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PLoS One. 2014 Feb 19;9(2):e88812. doi: 10.1371/journal.pone.0088812. eCollection 2014.

Ischaemic strokes in patients with pulmonary arteriovenous malformations and hereditary hemorrhagic telangiectasia: associations with iron deficiency and platelets.

Author information

1
National Heart & Lung Institute (NHLI) Cardiovascular Sciences, Imperial College London, United Kingdom.
2
National Heart & Lung Institute (NHLI) Cardiovascular Sciences, Imperial College London, United Kingdom ; Imperial College School of Medicine, Imperial College London, United Kingdom.
3
National Heart & Lung Institute (NHLI) Cardiovascular Sciences, Imperial College London, United Kingdom ; Respiratory Medicine, Imperial College Healthcare NHS Trust, London, United Kingdom ; Imperial College School of Medicine, Imperial College London, United Kingdom.
4
Respiratory Medicine, Imperial College Healthcare NHS Trust, London, United Kingdom ; Imperial College School of Medicine, Imperial College London, United Kingdom.
5
Haematology, Imperial College Healthcare NHS Trust, London, United Kingdom.
6
Haematology, Imperial College Healthcare NHS Trust, London, United Kingdom ; Centre for Haematology, Investigative Sciences, Imperial College London, United Kingdom.
7
Clinical Chemistry, Imperial College Healthcare NHS Trust, London, United Kingdom.
8
Respiratory Medicine, Imperial College Healthcare NHS Trust, London, United Kingdom.
9
Department of Imaging, Imperial College Healthcare NHS Trust, London, United Kingdom.

Abstract

BACKGROUND:

Pulmonary first pass filtration of particles marginally exceeding ∼7 µm (the size of a red blood cell) is used routinely in diagnostics, and allows cellular aggregates forming or entering the circulation in the preceding cardiac cycle to lodge safely in pulmonary capillaries/arterioles. Pulmonary arteriovenous malformations compromise capillary bed filtration, and are commonly associated with ischaemic stroke. Cohorts with CT-scan evident malformations associated with the highest contrast echocardiographic shunt grades are known to be at higher stroke risk. Our goal was to identify within this broad grouping, which patients were at higher risk of stroke.

METHODOLOGY:

497 consecutive patients with CT-proven pulmonary arteriovenous malformations due to hereditary haemorrhagic telangiectasia were studied. Relationships with radiologically-confirmed clinical ischaemic stroke were examined using logistic regression, receiver operating characteristic analyses, and platelet studies.

PRINCIPAL FINDINGS:

Sixty-one individuals (12.3%) had acute, non-iatrogenic ischaemic clinical strokes at a median age of 52 (IQR 41-63) years. In crude and age-adjusted logistic regression, stroke risk was associated not with venous thromboemboli or conventional neurovascular risk factors, but with low serum iron (adjusted odds ratio 0.96 [95% confidence intervals 0.92, 1.00]), and more weakly with low oxygen saturations reflecting a larger right-to-left shunt (adjusted OR 0.96 [0.92, 1.01]). For the same pulmonary arteriovenous malformations, the stroke risk would approximately double with serum iron 6 µmol/L compared to mid-normal range (7-27 µmol/L). Platelet studies confirmed overlooked data that iron deficiency is associated with exuberant platelet aggregation to serotonin (5HT), correcting following iron treatment. By MANOVA, adjusting for participant and 5HT, iron or ferritin explained 14% of the variance in log-transformed aggregation-rate (p = 0.039/p = 0.021).

SIGNIFICANCE:

These data suggest that patients with compromised pulmonary capillary filtration due to pulmonary arteriovenous malformations are at increased risk of ischaemic stroke if they are iron deficient, and that mechanisms are likely to include enhanced aggregation of circulating platelets.

PMID:
24586400
PMCID:
PMC3929507
DOI:
10.1371/journal.pone.0088812
[Indexed for MEDLINE]
Free PMC Article

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