Cargando…

Iron deficiency-induced thrombocytosis increases thrombotic tendency in rats

Iron deficiency (ID) is globally prevalent, and apart from anemia is associated with thrombocytosis. While considered benign, studies linking thrombotic events with prior ID anemia suggest otherwise. In this study we used animal models to assess the influence of ID on thrombotic tendency. Sprague-Da...

Descripción completa

Detalles Bibliográficos
Autores principales: Jimenez, Kristine, Leitner, Florentina, Leitner, Aran, Scharbert, Gisela, Schwabl, Philipp, Kramer, Anne-Margarethe, Krnjic, Anita, Friske, Joachim, Helbich, Thomas, Evstatiev, Rayko, Khare, Vineeta, Gasche, Christoph
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Fondazione Ferrata Storti 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7928018/
https://www.ncbi.nlm.nih.gov/pubmed/32079699
http://dx.doi.org/10.3324/haematol.2019.245092
_version_ 1783659777702756352
author Jimenez, Kristine
Leitner, Florentina
Leitner, Aran
Scharbert, Gisela
Schwabl, Philipp
Kramer, Anne-Margarethe
Krnjic, Anita
Friske, Joachim
Helbich, Thomas
Evstatiev, Rayko
Khare, Vineeta
Gasche, Christoph
author_facet Jimenez, Kristine
Leitner, Florentina
Leitner, Aran
Scharbert, Gisela
Schwabl, Philipp
Kramer, Anne-Margarethe
Krnjic, Anita
Friske, Joachim
Helbich, Thomas
Evstatiev, Rayko
Khare, Vineeta
Gasche, Christoph
author_sort Jimenez, Kristine
collection PubMed
description Iron deficiency (ID) is globally prevalent, and apart from anemia is associated with thrombocytosis. While considered benign, studies linking thrombotic events with prior ID anemia suggest otherwise. In this study we used animal models to assess the influence of ID on thrombotic tendency. Sprague-Dawley rats were fed control or iron-deficient diets and ferric carboxymaltose was used to reverse ID. Thrombosis was induced by stenosis of the inferior vena cava or damage to the right carotid artery using ferric chloride. Thrombi were evaluated histologically and by high frequency ultrasound in the venous model. ID consistently induced thrombocytosis alongside anemia. The growth of venous thrombi and the final dimensions of both arterial and venous thrombi were greater in animals with ID. In both models, platelet numbers correlated with the final thrombus size, with thrombi in iron-deficient animals having the largest platelet areas. Platelet function was also evaluated in surgically-naïve rats. Coagulability, determined by thromboelasto - graphy, and hemostasis, evaluated by tail transection, were enhanced in the animals with ID. Platelet P-selectin expression and plasma P-selectin levels were both higher in animals with ID. Platelet adhesion and aggregation in ID was impaired under shear flow but was intact in static assays. Iron replacement therapy reversed all ID-related changes in hematologic parameters, thrombus dimensions, and platelet assays. In summary, ID alone increases thrombotic tendency. Iron replacement therapy reverses these changes, making it a viable strategy for the prevention of ID-related thrombotic disease. This may be of importance in patients with chronic illnesses who may already be at increased risk of thrombosis, such as those with inflammatory bowel disease, chronic kidney disease, or cancer.
format Online
Article
Text
id pubmed-7928018
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Fondazione Ferrata Storti
record_format MEDLINE/PubMed
spelling pubmed-79280182021-03-05 Iron deficiency-induced thrombocytosis increases thrombotic tendency in rats Jimenez, Kristine Leitner, Florentina Leitner, Aran Scharbert, Gisela Schwabl, Philipp Kramer, Anne-Margarethe Krnjic, Anita Friske, Joachim Helbich, Thomas Evstatiev, Rayko Khare, Vineeta Gasche, Christoph Haematologica Article Iron deficiency (ID) is globally prevalent, and apart from anemia is associated with thrombocytosis. While considered benign, studies linking thrombotic events with prior ID anemia suggest otherwise. In this study we used animal models to assess the influence of ID on thrombotic tendency. Sprague-Dawley rats were fed control or iron-deficient diets and ferric carboxymaltose was used to reverse ID. Thrombosis was induced by stenosis of the inferior vena cava or damage to the right carotid artery using ferric chloride. Thrombi were evaluated histologically and by high frequency ultrasound in the venous model. ID consistently induced thrombocytosis alongside anemia. The growth of venous thrombi and the final dimensions of both arterial and venous thrombi were greater in animals with ID. In both models, platelet numbers correlated with the final thrombus size, with thrombi in iron-deficient animals having the largest platelet areas. Platelet function was also evaluated in surgically-naïve rats. Coagulability, determined by thromboelasto - graphy, and hemostasis, evaluated by tail transection, were enhanced in the animals with ID. Platelet P-selectin expression and plasma P-selectin levels were both higher in animals with ID. Platelet adhesion and aggregation in ID was impaired under shear flow but was intact in static assays. Iron replacement therapy reversed all ID-related changes in hematologic parameters, thrombus dimensions, and platelet assays. In summary, ID alone increases thrombotic tendency. Iron replacement therapy reverses these changes, making it a viable strategy for the prevention of ID-related thrombotic disease. This may be of importance in patients with chronic illnesses who may already be at increased risk of thrombosis, such as those with inflammatory bowel disease, chronic kidney disease, or cancer. Fondazione Ferrata Storti 2020-02-20 /pmc/articles/PMC7928018/ /pubmed/32079699 http://dx.doi.org/10.3324/haematol.2019.245092 Text en Copyright© 2021 Ferrata Storti Foundation http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution Noncommercial License (by-nc 4.0) which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.
spellingShingle Article
Jimenez, Kristine
Leitner, Florentina
Leitner, Aran
Scharbert, Gisela
Schwabl, Philipp
Kramer, Anne-Margarethe
Krnjic, Anita
Friske, Joachim
Helbich, Thomas
Evstatiev, Rayko
Khare, Vineeta
Gasche, Christoph
Iron deficiency-induced thrombocytosis increases thrombotic tendency in rats
title Iron deficiency-induced thrombocytosis increases thrombotic tendency in rats
title_full Iron deficiency-induced thrombocytosis increases thrombotic tendency in rats
title_fullStr Iron deficiency-induced thrombocytosis increases thrombotic tendency in rats
title_full_unstemmed Iron deficiency-induced thrombocytosis increases thrombotic tendency in rats
title_short Iron deficiency-induced thrombocytosis increases thrombotic tendency in rats
title_sort iron deficiency-induced thrombocytosis increases thrombotic tendency in rats
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7928018/
https://www.ncbi.nlm.nih.gov/pubmed/32079699
http://dx.doi.org/10.3324/haematol.2019.245092
work_keys_str_mv AT jimenezkristine irondeficiencyinducedthrombocytosisincreasesthrombotictendencyinrats
AT leitnerflorentina irondeficiencyinducedthrombocytosisincreasesthrombotictendencyinrats
AT leitneraran irondeficiencyinducedthrombocytosisincreasesthrombotictendencyinrats
AT scharbertgisela irondeficiencyinducedthrombocytosisincreasesthrombotictendencyinrats
AT schwablphilipp irondeficiencyinducedthrombocytosisincreasesthrombotictendencyinrats
AT kramerannemargarethe irondeficiencyinducedthrombocytosisincreasesthrombotictendencyinrats
AT krnjicanita irondeficiencyinducedthrombocytosisincreasesthrombotictendencyinrats
AT friskejoachim irondeficiencyinducedthrombocytosisincreasesthrombotictendencyinrats
AT helbichthomas irondeficiencyinducedthrombocytosisincreasesthrombotictendencyinrats
AT evstatievrayko irondeficiencyinducedthrombocytosisincreasesthrombotictendencyinrats
AT kharevineeta irondeficiencyinducedthrombocytosisincreasesthrombotictendencyinrats
AT gaschechristoph irondeficiencyinducedthrombocytosisincreasesthrombotictendencyinrats