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

Volumn 67, Issue 4, 2012, Pages 328-333

  Livesey, John A ^a,b   Manning, Richard A ^c   Meek, John H ^d   Jackson, James E ^d   Kulinskaya, Elena ^e   Laffan, Michael A ^b,c   Shovlin, Claire L ^b,d  

^a IMPERIAL COLLEGE SCHOOL OF MEDICINE   (United Kingdom)

^b IMPERIAL COLLEGE LONDON   (United Kingdom)

^c HAMMERSMITH HOSPITAL   (United Kingdom)

^d IMPERIAL COLLEGE HEALTHCARE NHS TRUST   (United Kingdom)

^e UNIVERSITY OF EAST ANGLIA   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

BIOLOGICAL MARKER; BLOOD CLOTTING FACTOR 8; FERRITIN; IRON; VON WILLEBRAND FACTOR;

ADULT; AGE DISTRIBUTION; ARTICLE; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DEEP VEIN THROMBOSIS; DISEASE ASSOCIATION; EPISTAXIS; FEMALE; FERRITIN BLOOD LEVEL; GASTROINTESTINAL HEMORRHAGE; HIGH RISK POPULATION; HUMAN; INCIDENCE; INFLAMMATION; IRON BLOOD LEVEL; IRON DEFICIENCY; IRON DEFICIENCY ANEMIA; LUNG EMBOLISM; MAJOR CLINICAL STUDY; MALE; NUCLEOTIDE SEQUENCE; PATHOPHYSIOLOGY; PRIORITY JOURNAL; RISK FACTOR; TELANGIECTASIA;

EID: 84858797729     PISSN: 00406376     EISSN: 14683296     Source Type: Journal    
DOI: 10.1136/thoraxjnl-2011-201076     Document Type: Article

References (36)

1. Kyrle PA, Rosendaal FR, Eichinger S. Risk assessment for recurrent venous thrombosis. Lancet 2010;376:2032-9.
2. Anderson FA Jr, Wheeler HB, Goldberg RJ, et al. A population-based perspective of the hospital incidence and case-fatality rates of deep vein thrombosis and pulmonary embolism. The Worcester DVT Study. Arch Intern Med 1991;151:933-8.
3. Shovlin CL. Hereditary haemorrhagic telangiectasia: pathogenesis, diagnosis and treatment. Blood Rev 2010;24:203-19.
4. Shovlin CL, Sulaiman NL, Govani FS, et al. Elevated factor VIII in hereditary haemorrhagic telangiectasia (HHT): association with venous thromboembolism. Thromb Haemost 2007;98:1031-9. (Pubitemid 350091132)
5. Kraaijenhagen RA, in't Anker PS, Koopman MM, et al. High plasma concentration of factor VIIIc is a major risk factor for venous thromboembolism. Thromb Haemost 2000;83:5-9.
6. Kyrle PA, Minar E, Hirschl M. High plasma levels of FVIII and the risk of recurrent venous thromboembolism. N Engl J Med 2000;343:457-62. (Pubitemid 30646484)
7. Smith NL, Chen MH, Dehghan A, et al. Novel associations of multiple genetic loci with plasma levels of factor VII, factor VIII, and von Willebrand factor: the CHARGE (Cohorts for Heart and Aging Research in Genome Epidemiology) Consortium. Circulation 2010;121:1382-92.
8. Luxembourg B, Schmitt J, Humpich M, et al. Intrinsic clotting factors in dependency of age, sex, body mass index, and oral contraceptives: definition and risk of elevated clotting factor levels. Blood Coagul Fibrinolysis 2009;20:524-34.
9. Begbie M, Notley C, Tinlin S, et al. The factor VIII acute phase response requires the participation of NFkappaB and C/EBP. Thromb Haemost 2000;84:216-22. (Pubitemid 30601466)
10. Shovlin CL, Guttmacher AE, Buscarini E, et al. Diagnostic criteria for hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber syndrome). Am J Med Genet 2000;91:66-7. (Pubitemid 30127562)
11. Burtis CA, Ashwood ER, Bruns DE, eds. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. 4th edn. St Louis: Elsevier, 2006.
12. Shovlin CL, Jackson JE, Bamford KB, et al. Primary determinants of ischaemic stroke/ brain abscess risks are independent of severity of pulmonary arteriovenous malformations in hereditary haemorrhagic telangiectasia. Thorax 2008;63:259-66. (Pubitemid 351373723)
13. Motulsky HJ, Christopoulos A. Fitting models to biological data using linear and non linear regression. A practical guide to curve fitting. San Diego CA: GraphPad Software Inc., 2003. www.graphpad.com
14. Ganz T. Hepcidin and iron regulation, 10 years later. Blood 2011;117:4425-33.
15. Campillos M, Cases I, Hentze MW, et al. SIREs: searching for iron-responsive elements. Nucleic Acids Res 2010;38(Suppl. W):360-7.
16. Shovlin CL, Angus G, Manning RA, et al. Endothelial cell processing and alternatively spliced transcripts of factor VIII. Potential implications for coagulation cascades and pulmonary hypertension. PLOS One 2010;5:e9154.
17. Shovlin CL, Wilmshurst P, Jackson JE. Pulmonary arteriovenous malformations and other pulmonary aspects of HHT. Eur Respir Mon 2011;54:218-45.
18. 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 study. J Neurol 2007;254:729-34. (Pubitemid 47012446)
19. Sundström A, Seaman H, Kieler H, et al. The risk of venous thromboembolism associated with the use of tranexamic acid and other drugs used to treat menorrhagia: a caseecontrol study using the General Practice Research Database. BJOG 2009;116:91-7.
20. Adoh A, Kouame AN, Kouassi YF, et al. Etiological factors of deep vein thromboses in the limbs of Black African subjects. Med Trop (Mars) 1992;52:131-7.
21. Malhotra S, Garg SK, Khullar GK, et al. Kinetics of two different iron formulations and their effect on diurnal variation of serum iron levels. Methods Find Exp Clin Pharmacol 2004;26:417-20. (Pubitemid 39079108)
22. Hutchinson C, Conway RE, Bomford A, et al. Post-prandial iron absorption in humans: comparison between HFE genotypes and iron deficiency anaemia. Clin Nutr 2008;27:258-63.
23. http://cks.nhs.uk/anaemia-iron-deficiency/management/scenario-diagnosis/ investigations/interpreting-ferritin-levels (accessed 4 Nov 2011).
24. Roked F, Jackson JE, Fuld J, et al. Pulmonary thromboemboli modifying the natural history of pulmonary arteriovenous malformations. Am J Respir Crit Care Med 2011;183:828-9.
25. Kuku I, Kaya E, Yologlu S, et al. Platelet counts in adults with iron deficiency anemia. Platelets 2009;20:401-5.
26. Faughnan ME, Palda VA, Garcia-Tsao G, et al. International guidelines for the diagnosis and management of hereditary hemorrhagic telangiectasia. J Med Genet 2011;48:73-87.
27. Confidential enquiry into maternal deaths (CEMACH). Saving Mothers Lives 2003-2005 (Full Report). http://cemach.interface-test.com (accessed 29 Nov 2011).
28. McLean E, Cogswell M, Egli I, et al. Worldwide prevalence of anaemia, WHO Vitamin and Mineral Nutrition Information System, 1993-2005. Public Health Nutr 2009;12:444-54.
29. Centers for Disease Control and Prevention. Recommendations to prevent and control iron deficiency in the United States. MMWR Recomm Rep 1998;47:1-36.
30. Jacquemin M, Neyrinck A, Hermanns MI, et al. FVIII production by human lung microvascular endothelial cells. Blood 2006;108:515-17. (Pubitemid 44061350)
31. Shahani T, Lavend'homme R, Luttun A, et al. Activation of human endothelial cells from specific vascular beds induces the release of a FVIII storage pool. Blood 2010;115:4902-9.
32. Bonderman D, Turecek PL, Jakowitsch J, et al. High prevalence of elevated clotting factor VIII in chronic thromboembolic pulmonary hypertension. Thromb Haemost 2003;90:372-6. (Pubitemid 37138760)
33. Wolf M, Boyer-Neumann C, Parent F, et al. Thrombotic risk factors in pulmonary hypertension. Eur Respir J 2000;15:395-99. (Pubitemid 30085971)
34. Ruiter G, Lankhorst S, Boonstra A, et al. Iron deficiency is common in idiopathic pulmonary arterial hypertension. Eur Respir J 2011;37:1386-91.
35. Soon E, Treacy CM, Toshner MR, et al. Unexplained iron deficiency in idiopathic and heritable pulmonary arterial hypertension. Thorax 2011;66:326-32.
36. Rhodes CJ, Howard LS, Busbridge M, et al. Iron deficiency and raised hepcidin in idiopathic pulmonary arterial hypertension: clinical prevalence, outcomes, and mechanistic insights. J Am Coll Cardiol 2011;58:300-9.