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Iron-deficiency anemia as a rare cause of cerebral venous thrombosis and pulmonary embolism.
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PMID:  22701123     Owner:  NLM     Status:  PubMed-not-MEDLINE    
Abstract/OtherAbstract:
Cerebral venous thrombosis (CVT) is a relatively rare cause of stroke and has a wide spectrum of unspecific symptoms, which may delay diagnosis. There are many etiologies, including hematological disorders, trauma, infection, and dehydration. Iron-deficiency anemia (IDA) has been reported as an extremely rare cause of CVT, especially in adults.
Authors:
Nicolas Nicastro; Armin Schnider; Béatrice Leemann
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Publication Detail:
Type:  Journal Article     Date:  2012-05-31
Journal Detail:
Title:  Case reports in medicine     Volume:  2012     ISSN:  1687-9635     ISO Abbreviation:  Case Rep Med     Publication Date:  2012  
Date Detail:
Created Date:  2012-06-15     Completed Date:  2012-08-23     Revised Date:  2013-02-21    
Medline Journal Info:
Nlm Unique ID:  101512910     Medline TA:  Case Rep Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  497814     Citation Subset:  -    
Affiliation:
Division of Neurorehabilitation, Department of Clinical Neurosciences, Geneva University Hospital (HUG), 1206 Genève, Switzerland.
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Journal Information
Journal ID (nlm-ta): Case Report Med
Journal ID (iso-abbrev): Case Report Med
Journal ID (publisher-id): CRIM
ISSN: 1687-9627
ISSN: 1687-9635
Publisher: Hindawi Publishing Corporation
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Copyright © 2012 Nicolas Nicastro et al.
open-access:
Received Day: 22 Month: 1 Year: 2012
Revision Received Day: 5 Month: 4 Year: 2012
Accepted Day: 10 Month: 4 Year: 2012
Print publication date: Year: 2012
Electronic publication date: Day: 31 Month: 5 Year: 2012
Volume: 2012E-location ID: 497814
ID: 3369515
PubMed Id: 22701123
DOI: 10.1155/2012/497814

Iron-Deficiency Anemia as a Rare Cause of Cerebral Venous Thrombosis and Pulmonary Embolism
Nicolas NicastroI1*
Armin SchniderI1
Béatrice LeemannI1
Division of Neurorehabilitation, Department of Clinical Neurosciences, Geneva University Hospital (HUG), 1206 Genève, Switzerland
Correspondence: *Nicolas Nicastro: nicolasnicastro@gmail.com
[other] Academic Editor: Richard A. Wennberg

1. Introduction

Cerebral venous thrombosis (CVT) and pulmonary embolism (PE) share many risk factors such as hematological disorder, contraceptive use, tumor, dehydration, and trauma [1]. Iron-deficiency anemia (IDA) has been described as a cause of several adult cases of CVT the last few years [2, 3].


2. Case Report

A 63-year-old woman with no past history of coagulation abnormality, recent trauma, or hormonal substitution experienced sudden onset of headache followed by installation of right hemiplegia and global aphasia. Computed tomography and subsequent brain MRI revealed massive left frontotemporal hemorrhagic infarction and thrombosis of the superior sagittal sinus, left sigmoid/transverse sinus, and cortical vein (Figures 1, 2, and 3). Subsequently, chest tomography showed bilateral subsegmentary pulmonary embolism (Figure 4). Doppler did not reveal any deep venous thrombosis of the lower limbs.

The laboratory data showed severe hypochromic microcytic anemia with hemoglobin value of 3,4 g/L (normal range: 12–16). Serum iron concentration was 1 μmol/L (N = 5–30), and ferritin concentration was 2 mg/dL (N = 11–137). No B12 vitamin or folate deficiency was found. Screening for coagulopathy was normal, including factor II, factor V (Leyden), activated protein C resistance, and antiphospholipid antibodies. Protein C, protein S, and antithrombin III were not interpretable because of early vitamin K antagonists therapy. Protein immunofixation electrophoresis demonstrated no gammopathy. Upper gastrointestinal and lower digestive endoscopies, mammography, endovaginal echography, thoracoabdominal and pelvic computed tomography were performed and failed to detect any malignant disease, source of active bleeding, or pelvic vein thrombosis.

The patient was treated by blood transfusion and anticoagulation with intravenous heparin, followed by vitamin K antagonists (acenocoumarol) for a total duration of six months. The brain MRI performed one month after the onset showed an almost complete repermeabilisation of the cerebral venous sinuses.

The patient's right hemiparesis gradually improved, as well as her global aphasia. The patient was discharged three months after the onset. The anemia gradually improved with a hemoglobin value of 13,0 g/L. Our assumption regarding the origin of the anemia was a vegetarian diet without a proper iron substitution.


3. Discussion

This case shows simultaneous thrombosis of multiple cerebral venous sinuses and pulmonary embolism associated with iron-deficiency anemia. As stated by Diaz et al. [4], concomitant pulmonary embolism was found in 11% of 203 cases of intracranial venous thrombosis. Several mechanisms have been proposed to explain the association between IDA and thrombosis, as iron is an important regulator of thrombopoiesis [5]: low iron levels disinhibit megakaryocyte activity [6], which provokes secondary thrombocytosis, thus leading to a hypercoagulable state [7]. In addition, microcytosis alters red cells deformability, which increases viscosity and possibly the risk of venous thrombosis [8]. Finally, anemic hypoxia secondary to iron deficiency may occur as the oxygen-carrying capacity of erythrocytes decreases, especially in situations where the metabolic demands are increased. All these conditions lead to a turbulent blood flow, causing platelets to come more frequently in contact with the endothelial lining [9].

In their prospective study of 121 patients with iron-deficiency anemia and cerebral venous thrombosis [10], Stolz et al. suggest a significant association of severe anemia (Hb < 90 g/L) and CVT. Our paper seems to support the fact that anemia may play a consistent role in the development of CVT. Concomitant pulmonary embolism could be explained by a local arterial thrombus, possibly also induced by anemia. Another hypothesis would be the embolization of a cerebral vein clot to the pulmonary arteries, as mentioned by Diaz et al. [4].


Acknowledgments

The authors would like to thank Dr. D. Botsikas and Dr. S. Haller from the Department of Medical Imaging of the Geneva University Hospital, for their precious help in reviewing and selecting the diagnostic imaging.


References
1. Masuhr F,Mehraein S,Einhäupl K. Cerebral venous and sinus thrombosisJournal of NeurologyYear: 20042511112314999484
2. Balci K,Utku U,Asil T,Büyükkoyuncu N. Deep cerebral vein thrombosis associated with iron deficiency anaemia in adultsJournal of Clinical NeuroscienceYear: 200714218118417161294
3. Huang PH,Su JJ,Lin PH. Iron deficiency anemia—a rare etiology of sinus thrombosis in adultsActa Neurologica TaiwanicaYear: 201019212513020714964
4. Diaz JM,Schiffman JS,Urban ES,Maccario M. Superior sagittal sinus thrombosis and pulmonary embolism: a syndrome rediscoveredActa Neurologica ScandinavicaYear: 19928643903961455986
5. Franchini M,Targher G,Montagnana M,Lippi G. Iron and thrombosisAnnals of HematologyYear: 200887316717318066546
6. Habis A,Hobson WL,Greenberg R. Cerebral sinovenous thrombosis in a toddler with iron deficiency anemiaPediatric Emergency CareYear: 2010261184885121057282
7. Beguin Y. Erythropoietin and platelet productionHaematologicaYear: 199984654154710366799
8. Ogata T,Kamouchi M,Kitazono T,et al. Cerebral venous thrombosis associated with iron deficiency anemiaJournal of Stroke and Cerebrovascular DiseasesYear: 200817642642818984440
9. Hartfield DS,Lowry NJ,Keene DL,Yager JY. Iron deficiency: a cause of stroke in infants and childrenPediatric NeurologyYear: 199716150539044402
10. Stolz E,Valdueza JM,Grebe M,et al. Anemia as a risk factor for cerebral venous thrombosis? An old hypothesis revisited: results of a prospective studyJournal of NeurologyYear: 2007254672973417450317

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