Evidence map›Paper›PMID 33469189›Full record

ArticlePediatric research2021

Evaluation of angiogenic signaling molecules associated with reactive thrombocytosis in an iron-deficient rat model.

Jessica Garcia, Peggy Mankin, Manu Gnanamony, Pedro A de Alarcon

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Article in Pediatric research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.7field-weighted citation impact, top 31% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 5 citations in OpenAlex.

  1. Mechanisms of Thrombocytosis in Iron-Deficiency Anemia.European journal of haematology · 2026
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

4 authors at 2 institutions in 1 country.

Jessica GarciaDepartment of Pediatrics, Division of Hematology/Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA. Jessica.garcia@utsouthwestern.edu.
Peggy MankinDepartment of Pediatrics, Division of Hematology/Oncology, University of Illinois College of Medicine Peoria, Peoria, IL, USA.
Manu GnanamonyDepartment of Pediatrics, Division of Hematology/Oncology, University of Illinois College of Medicine Peoria, Peoria, IL, USA.
Pedro A de AlarconDepartment of Pediatrics, Division of Hematology/Oncology, University of Illinois College of Medicine Peoria, Peoria, IL, USA.
Illinois College · USThe University of Texas Southwestern Medical Center · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundIron deficiency anemia (IDA)-induced reactive thrombocytosis can occur in children and adults. The underlying mechanism for this phenomenon is indeterminate. Traditional cytokines such as thrombopoietin (TPO), interleukin-6 (IL-6), and IL-11 involved in megakaryopoiesis have not been shown to be the cause. Recent studies suggest that growth factors and signaling molecules involved with angiogenesis influence the proliferation and differentiation of megakaryocytes.

methodsWe investigated the possible association between angiogenic cytokines with reactive thrombocytosis due to IDA in an iron-deficient (ID) rat model. Complete blood count, iron panels, and TPO levels were measured at baseline and 5 weeks later in both control (C) and ID rats. Angiogenic cytokines were evaluated in the bone marrow in all rats.

resultsWe successfully induced IDA in our rats by phlebotomy and reduced iron diet. We did not find an increase of TPO in ID rats. A review of the bone marrow showed an increase in the number of megakaryocytes, vascular structures, as well as increased intensity of stain for vascular endothelial growth factor (VEGF), and CXC chemokine receptor 4 (CXCR4) in rats with IDA compared to controls.

conclusionsOur results of histological bone marrow data suggest an important role for angiogenesis in the development of IDA-induced thrombocytosis. IMPACT: Thrombocytosis is common with IDA in both children and adults, but the mechanism is unclear. We confirmed that TPO is not the major driver of iron deficiency-associated thrombocytosis. We confirmed the increase in the number of megakaryocytes in the bone marrow despite stable TPO levels. We provided evidence supporting an important role of angiogenesis in megakaryocytopoiesis/thrombopoiesis with increased vascular structures and angiogenic cytokines in the bone marrow of iron-deficient rats. The demonstration that angiogenesis may play an important role in secondary thrombocytosis could lead to a new approach in treating symptomatic reactive thrombocytosis by targeting angiogenesis.

Indexed as

Neovascularization, PathologicThrombopoiesisAnemia, Iron-DeficiencyAnimalsBone MarrowDisease Models, AnimalMaleMegakaryocytesRatsRats, Sprague-DawleyReceptors, CXCR4Signal TransductionThrombocytosisThrombopoietinVascular Endothelial Growth Factor ACxcr4 protein, ratReceptors, CXCR4ThrombopoietinVascular Endothelial Growth Factor Avascular endothelial growth factor A, rat

Identifiers

PMID33469189
OpenAlexW3122451182

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.