementation would have led to a deeper reduction
in the platelet counts. Data availability statement
The major limitations of our study are its retrospec
The dataset used during this study is available on request
tive nature, the relatively small sample size, the lack of from the corresponding author.
a dose-dependent analysis of the hematologic par
ameters, and the lack of serial measurements over an
extended period of time. Moreover, we did not ORCID
assess the effect of iron replacement therapy on plate Giampaolo Talamo http://orcid.org/0009-0000-1781-1633
let function, using adhesion and aggregation studies.
The strength of our study is the inclusion of patients
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