Anaemia and iron deficiency in clinical practice:
from cardiology to gastroenterology and beyond

Česká verzia

Authors: Richard Češka
Authors place of work: Centrum preventivní kardiologie III. interní kliniky 1. LF UK a VFN Praha, přednosta prof. MUDr. Štěpán Svačina, DrSc., MBA
Published in the journal: Vnitř Lék 2014; 60(12): 1033-1039
Category: 70. birthday prof. MUDr. Michael Aschermann, DrSc., FESC, FACC

Summary

Anaemia is one of the most common diseases. Worldwide affects up to 25% of the population. Anaemia with iron deficiency (Fe) is the leading one. It is not surprising that iron deficiency mainly affects women. Generally, anaemia is one of the major problems in every department of internal medicine. There is no ambition to provide a comprehensive review of the diagnosis and treatment of anaemia. The aim is to point out the common (but sometimes neglected) facts from daily practice in internal department and on the other hand, to highlight the news in the treatment focusing on parenteral Fe.

The importance of anaemia at the department of internal medicine.
Mentioned above, anaemia is very frequent in internal medicine. Especially, it is anaemia of Fe deficiency and anaemia of chronic disease. Mostly elderly and polymorbid patients (often with one dominant, sometimes cryptogenic disease) suffer from anaemia. I am concern about the fact that anaemia is often seen only as a sign of other disease and usually is not the target of diagnostic and therapeutic efforts.

Diagnosis and treatment.
The internal department physician is responsible for patient care, but cooperates with haematologist in case of severe anaemia in diagnostic and therapeutic process. Basic examination contains analysis of Fe, ferritin, transferrin, circulating serum transferrin receptors or other parameters. Of course, the focus in iron deficiency anaemia is on its possible loss or in case of chronic disease anaemia on primary disease.

Notes to Fe treatment.
If the patient has iron deficiency the Fe treatment is often indicated (after finding the cause). Iron is administered orally in most cases. There are several situations when parenteral Fe is not only preferable, but also represents the only therapeutic option. Currently, the best evidence for the positive effects is observed in parenterally administered Fe ferric carboxymaltose, Ferinject.

Parenteral administration of Fe in gastroenterology.
Gastorenterology is a common field for the use of Fe administration. The losses in the GIT are frequent as well as malabsorption of Fe in several gastrointestinal diseases. A typical example may be inflammatory bowel disease, especially Crohn´s disease. Not only case reports demonstrate the positive effect of ferric carboxymaltose in Crohn´s disease.

Parenteral administration of Fe in cardiology.
Recently published work (multicentric randomized controlled double-blinde trial) CONFIRM HF have proved that administration of ferric carboxymaltose in heart failure patients have improved their functional ability, NYHA stratification and quality of life. The pilot studies performed before resulted positively and CONFIRM HF only confirmed their conclusions.

Quality of life – neglected parameter.
Conclusions of CONFIRM HF introduce the improved quality of life as one of the main result. Unfortunately, it is a parameter (subjective, difficult to objectify) which doesn´t have such importance as endpoint – indicator of intervention trials. It is shown that treatment of anaemia is important in chronic fatigue (especially women) and affects quality of life. Improvement in symptoms of fatigue has been demonstrated after administration of 1000 mg of ferric carboxymaltose. Fe treatment improves quality of life in anaemic oncology patients as well.

Key words:
anaemia – CONFIRM HF – Fe – Ferinject – ferric carboxymaltose – heart failure – iron deficiency

Zdroje

1. Andrews NC Disorders of iron metabolism. N Engl J Med 1999; 341: 1986–1995.

2. Brunner AB, Joffe A, Dugan AK et al. Randomized study of cognitive effects of iron supplementation in non-anaemic iron-deficient adolescent girls. Lancet 1996; 348: 992–996.

3. Bui AL, Horwich TB, Fonarow GC Epidemiology and risk profile of heart failure. Nat Rev Cardiol 2011; 8: 30–41.

4. Cook JD, Lynch SR The liabilities of iron deficiency. Blood 1986; 68: 803–809.

5. Čermák J, Trněný M et al. Anémie. In: Češka R et al. Interna. Praha: Triton 2010, 656–669.

6. Čermák J, Brabec V Klinický význam vyšetření hladiny cirkulujících transferinových receptorů v séru. Vnitř Lék 1999; 45: 468–472.

7. Čermák J, Brabec V Transferrin receptor – ferritin index: a useful parameter in differential diagnosis of iron deficiency and hyperplastic erythropoiesis. Eur J Haematol 1998; 61: 210–212.

8. Datz C, Felder TK, Niederseer D et al. Iron homeostasis in the metabolic syndrome. Eur J Clin Invest 2013; 43: 215–224.

9. Erslev AJ Anemia of chronic disease, s. 481–487. In: Beutler E, Lichtman MA, Coller BS et al. Williams hematology. 6th edit. New York: Mc Graw-Hill 2001, 1941 s.

10. 10 .Evstatiev R et al. Gastroenterology 2011;141(3):846–853

11. Foerster J et al.: Wintrobe’s clinical hematology. 10th edit. Philadelphia: Lea Febiger 1998, 2763 s.

12. Gardner LB, Benz jr. EJ Anemia chronic diseases, s. 383–388. In: Hoffman R, Benz EJ, Shattil SJ et al. Hematology. Basic principles and practice. 3rd edit. New York: Churchill Livingstone 2000, 2584 s.

13. Gasche C, Chapter 42, section 6 Gastroenterology/inflammatory bowel disease: anaemia of chronic disease

14. Gasche C et al. Inflamm Bowel Dis 2007;13(12):1545–1553;

15. Geisser P. Port J Nephrol Hypert 2009;23:11–6

16. Hoekstra T, Jaarsma T, van Veldhuisen DJ et al. Quality of life and survival in patients with heart failure. Eur J Heart Fail 2013; 15: 94–102.

17. Holyoke TL, Stott DJ, Mc Kay PJ et al. Use of plasma ferritin concentration to diagnose iron deficiency in elderly patients. J Clin Pathol 1993; 48: 857–860.

18. Chrobák L Přínos laboratoře k diferenciální diagnostice anémií. Hematológia transfuziológia 2000; 10: 163–173.

19. Chrobák L Mikrocytární a hypochromní anémie. Vnitř Lék 2001; 47: 166–174.

20. Jankowska EA, Kasztura M, Sokolski M et al. Iron deficiency defined as depleted iron stores accompanied by unmet cellular iron requirements identifies patients at the highest risk of death after an episode of acute heart failure. Eur Heart J 2014 (Epub ahead of print) (13 Jun)

21. Kilpatrick ZM, Katz J Occult celiac disease as a cause of iron deficiency anaemia. J Amer Med Ass 1969; 208: 999–1001.

22. Kasner M, Aleksandrov AS, Westermann D et al. Functional iron deficiency and diastolic function in heart failure with preserved ejection fraction. Int J Cardiol 2013; 168: 4652–4657.

23. Klip IT, Comin-Colet J, Voors AA et al. Iron deficiency in chronic heart failure: an international pooled analysis. Am Heart J 2013; 165: 575–582.

24. Kulnigg S et al. Am J Gastroenterol 2009;104(6):1460–1467

25. Lee GR, Forster J, Lukes J et al. Iron deficiency and iron deficiency anaemia. In: Wintrobe’s Clinical Hematology. Baltimore: Williams & Wilkins 1998, 979–1009.

26. Means jr. RT The anemia of chronic disorders, s.1011–1021. In: Lee, G.R., Bithell, T.C., XXXXX

27. Poniklowski P. et al. CONFIRM-HF ferric Carboxymaltose evaluation on performance in patients with iron deficiency in combination with chronic heart failure. Eur Heart J doi 10 (eurheart) 1093

28. Ponikowski P, van Veldhuisen DJ, Colet J et al. Rationale and Design of the CONFIRM-HF Study: a Double-Blind, Randomized, Placebo-Controlled Study to Assess the Effects of Intravenous Ferric Carboxymaltose on Functional Capacity in Patients with Chronic Heart Failure and Iron Deficiency. ESC Heart Fail 2014 (Epub ahead of pub).

29. Okonko DO, Mandal AKJ, Missouris CG et al. Disordered iron homeostasis in chronic heart failure: prevalence, predictors, and relations to anemia, exercise capacity, and survival. J Am Coll Cardiol 2011; 58: 1241–1251.

30. Spivak JL The blood in systemic disorders. Lancet 2000; 355: 1707–1712.

31. Voglová J, Chrobák L, Radochová D et al. Anémie z nedostatku železa u dospívajících chlapců. Prakt Lék 1993; 73: 92–98.

32. Geisser P. The pharmacology and safety prolife of ferric carboxymaltose (Ferrinject): structure/reactivity relationship if iron preparations. Port J Nephrol Hypert 2009; 23(1):11–16.

33. Gasche C, Berstad A, Befrits R et al. Guidelines on the diagnosis and management of iron deficiency and anemia in inflammatory bowel diseases. Inflamm Bowel Dis 2007; 13(12): 1545–1553.

34. Evstatiev R, Marteau P, Iqbal T et al. FERGIcor, a randomized controlled trial on ferric carboxymaltose for iron deficiency anemia in inflammatory bowel disease.Gastroenterology 2011;141(3):846–853.

35. Kulnigg S, Teischinger L, Dejaco C et al. Rapid recurrence of IBD-associated anemia and iron deficiency after intravenous iron sucrose and erythropoietin treatment. Am J Gastroenterol 2009; 104(6): 1460–1467.

36. Juenger J, Schellberg D, Kraemer S et al. Health related quality of life in patients with congestive heart failure: comparison with other chronic diseases and relation to functional variables. Heart 2002; 87(3): 235–241.

37. Huch E, Schaefer R. Iron deficiency and iron deficiency anaemia. Thieme: Stuttgart 2006. ISBN 9783131337610.

38. Hentze MW, Muckenthaler MU, Galy B et al. Two to tango: regulation of mammalian iron metabolism. Cell 2010; 142(1): 24–38.