Ischaemic Strokes in Patients with Pulmonary Arteriovenous Malformations and Hereditary Hemorrhagic Telangiectasia: Associations with Iron Deficiency and Platelets
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{"title"=>"Ischaemic strokes in patients with pulmonary arteriovenous malformations and hereditary hemorrhagic telangiectasia: Associations with iron deficiency and platelets", "type"=>"journal", "authors"=>[{"first_name"=>"Claire L.", "last_name"=>"Shovlin", "scopus_author_id"=>"7003333972"}, {"first_name"=>"Basel", "last_name"=>"Chamali", "scopus_author_id"=>"56080936800"}, {"first_name"=>"Vatshalan", "last_name"=>"Santhirapala", "scopus_author_id"=>"56081109900"}, {"first_name"=>"John A.", "last_name"=>"Livesey", "scopus_author_id"=>"54890607100"}, {"first_name"=>"Gillian", "last_name"=>"Angus", "scopus_author_id"=>"36054483600"}, {"first_name"=>"Richard", "last_name"=>"Manning", "scopus_author_id"=>"57195375316"}, {"first_name"=>"Michael A.", "last_name"=>"Laffan", "scopus_author_id"=>"57194518699"}, {"first_name"=>"John", "last_name"=>"Meek", "scopus_author_id"=>"56348641400"}, {"first_name"=>"Hannah C.", "last_name"=>"Tighe", "scopus_author_id"=>"25029578100"}, {"first_name"=>"James E.", "last_name"=>"Jackson", "scopus_author_id"=>"7404117325"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"372580071", "sgr"=>"84896761161", "pmid"=>"24586400", "scopus"=>"2-s2.0-84896761161", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "doi"=>"10.1371/journal.pone.0088812", "issn"=>"19326203"}, "id"=>"b46c3520-93d6-3be5-a56b-552d351a32eb", "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.\\n\\nMETHODOLOGY: 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.\\n\\nPRINCIPAL 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).\\n\\nSIGNIFICANCE: 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.", "link"=>"http://www.mendeley.com/research/ischaemic-strokes-patients-pulmonary-arteriovenous-malformations-hereditary-hemorrhagic-telangiectas", "reader_count"=>30, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Professor > Associate Professor"=>2, "Librarian"=>1, "Researcher"=>3, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>5, "Student > Postgraduate"=>1, "Student > Master"=>6, "Other"=>4, "Student > Bachelor"=>3, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Professor > Associate Professor"=>2, "Librarian"=>1, "Researcher"=>3, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>5, "Student > Postgraduate"=>1, "Student > Master"=>6, "Other"=>4, "Student > Bachelor"=>3, "Professor"=>1}, "reader_count_by_subject_area"=>{"Engineering"=>1, "Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>1, "Nursing and Health Professions"=>1, "Medicine and Dentistry"=>20, "Agricultural and Biological Sciences"=>4, "Computer Science"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>20}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>4}, "Computer Science"=>{"Computer Science"=>1}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Unspecified"=>{"Unspecified"=>2}}, "reader_count_by_country"=>{"Greece"=>1, "United States"=>1}, "group_count"=>5}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1391969", "https://ndownloader.figshare.com/files/1391970"], "description"=>"<div><p>Background</p><p>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.</p><p>Methodology</p><p>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.</p><p>Principal Findings</p><p>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).</p><p>Significance</p><p>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.</p></div>", "links"=>[], "tags"=>["cardiovascular", "Pulmonary vascular diseases", "stroke", "Venous thromboembolism", "Clinical genetics", "Autosomal dominant", "Diagnostic medicine", "pathology", "General pathology", "biomarkers", "hematology", "anemia", "Iron deficiency anemia", "platelets", "neurology", "Cerebrovascular diseases", "nutrition", "Micronutrient deficiencies", "strokes", "patients", "pulmonary", "arteriovenous", "malformations", "hereditary", "hemorrhagic", "associations", "deficiency"], "article_id"=>939328, "categories"=>["Medicine"], "users"=>["Claire L. Shovlin", "Basel Chamali", "Vatshalan Santhirapala", "John A. Livesey", "Gillian Angus", "Richard Manning", "Michael A. Laffan", "John Meek", "Hannah C. Tighe", "James E. Jackson"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0088812.s001", "https://dx.doi.org/10.1371/journal.pone.0088812.s002"], "stats"=>{"downloads"=>3, "page_views"=>20, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Ischaemic_Strokes_in_Patients_with_Pulmonary_Arteriovenous_Malformations_and_Hereditary_Hemorrhagic_Telangiectasia_Associations_with_Iron_Deficiency_and_Platelets_/939328", "title"=>"Ischaemic Strokes in Patients with Pulmonary Arteriovenous Malformations and Hereditary Hemorrhagic Telangiectasia: Associations with Iron Deficiency and Platelets", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2014-02-19 03:40:06"}
  • {"files"=>["https://ndownloader.figshare.com/files/1391964"], "description"=>"<p>For patients presenting between 2006 and 2010, iron deficiency was assigned as absent (No ID) if ferritin, iron and T<i>f</i>SI were all clearly in the normal range (ferritin>20 µg/L, serum iron>11 µmol/L and T<i>f</i>SI>20%, N = 93). The groupings to examine iron deficiency were ferritin <15 µg/L (ferr<15, N = 20); ferritin <20 µg/L (ferr<20, N = 26); and serum iron <11 µmol/L (iron <11, N = 50). BMI, body mass index. MCV, mean corpuscular volume. MCH, mean corpuscular haemoglobin. MCHC, mean corpuscular haemoglobin concentration. T<i>f</i>SI, transferrin saturation index.</p>", "links"=>[], "tags"=>["cardiovascular", "Pulmonary vascular diseases", "stroke", "Venous thromboembolism", "Clinical genetics", "Autosomal dominant", "Diagnostic medicine", "pathology", "General pathology", "biomarkers", "hematology", "anemia", "Iron deficiency anemia", "platelets", "neurology", "Cerebrovascular diseases", "nutrition", "Micronutrient deficiencies", "deficiency"], "article_id"=>939323, "categories"=>["Medicine"], "users"=>["Claire L. Shovlin", "Basel Chamali", "Vatshalan Santhirapala", "John A. Livesey", "Gillian Angus", "Richard Manning", "Michael A. Laffan", "John Meek", "Hannah C. Tighe", "James E. Jackson"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0088812.t002", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Comparison_of_iron_deficiency_classifications_/939323", "title"=>"Comparison of iron deficiency classifications.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-02-19 03:40:06"}
  • {"files"=>["https://ndownloader.figshare.com/files/1391947"], "description"=>"<p><b>A</b>: Cartoon of the circulations indicating site of the pulmonary capillary filter, the dual pulmonary and bronchial/systemic arterial supply to lung tissue, and a pulmonary arteriovenous malformations (PAVM, red arrow). <b>B</b>: Relationship between quantified right-to-left shunt (measured using with <sup>99m</sup>Tc-labelled albumin macroaggregates (10–80 µm) or microspheres (7–25 µm)), with same-day oxygen saturation (SaO<sub>2</sub>), representing 309 paired values in 198 individuals since 1999. The linear regression coefficient of −1.22 (95% CI −1.31, −1.14; p<0.0001) indicates a strong relationship that explains 73% of the total variance in erect SaO<sub>2</sub> (adjusted r<sup>2</sup> 0.73). The shunt explained a smaller proportion of the total variance in supine SaO<sub>2</sub> (adjusted r<sup>2</sup> 0.54, data not shown). <b>C–F</b>: Representative right lateral brain images following injection of <sup>99m</sup>Tc-labelled albumin macroaggregates for shunt diagnosis and quantification: <b>C</b>) R-L shunt 48.8% of the cardiac output, associated with a resting SaO<sub>2</sub> of 59%. <b>D</b>) R-L shunt 25%; SaO<sub>2</sub> 83%. <b>E</b>) R-L shunt 7.7%; SaO<sub>2</sub> 93.7%. Note the intense activity in the lung apices as expected. <b>F</b>) R-L shunt 3.3%; SaO<sub>2</sub> 96%. Note that the gain has been turned up but no cerebral activity is visible. This is the same individual as in <b>D</b>), with the images taken 6 months before (<b>D</b>) and 3 months after (<b>F</b>) embolisation which obliterated the causative PAVMs.</p>", "links"=>[], "tags"=>["cardiovascular", "Pulmonary vascular diseases", "stroke", "Venous thromboembolism", "Clinical genetics", "Autosomal dominant", "Diagnostic medicine", "pathology", "General pathology", "biomarkers", "hematology", "anemia", "Iron deficiency anemia", "platelets", "neurology", "Cerebrovascular diseases", "nutrition", "Micronutrient deficiencies", "shunt", "hypoxaemia"], "article_id"=>939308, "categories"=>["Medicine"], "users"=>["Claire L. Shovlin", "Basel Chamali", "Vatshalan Santhirapala", "John A. Livesey", "Gillian Angus", "Richard Manning", "Michael A. Laffan", "John Meek", "Hannah C. Tighe", "James E. Jackson"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0088812.g001", "stats"=>{"downloads"=>3, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Right_to_left_shunt_and_hypoxaemia_evaluations_/939308", "title"=>"Right-to-left shunt and hypoxaemia evaluations.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-02-19 03:40:06"}
  • {"files"=>["https://ndownloader.figshare.com/files/1391957"], "description"=>"<p>Solid lines indicate controls; dotted lines represent the iron deficient group. Error bars represent standard error of the mean. <b>A</b>) Total aggregation in response to ADP at 5–50 µmol/L. <b>B</b>) Rate of aggregation in response to ADP. Since circulating blood should spend less than two seconds between pulmonary transits, the rate of aggregation may be particularly relevant. <b>C</b>) Total aggregation in response to 5HT. <b>D</b>) Rate of aggregation in response to 5HT.</p>", "links"=>[], "tags"=>["cardiovascular", "Pulmonary vascular diseases", "stroke", "Venous thromboembolism", "Clinical genetics", "Autosomal dominant", "Diagnostic medicine", "pathology", "General pathology", "biomarkers", "hematology", "anemia", "Iron deficiency anemia", "platelets", "neurology", "Cerebrovascular diseases", "nutrition", "Micronutrient deficiencies", "platelet", "curves", "agonists", "deficient", "patients"], "article_id"=>939317, "categories"=>["Medicine"], "users"=>["Claire L. Shovlin", "Basel Chamali", "Vatshalan Santhirapala", "John A. Livesey", "Gillian Angus", "Richard Manning", "Michael A. Laffan", "John Meek", "Hannah C. Tighe", "James E. Jackson"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0088812.g004", "stats"=>{"downloads"=>2, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Comparison_of_platelet_dose_response_curves_in_response_to_agonists_in_iron_deficient_patients_and_controls_/939317", "title"=>"Comparison of platelet dose response curves in response to agonists in iron deficient patients and controls.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-02-19 03:40:06"}
  • {"files"=>["https://ndownloader.figshare.com/files/1391949"], "description"=>"<p><b>A</b>) Cumulative survival until first stroke: The solid line is modelled from the 129 patients with serum iron <8 µmol/L; dotted line from the 161 patients with serum iron >19 µmol/L. Shaded areas indicate 95% confidence intervals. <b>B</b>) Comparison of the stroke risk ROC models from myocardial infarction and serum iron (base model, black line/symbols), and strongest model generated from captured physiological variables, excluding the outcome measure of myocardial infarction (red line/symbols). The two models provide equivalent areas under the curve of 0.65 and 0·66 (p = 0.88). In the physiological ROC model, stroke risk was higher not only with lower serum iron (OR 0.95 [95% CI 0.90, 1.01]), but also with lower PAP(mean) (OR 0.94 [0.86, 1.03]); higher fibrinogen (OR 1.50 [0.95, 2.33]), lower SaO<sub>2</sub> (OR 0.98 [95% CI 0.93, 1·03]), and in women (OR 1.57 [0.71, 3.47]).</p>", "links"=>[], "tags"=>["cardiovascular", "Pulmonary vascular diseases", "stroke", "Venous thromboembolism", "Clinical genetics", "Autosomal dominant", "Diagnostic medicine", "pathology", "General pathology", "biomarkers", "hematology", "anemia", "Iron deficiency anemia", "platelets", "neurology", "Cerebrovascular diseases", "nutrition", "Micronutrient deficiencies"], "article_id"=>939310, "categories"=>["Medicine"], "users"=>["Claire L. Shovlin", "Basel Chamali", "Vatshalan Santhirapala", "John A. Livesey", "Gillian Angus", "Richard Manning", "Michael A. Laffan", "John Meek", "Hannah C. Tighe", "James E. Jackson"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0088812.g002", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Stroke_incidence_/939310", "title"=>"Stroke incidence.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-02-19 03:40:06"}
  • {"files"=>["https://ndownloader.figshare.com/files/1391965"], "description"=>"<p>SaO<sub>2</sub> values measured by pulse oximetry following 7, 8, 9 and10 minutes standing. The variability within these measurements has not been presented previously. 522 consecutive datasets for the 165 PAVM patients first presenting between 2006 and 2010 were analysed and represent their datasets at presentation and in follow up. To illustrate reproducibility across all severities of hypoxaemia, datasets were divided into quintiles based on SaO<sub>2</sub>, each with over 100 datasets. SD, standard deviation.</p>", "links"=>[], "tags"=>["cardiovascular", "Pulmonary vascular diseases", "stroke", "Venous thromboembolism", "Clinical genetics", "Autosomal dominant", "Diagnostic medicine", "pathology", "General pathology", "biomarkers", "hematology", "anemia", "Iron deficiency anemia", "platelets", "neurology", "Cerebrovascular diseases", "nutrition", "Micronutrient deficiencies"], "article_id"=>939324, "categories"=>["Medicine"], "users"=>["Claire L. Shovlin", "Basel Chamali", "Vatshalan Santhirapala", "John A. Livesey", "Gillian Angus", "Richard Manning", "Michael A. Laffan", "John Meek", "Hannah C. Tighe", "James E. Jackson"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0088812.t001", "stats"=>{"downloads"=>1, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_SaO_2_measurement_reproducibility_/939324", "title"=>"SaO<sub>2</sub> measurement reproducibility.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-02-19 03:40:06"}
  • {"files"=>["https://ndownloader.figshare.com/files/1391962"], "description"=>"<p>Demographics of individual and combined series, with p values calculated by Mann Whitney. N, number of recordings of variable in series.</p>", "links"=>[], "tags"=>["cardiovascular", "Pulmonary vascular diseases", "stroke", "Venous thromboembolism", "Clinical genetics", "Autosomal dominant", "Diagnostic medicine", "pathology", "General pathology", "biomarkers", "hematology", "anemia", "Iron deficiency anemia", "platelets", "neurology", "Cerebrovascular diseases", "nutrition", "Micronutrient deficiencies"], "article_id"=>939321, "categories"=>["Medicine"], "users"=>["Claire L. Shovlin", "Basel Chamali", "Vatshalan Santhirapala", "John A. Livesey", "Gillian Angus", "Richard Manning", "Michael A. Laffan", "John Meek", "Hannah C. Tighe", "James E. Jackson"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0088812.t003", "stats"=>{"downloads"=>1, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Population_Demographics_/939321", "title"=>"Population Demographics.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-02-19 03:40:06"}
  • {"files"=>["https://ndownloader.figshare.com/files/1391960"], "description"=>"<p>Full list of age/gender, and serum iron-adjusted odds ratios for ischaemic stroke risk for the specified variable, where an inverse association with stroke risk is indicated by an odds ratio <1. N: number of datasets available. CI, confidence intervals, AF, atrial fibrillation. Pseudo r<sup>2</sup> indicates the proportion of stroke variance explained by age, gender, and the specified variable. P values were calculated by the non parametric Wald test which does not assume independence of variables. † Quadratic regression plots for stroke risk versus serum iron or SaO<sub>2</sub> presented in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0088812#pone.0088812.s001\" target=\"_blank\">Figure S1</a>. Note <i>p</i> = 0.047 significant at FDR = 0.05 level.</p>", "links"=>[], "tags"=>["cardiovascular", "Pulmonary vascular diseases", "stroke", "Venous thromboembolism", "Clinical genetics", "Autosomal dominant", "Diagnostic medicine", "pathology", "General pathology", "biomarkers", "hematology", "anemia", "Iron deficiency anemia", "platelets", "neurology", "Cerebrovascular diseases", "nutrition", "Micronutrient deficiencies", "ratios", "ischaemic"], "article_id"=>939319, "categories"=>["Medicine"], "users"=>["Claire L. Shovlin", "Basel Chamali", "Vatshalan Santhirapala", "John A. Livesey", "Gillian Angus", "Richard Manning", "Michael A. Laffan", "John Meek", "Hannah C. Tighe", "James E. Jackson"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0088812.t005", "stats"=>{"downloads"=>2, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Adjusted_odds_ratios_for_ischaemic_stroke_risk_/939319", "title"=>"Adjusted odds ratios for ischaemic stroke risk.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-02-19 03:40:06"}
  • {"files"=>["https://ndownloader.figshare.com/files/1391961"], "description"=>"<p>*Note that silent lacunar infarcts, or silent infarcts at other sites, were excluded by the study methodology. Data exclude four iatrogenic strokes of known aetiology (one following thrombus injection through giving set; one at time of cerebral angiography; one at time of pulmonary angiography; and one progressive following stereotactic radiotherapy), but otherwise include all first clinical strokes of ischaemic aetiology.</p>", "links"=>[], "tags"=>["cardiovascular", "Pulmonary vascular diseases", "stroke", "Venous thromboembolism", "Clinical genetics", "Autosomal dominant", "Diagnostic medicine", "pathology", "General pathology", "biomarkers", "hematology", "anemia", "Iron deficiency anemia", "platelets", "neurology", "Cerebrovascular diseases", "nutrition", "Micronutrient deficiencies", "ischaemic"], "article_id"=>939320, "categories"=>["Medicine"], "users"=>["Claire L. Shovlin", "Basel Chamali", "Vatshalan Santhirapala", "John A. Livesey", "Gillian Angus", "Richard Manning", "Michael A. Laffan", "John Meek", "Hannah C. Tighe", "James E. Jackson"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0088812.t004", "stats"=>{"downloads"=>1, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Details_of_clinical_ischaemic_strokes_/939320", "title"=>"Details of clinical ischaemic strokes.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-02-19 03:40:06"}
  • {"files"=>["https://ndownloader.figshare.com/files/1391959"], "description"=>"<p><b>A</b>) The distribution for aggregation achieved was skewed and normalised by log transformation (<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0088812#pone.0088812.s002\" target=\"_blank\">Figure S2A</a>). (Ln)aggregation was therefore used as the dependent variable for regression. A model restricted to first order variables was not as strong as the final model including the iron-ferritin interaction term (iron*ferritin (µg*µmol/L<sup>2</sup>)). This model of 24 assays explained 72% of the variance of (ln)aggregation (p = 0.0001). <b>B</b>) The distribution for rate of aggregation was skewed and normalised by log transformation (<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0088812#pone.0088812.s002\" target=\"_blank\">Figure S2B</a>). (Ln)rate of aggregation was therefore used as the dependent variable for regression. Final model for (ln)rate of aggregation in all 22 available assays, in a model that explained 77.4% of the variance (p<0.0001).The crude coefficient with iron was similar at −0.036 [95% CI −0.053, −0.0187], p<0.0001. There was no relationship with 5HT concentration in univariate or iron/ferritin- adjusted regression (data not shown).</p>", "links"=>[], "tags"=>["cardiovascular", "Pulmonary vascular diseases", "stroke", "Venous thromboembolism", "Clinical genetics", "Autosomal dominant", "Diagnostic medicine", "pathology", "General pathology", "biomarkers", "hematology", "anemia", "Iron deficiency anemia", "platelets", "neurology", "Cerebrovascular diseases", "nutrition", "Micronutrient deficiencies", "regression", "5ht-induced", "aggregation"], "article_id"=>939318, "categories"=>["Medicine"], "users"=>["Claire L. Shovlin", "Basel Chamali", "Vatshalan Santhirapala", "John A. Livesey", "Gillian Angus", "Richard Manning", "Michael A. Laffan", "John Meek", "Hannah C. Tighe", "James E. Jackson"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0088812.t006", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Multiple_regression_analyses_of_5HT_induced_aggregation_parameters_/939318", "title"=>"Multiple regression analyses of 5HT-induced aggregation parameters.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-02-19 03:40:06"}
  • {"files"=>["https://ndownloader.figshare.com/files/1391954"], "description"=>"<p><b>A</b>) Typical control and iron deficient responses to ADP at 5 (blue), 10 (green), 20 (red) and 50 (black)µM. <b>B</b>) Typical control dose response curves to 5HT at 20 (blue), 200 (green), 2,000 (red) and 20,000 (black) µM–note the absence of the secondary wave of aggregation. <b>C</b>) Representative 5HT dose response curves displaying delayed secondary wave of aggregation observed in all severely iron deficient patients (hemoglobins 5.0–7.5 g/dl). The traces illustrated (5HT at 20 (blue), 200 (green), 2,000 (red) and 20,000 (black)) µM were from an individual with ferritin 4 µg/L, iron 3 µmol/l, hemoglobin 7.5 g/dl. <b>D</b>) Traces from the same individual as in (<b>C</b>), following a 6 month course of iron that resulted in improved iron indices (ferritin 31 µg/L, iron 7 µmol/l, hemoglobin 10.5 g/dl). Note that despite further treatments, iron deficiency persisted due to ongoing hemorrhagic losses. Aggregation curves are displayed for 5HT at 20 (black), 200 (green), 2,000 (red) and 20,000 (blue)µM.</p>", "links"=>[], "tags"=>["cardiovascular", "Pulmonary vascular diseases", "stroke", "Venous thromboembolism", "Clinical genetics", "Autosomal dominant", "Diagnostic medicine", "pathology", "General pathology", "biomarkers", "hematology", "anemia", "Iron deficiency anemia", "platelets", "neurology", "Cerebrovascular diseases", "nutrition", "Micronutrient deficiencies", "platelet"], "article_id"=>939315, "categories"=>["Medicine"], "users"=>["Claire L. Shovlin", "Basel Chamali", "Vatshalan Santhirapala", "John A. Livesey", "Gillian Angus", "Richard Manning", "Michael A. Laffan", "John Meek", "Hannah C. Tighe", "James E. Jackson"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0088812.g003", "stats"=>{"downloads"=>1, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Representative_platelet_dose_response_curves_/939315", "title"=>"Representative platelet dose response curves.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-02-19 03:40:06"}

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