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

PLoS ONE

Volumn 9, Issue 2, 2014, Pages

  Shovlin, Claire L ^a   Chamali, Basel ^a,c   Santhirapala, Vatshalan ^a,b,c   Livesey, John A ^b,c   Angus, Gillian ^b   Manning, Richard ^b   Laffan, Michael A ^b,d   Meek, John ^b   Tighe, Hannah C ^b   Jackson, James E ^b  

^a NATIONAL HEART AND LUNG INSTITUTE   (United Kingdom)

^b IMPERIAL COLLEGE HEALTHCARE NHS TRUST   (United Kingdom)

^c IMPERIAL COLLEGE SCHOOL OF MEDICINE   (United Kingdom)

^d IMPERIAL COLLEGE LONDON   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

FERRITIN; IRON; SEROTONIN;

ADULT; ARTICLE; BLOOD FILTRATION; BRAIN ISCHEMIA; CARDIOVASCULAR RISK; COMPUTER ASSISTED TOMOGRAPHY; CONTRAST ENHANCEMENT; CONTROLLED STUDY; DISEASE ASSOCIATION; FEMALE; HEART RIGHT LEFT SHUNT; HIGH RISK POPULATION; HUMAN; IRON BLOOD LEVEL; IRON DEFICIENCY; IRON THERAPY; MAJOR CLINICAL STUDY; MALE; NEUROLOGIC DISEASE; OXYGEN SATURATION; PULMONARY ARTERIOVENOUS FISTULA; RENDU OSLER WEBER DISEASE; RISK FACTOR; THROMBOCYTE AGGREGATION; THROMBOCYTOPENIA; VASCULAR DISEASE; VENOUS THROMBOEMBOLISM; CEREBROVASCULAR ACCIDENT; COMPLICATION; DEFICIENCY; METABOLISM; MIDDLE AGED; PATHOPHYSIOLOGY; PHYSIOLOGY; PULMONARY ARTERY; PULMONARY VEIN; THROMBOCYTE;

ADULT; BLOOD PLATELETS; BRAIN ISCHEMIA; FEMALE; HUMANS; IRON; MALE; MIDDLE AGED; PLATELET AGGREGATION; PULMONARY ARTERY; PULMONARY VEINS; RISK FACTORS; STROKE; TELANGIECTASIA, HEREDITARY HEMORRHAGIC;

EID: 84896761161     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0088812     Document Type: Article

References (84)

1. Shovlin CL, Jackson JE (2010) Pulmonary arteriovenous malformations and other vascular abnormalities. In: Mason RJ, Broaddus VC, Martin T, et al. editors. Murray and Nadel's Textbook of Respiratory Medicine.5th Edn. Philadelphia, Elsevier-Saunders. pp. 1261-1282.
2. Butler BD, Hills BA (1979) The lung as a filter for microbubbles. J Appl Physiol. 1979 47: 537-43. (Pubitemid 10206557)
3. Weibel ER (2009) What makes a good lung? The morphometric basis of lung function. Swiss Med Wkly 139 (27-28): 375-386.
4. Chilvers ER, Peters AM, George P, Hughes JMB, Allison DJ (1989) Quantification of right to left shunt through pulmonary arteriovenous malformations using 99Tcm albumin microspheres. Clin Radiol 39: 611-614. (Pubitemid 19019190)
5. Bajc M, Neilly JB, Miniati M, Schuemichen C, Meignan M, et al. (2009) EANM guidelines for ventilation/perfusion scintigraphy: Part 1. Pulmonary imaging with ventilation/perfusion single photon emission tomography. Eur J Nucl Med Mol Imaging 36: 1356-70.
6. Billinger M, Schwerzmann M, Rutishauser W, Wahl A, Windecker S, et al. (2013) Patent foramen ovale screening by ear oximetry in divers. Am J Cardiol. 111: 286-90.
7. Nakayama M, Nawa T, Chonan T, Endo K, Morikawa S, et al. (2012) Prevalence of pulmonary arteriovenous malformations as estimated by low-dose thoracic CT screening. Intern Med 51:1677-81
8. Whyte MK, Peters AM, Hughes JM, Henderson BL, Bellingan GJ, et al. (1992). Quantification of right to left shunt at rest and during exercise in patients with pulmonary arteriovenous malformations. Thorax 47: 790-796
9. Ueki T, Hughes JMB, Peters AM, Bellingan GJ, Mohammed MAM, et al. (1994) Oxygen and 99mTc-MAA shunt estimations in patients with pulmonary arteriovenous malformations: effects of changes in posture and lung volume. Thorax 49: 327-331. (Pubitemid 24149194)
10. Thompson RD, Jackson J, Peters AM, Doré CJ, Hughes JM (1999) Sensitivity and specificity of radioisotope right-left shunt measurements and pulse oximetry for the early detection of pulmonary arteriovenous malformations. Chest 115: 109-13. (Pubitemid 29047061)
11. Mager JJ, Zanen P, Verzijlbergen F, Westermann CJ, Haitjema T, et al. (2002) Quantification of right-to-left shunt with (99 m) Tc-labelled albumin macroaggregates and 100% oxygen in patients with hereditary haemorrhagic telangiectasia. Clin Sci (Lond) 102: 127-34. (Pubitemid 34185040)
12. Feinstein J, Moore P, Rosenthal D, Puchalski M, Brook M (2002) Comparison of contrast echocardiography versus cardiac catheterisation for detection of pulmonary arteriovenous malformations. Am J Cardiol 89: 281-5. (Pubitemid 34113789)
13. Gazzaniga P, Buscarini E, Leandro G, Reduzzi L, Grosso M, et al. (2008) Contrast echocardiography for pulmonary arteriovenous malformations (PAVMs) screening: Does any bubble matter? Eur J Echocardiogr 10: 513-8.
14. Barzilai B, Waggoner A, Spessert C, Picus D, Goodenberger D (1991) Two-dimensional contrast echocardiography in the detection and follow-up of congenital pulmonary arteriovenous malformations. Am J Cardiol 68: 1507-1.
15. van Gent MW, Post MC, Snijder RJ, Swaans MJ, Plokker HW, et al. (2009) Grading of pulmonary right-to-left shunt with transthoracic contrast echocardiography: does it predict the indication for embolotherapy? Chest. 2009 May;135 (5):1288-92.
16. Parra J, Bueno J, Zarauza J, Fariñas-Alvarez C, Cuesta JM, et al. (2010) Graded contrast echocardiography in pulmonary arteriovenous malformations. Eur Respir J 35: 1279-85.
17. Zukotynski K, Chan R, Chow C, Cohen J, Faughnan M (2007) Contrast echocardiography grading predicts pulmonary arteriovenous malformations on CT. Chest 132: 18-23. (Pubitemid 47068198)
18. Velthuis S, Buscarini E, van Gent MW, Gazzaniga P, Manfredi G, et al. (2013) Grade of pulmonary right-to-left shunt on contrast echocardiography and cerebral complications; a striking association. Chest 144: 542-8.
19. Moussouttas M, Fayad P, Rosenblatt M, Hashimoto M, Pollak J, et al. (2000) Pulmonary arteriovenous malformations: cerebral ischemia and neurologic manifestations. Neurology 55: 959-64.
20. Shovlin CL, Jackson JE, Bamford KB, Jenkins IH, Benjamin AR, et al. (2008) Primary determinants of ischaemic stroke/brain abscess risks are independent of severity of pulmonary arteriovenous malformations in hereditary haemorrhagic telangiectasia. Thorax 63: 259-66. (Pubitemid 351373723)
21. Cottin V, Chinet T, Lavolé A, Corre R, Marchand E, et al. (2007) Pulmonary arteriovenous malformations in hereditary hemorrhagic telangiectasia: a series of 126 patients. Medicine (Baltimore) 86: 1-17. (Pubitemid 46104915)
22. Guttmacher AE, Marchuk DA, White RI (1995) Hereditary hemorrhagic telangiectasia. New Engl J Med 333: 918-924.
23. Faughnan ME, Palda VA, Garcia-Tsao G, Geisthoff UW, McDonald J, et al. (2011) International guidelines for the diagnosis and management of hereditary haemorrhagic telangiectasia. J Med Genet 48:73-87
24. Shovlin CL (2010) Hereditary haemorrhagic telangiectasia: Pathogenesis, diagnosis and treatment. Blood Rev 24: 203-19.
25. McAllister KA, Grogg KM, Johnson DW, Gallione CJ, Baldwin MA, et al. (1994) Endoglin, a TGF-beta binding protein of endothelial cells, is the gene for hereditary haemorrhagic telangiectasia type 1. Nat Genet 8, 345-351.
26. Johnson DW, Berg JN, Baldwin MA, Gallione CJ, Marondel I, et al. (1996) Mutations in the activin receptor-like kinase 1 gene in hereditary haemorrhagic telangiectasia type 2. Nat Genet 13: 189-95.
27. Gallione CJ, Repetto GM, Legius E, Rustgi AK, Schelley SL, et al. (2004). A combined syndrome of juvenile polyposis and hereditary haemorrhagic telangiectasia associated with mutations in MADH4 (SMAD4). Lancet 2004 Mar 13; 363(9412):852-9. (Pubitemid 38368834)
28. van Gent MW, Post MC, Snijder RJ, Westermann CJ, Plokker HW, et al. (2010) Real prevalence of pulmonary right-to-left shunt according to genotype in patients with hereditary hemorrhagic telangiectasia: a transthoracic contrast echocardiography study. Chest 138: 833-9.
29. Buscarini E, Leandro G, Conte D, Danesino C, Daina E, et al. (2011) Natural history and outcome of hepatic vascular malformations in a large cohort of patients with hereditary hemorrhagic telangiectasia. Dig Dis Sci 56: 2166-78.
30. Krings T, Ozanne A, Chng S, Alvarez H, Rodesch G, et al. (2005) Neurovascular phenotypes in hereditary haemorrhagic telangiectasia patients according to age. Review of 50 consecutive patients aged 1 day-60 years. Neuroradiology 47: 711-20. (Pubitemid 41554551)
31. AAssar OS, Friedman CM, White RI Jr (1991) The natural history of epistaxis in hereditary hemorrhagic telangiectasia. Laryngoscope 101:977-980.
32. Folz BJ, Tennie J, Lippert BM, Werner JA (2005) Natural history and control of epistaxis in a group of German patients with Rendu-Osler-Weber disease. Rhinology 43: 40-46.
33. Kjeldsen AD, Kjeldsen J (2000) Gastrointestinal bleeding in patients with hereditary hemorrhagic telangiectasia. Am J Gastroenterol 95: 415-8. (Pubitemid 30106169)
34. Finnamore H, Le Couteur J, Hickson M, Busbridge M, Whelan K, et al. (2013) Hemorrhage-adjusted iron requirements, hematinics and hepcidin define hereditary haemorrhagic telangiectasia as a model of hemorrhagic iron deficiency. PLoS ONE 8(10):e76516. doi: 10.1371.
35. Roked F, Jackson JE, Fuld J, Basheer FT, Chilvers ER, et al. (2011) Pulmonary thromboemboli modifying the natural history of pulmonary arteriovenous malformations. Am J Resp Crit Care Med 183: 828-9.
36. Yeung M, Khan KA, Antecol DH, Walker DR, Shuaib A (1995) Transcranial Doppler ultrasonography and transesophageal echocardiography in the investigation of pulmonary arteriovenous malformation in a patient with hereditary hemorrhagic telangiectasia presenting with stroke. Stroke 26: 1941-4.
37. Shovlin CL, Guttmacher AE, Buscarini E, Faughnan ME, Hyland RH, et al. (2000) Diagnostic criteria for hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber syndrome). Am J Med Genet 91: 66-7. (Pubitemid 30127562)
38. Shovlin CL, Letarte M (1999) Hereditary haemorrhagic telangiectasia and pulmonary arteriovenous malformations: issues in clinical management and review of pathogenic mechanisms. Thorax 54: 714-29. (Pubitemid 29341410)
39. Remy J, Remy-Jardin M, Wattinne L, Deffontaines C (1992) Pulmonary arteriovenous malformations: evaluation with CT of the chest before and after treatment. Radiology 182: 809-16.
40. Shovlin CL, Wilmshurst P, Jackson JE (2011) Pulmonary arteriovenous malformations and other pulmonary aspects of hereditary haemorrhagic telangiectasia. Eur Respir Mon 54: 218-245
41. Kjeldsen AD, Oxhøj H, Andersen PE, Elle B, Jacobsen JP, et al. (1999) Pulmonary arteriovenous malformations: Screening procedures and pulmonary angiography in patients with hereditary hemorrhagic telangiectasia. Chest 116: 432-439. (Pubitemid 29382129)
42. Blomley M, Harvey C, Hughes J, Heckemann RA, Eckersley RJ, et al. (1999) Can relative signal changes in the intensity of systemic spectral doppler signals after bolus injections of microbubbles measure pulmonary AV shunting noninvasively. Radiology 213: 1145.
43. Shovlin CL, Jackson JE (2004) Pulmonary Arteriovenous Malformations. Ch. 28 in Pulmonary Circulation 2nd Edition, EdPeacock AJ, Rubin LJ, (Edward Arnold, London) 584-599.
44. Shovlin CL, Jackson JE, Hughes JMB (2005) Pulmonary arteriovenous malformations and other pulmonary vascular disorders. Ch. 50 in Murray and Nadel's Textbook of Respiratory Medicine, 4th Edition, eds. Mason RJ, Courtney Broaddus V, Murray JF, Nadel JA. (Elsevier Saunders, Philadelphia) Section L, Pt 50, 1480-1501.
45. Nanthakumar K, Graham AT, Robinson TI, Grande P, Pugash RA, et al. (2001). Contrast echocardiography for detection of pulmonary arteriovenous malformations. Am Heart J 141: 243-6. (Pubitemid 32128729)
46. Feinstein JA, Moore P, Rosenthal DN, Puchalski M, Brook MM (2002) Comparison of contrast echocardiography versus cardiac catheterization for detection of pulmonary arteriovenous malformations. Am J Cardiol. Feb 1; 89(3):281-5.
47. Pilcher J, Blomley M, Shovlin CL, Apsey J Eckersley R, et al. (2001). Detection and quantification of pulmonary arteriovenous shunts using an ultrasound contrast agent. Proc IVth HHT Scientific Conference. 58 (Abstract).
48. An appreciation of Martin Blomley. Reporter. Imperial College London. Available http://www3.imperial.ac.uk/reporter/previousissues/issue16614june2006/ anappreciationofprofessormartinblomley. Accessed 2013 Dec 22.
49. Dutton JA, Jackson JE, Hughes JM, Whyte MK, Peters AM, et al. (1995) Pulmonary arteriovenous malformations: results of treatment with coil embolization in 53 patients. AJR Am J Roentgenol 165: 1119-1125
50. Gupta P, Mordin C, Curtis J, Hughes JM, Shovlin CL, et al. (2002) Pulmonary arteriovenous malformations: effect of embolization on right-to-left shunt, hypoxemia and exercise tolerance in 66 patients. AJR Am J Roentgenol 179: 347-355. (Pubitemid 34785635)
51. Santhirapala V, Williams LC, Tighe H, Jackson JE, Shovlin CL (2013) Effect of iron deficiency on oxygen transport in hypoxaemic patients: implications for haemodynamics and clinical management. Thorax 68 SIII A24 (full manuscript in review, and provided).
52. Shovlin CL, Sulaiman NL, Govani FS, Jackson JE, Begbie ME (2007) Elevated factor VIII in hereditary haemorrhagic telangiectasia (HHT): association with venous thromboembolism. Thromb Haemost. 98: 1031-9. (Pubitemid 350091132)
53. Shovlin CL, Sodhi V, McCarthy A, Lasjaunias P, Jackson JE, et al. (2008) Estimates of maternal risks of pregnancy for women with hereditary haemorrhagic telangiectasia (Osler-Weber-Rendu syndrome): suggested approach for obstetric services. BJOG. 115: 1108-15. (Pubitemid 352000361)
54. Easey AJ, Wallace GM, Hughes JM, Jackson JE, Taylor WJ, et al. (2003) Should asymptomatic patients with hereditary haemorrhagic telangiectasia (HHT) be screened for cerebral vascular malformations? Data from 22,061 years of HHT patient life. J Neurol Neurosurg Psychiatry 74: 743-8. (Pubitemid 36628286)
55. Elphick A, Shovlin CL (2013) Relationships between epistaxis, migraines, and triggers in hereditary hemorrhagic telangiectasia. Laryngoscope Available: http://onlinelibrary.wiley.com/doi/10.1002/lary.24526.
56. Shovlin C, Bamford K, Wray D (2008) Post-NICE 2008: Antibiotic prophylaxis prior to dental procedures for patients with pulmonary arteriovenous malformations (PAVMs) and hereditary haemorrhagic telangiectasia. Br Dent J 205: 531-3.
57. Burtis CA, Ashwood ER, Bruns DE, editors (2006) Tietz textbook of clinical chemistry and molecular diagnostics. 4th ed.St Louis: Elsevier.
58. Shovlin CL, Tighe HC, Davies RJ, Gibbs JS, Jackson JE (2008) Embolisation of pulmonary arteriovenous malformations: no consistent effect on pulmonary artery pressure. Eur Resp J 32: 162-9.
59. Shovlin CL, Angus G, Manning RA, Okoli GN, Govani FS, et al. (2010) Endothelial cell processing and alternatively spliced transcripts of factor VIII: potential implications for coagulation cascades and pulmonary hypertension. PLoS One. 2010 Feb 11;5(2):e9154. doi: 10.1371/journal.pone. 0009154.
60. Livesey JA, Manning RA, Meek JH, Jackson JE, Kulinskaya E, et al. (2012) Low serum iron levels are associated with elevated plasma levels of coagulation factor VIII and pulmonary emboli/deep venous thromboses in replicate cohorts of patients with hereditary haemorrhagic telangiectasia. Thorax 67: 328-33.
61. Valberg LS (1980) Plasma ferritin concentrations: their clinical significance and relevance to patient care. Can Med Assoc J 122: 1240-8.
62. NICE Clinical Knowledge Summaries: Interpreting ferritin levels. Available http://cks.nice.org.uk/anaemia-iron-deficiency#!diagnosisadditional:1/ A-487719-1 Accessed 2014 Feb 10
63. Hart JL, Aldin Z, Braude P, Shovlin CL, Jackson JE (2010) Embolization of pulmonary arteriovenous malformations using the Amplatzer vascular plug: successful treatment of 69 consecutive patients. Eur J Radiology 20: 2663-70.
64. Woods HF, Youdim MBH, Boullin D, Callender S (1977) Monoamine metabolism and platelet function in iron-deficiency anaemia. In: Iron metabolism. In CIBA Foundation Symposium 51 (new series). Amsterdam: Elsevier: pp.227-48.
65. Silva BM, Hosman AE, Devlin HL, Shovlin CL (2013) A questionnaire-based study suggests lifestyle and dietary factors influencing nosebleed severity in hereditary hemorrhagic telangiectasia (HHT). Laryngoscope 123:1092-9.
66. Devlin HL, Hosman AE, Shovlin CL (2013) Antiplatelet and anticoagulant agents in hereditary hemorrhagic telangiectasia. N Engl J Med 368: 876-8.
67. Benjamini Y, Hochberg Y (1995) Controlling the False Discovery Rate: a practical and powerful approach to multiple testing. J Roy Stats Soc (B) 57: 289-300.
68. Clark K, Pyeritz RE, Trerotola SO (2013) Angina pectoris or myocardial infarctions, pulmonary arteriovenous malformations, hereditary haemorrhagic telangiectasia, and paradoxical emboli. Am J Cardiol 112: 731-4
69. Nieswandt B, Pleines I, Bender M (2011) Platelet adhesion and activation mechanisms in arterial thrombosis and ischaemic stroke. J Thromb Haemost 9 Suppl 1:92-104.
70. Furie KL, Kasner SE, Adams RJ, Albers GW, Bush RL, et al. (2011). Guidelines for the prevention of stroke in patients with stroke or transient ischaemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 42: 227-76.
71. Jackson S (2007) The growing complexity of platelet aggregation. Blood 109: 5087-95.
72. Weng LC, Yeh WT, Bai CH, Chen HJ, Chuang SY, et al. (2008) Is ischaemic stroke risk related to folate status or other nutrients correlated with folate intake? Stroke 39: 3152-8.
73. Gillum RF, Sempos CT, Makuc DM, Looker AC, Chien CY, et al. (1996) Serum transferrin saturation, stroke incidence, and mortality in women and men. The NHANES I epidemiologic followup study. Am J Epidemiol 144: 59-68. (Pubitemid 26225288)
74. Bang SM, Lee JO, Kim YJ, Lee KW, Lim S, et al. (2013) Anemia and activities of daily living in the Korean urban elderly population: results from the Korean Longitudinal Study on Health and Aging (KLoSHA). Ann Haematol 92: 59-65.
75. Anand IS, Chandrashekhar Y, Wander GS, Chawla LS (1995) Endothelium-derived relaxing factor is important in mediating the high output state in chronic severe anemia. J Am Coll Cardiol 25: 1402-7.
76. Porter WB, Watson JG (1953) The Heart in Anemia. Circulation 8: 111-116.
77. Hébert PC, Van der Linden P, Biro G, Hu LQ (2004) Physiologic aspects of anemia. Crit Care Clin 20: 187-212. (Pubitemid 38596811)
78. Van de Pette JE, Guthrie DL, Pearson TC (1986) Whole blood viscosity in polycythaemia: the effect of iron deficiency at a range of haemoglobin and packed cell volumes. Br J Haematol 63: 369-75. (Pubitemid 16085872)
79. Hao Z, Liu M, Counsell C, Wardlaw JM, Lin S, et al. (2012) Fibrinogen depleting agents for acute ischaemic stroke. Cochrane Database Syst Rev 3: CD000091.
80. Uchiyama S, Ozaki Y, Satoh K, Kondo K, Nishimaru K (2007) Effect of sarpogrelate, a 5-HT(2A) antagonist, on platelet aggregation in patients with ischaemic stroke: clinical-pharmacological dose-response study. Cerebrovasc Dis 24: 264-70. (Pubitemid 47295595)
81. Ono K, Arimoto H, Shirotani T (2012) Correlation between increased platelet ADP aggregability and silent brain infarcts. Brain Nerve 64: 185-9.
82. Hara K, Hirowatari Y, Yoshika M, Komiyama Y, Tsuka Y, et al. (2004) The ratio of plasma to whole-blood serotonin may be a novel marker of atherosclerotic cardiovascular disease. J Lab Clin Med 144: 31-37.
83. Shinohara Y, Nishimaru K, Sawada T, Terashi A, Handa S, et al. (2008) Sarpogrelate-Aspirin Comparative Clinical Study for Efficacy and Safety in Secondary Prevention of Cerebral Infarction (S-ACCESS): A randomized, double-blind, aspirin-controlled trial. Stroke 39: 1827-33.
84. Coupland C, Dhiman P, Morriss R, Arthur A, Barton G, et al. (2011) Antidepressant use and risk of adverse outcomes in older people: population based cohort study. BMJ 343: d4551.