Aggiornamento monografico
Le microcitosi nel bambino: classificazione e approccio diagnostico
MICROCYTOSIS: CLASSIFICATION AND DIAGNOSIS
ANTONELLA SCIOTTO, VALERIA FURIA, SILVANA ESTER MUNDA
Dipartimento di Ematologia e Oncologia Pediatrica, Università di Catania
Febbraio 2001 - pagg. 87 -93
Abstract
The Authors provide an overview of microcytic anemias. Causes of microcytic anemia include
a wide variety of diseases, the most common being iron-deficiency, impaired haemoglobin
synthesis, sideroblastic anemias and anemias due to chronic disease. Other less common
causes are copper deficiency, lead poisoning and haemosiderosis. A classification of
the main microcytic anemias is provided and a diagnostic approach to microcytosis, with
and without anemia, based on RDW and MCV is suggested.
Parole chiave
Suggerite dall'AI
Classificazione MeSH
Bibliografia
1. Paterakis GS, Laoutaris NP, Alexia SV,
Siourounis PV, Stamulakatou AK, Premetis
EE, Sakellariou Ch, Terzoglou GN, Papassotiriou
IG, Loukopoulos D. The effecte of red
cell shape on the measurement of red cell volume.
A proposed method for the comparative
assessment of this effect among various
haematology analysers. Clin Lab Haemat
1994;16:235.
2. Bessman JD, Gilmer PR Jr, et al. Improved classification of anemias by MCV and RDW. Am J Clin Pathol 1983;80:322.
3. Lee GR. Microcytosis and the anemias associated with impaired hemoglobin synthesis. In: Lee GR, Githell TC, Foerster J, Athens JW, Lukens JN (eds). Wintrobe’s Clinic Hematology. Philadelphia: Lea & Febiger, 1993:791.
4. Oski FA, Brugnara C, Nathan DG. A diagnostic approach to the anemic patient.5th edition. In: Hematology of infancy and childhood. Philadelphia: WB Saunders Co, 1998:375.
5. Lee GR. Iron deficiency and iron-deficiency anemia. In: Lee GR, Githell TC, Foerster J, Athens JW, Lukens JN (eds). Wintrobe’s Clinic Hematology. Philadelphia: Lea & Febiger, 1993:808.
6. Van Zeben D, et al. Evaluation of microcytosis using serum ferritin and red blood cell distribution width. Eur J Haematol 1990; 44:105.
7. Lee GR. The anemia of chronic disease. Semin Hematol 1983;20:61.
8. Abshire TC, Reeves JD. Anemia of inflammation in children. J Pediatr 1983;103:868.
9. Koerper MA, Stempel DA, et al. Anemia in patient with juvenile rheumatoid arthritis. J Pediatr 1978;92:930.
10. Means RT, Dessypris EN, Krautz SB. Inhibition of human colony-forming-unit erytroid by tumor necrosis factor requires accessory cells. J Clin Invest 1990;86:538.
11. Ludwig H and Fritz E. Anemia in Cancer Patients. Seminars in Oncology, Vol 25, No 3, Suppl. 7 (June), 1998:2-6.
12. Chitambar CR, Zivkovic Z. Inhibition of hemoglobin production by transferrin-gallium. Blood 1987;69:144.
13. Brugnara C, Chambers LA, Malynn E, Goldberg MA, Kruskall MS. Red blood cell regeneration induced by subcutaneous recombinant erythropoietin:iron-deficient erythropoiesis in iron-replete subjects. Blood 1993;81:956-64.
14. Fleming AF. Iron deficiency in the tropics. Clin Haematol 1982;11:365.
15. Barabino A, Dufour C, Marino CE, Claudiani F, De Alessandri A. Unexplained refractory iron-deficiency anemia associated with Helicobacter pylori gastric infection in children: further clinical evidence. J Pediatr Gastroenterol Nutr 1999;28:116-9.
16. Tugal O, Jacobson R, Berezin St, Foreman S, Berenzin Si, Brudniki A, Godine L, Davidian MM, Jayabose S, Escobedo V. Recurrent benign intracranial hypertension due to iron deficiency anemia. Am J Pediatr Hematol Oncol 1994;16(3):266-70.
17. Kuhn MJ. Idiopathic pulmonary hemosiderosis: the importance of a chest radiograph in children with unexplained anemia. Mt Sinai J Med (NY) 1985;52:358.
18. Rees AJ. Pulmonary injury caused by antibasement membrane antibodies. Semin Respir Med 1984;5:264.
19. Turner N, Mason PJ, Brown R, Fox M, Povey S, Rees A, Pusey CD. Molecular cloning of the human Goodpasture antigen demonstrates it to be the alpha-3 chain of type IV collagen. J Clin Invest 1992;89:592-601.
20. Kosnai I, Kuitunen P, Siimes MA. Iron deficiency in children with coeliac disease on treatment with gluten-free diet. Arch Dis Child 1979;54:375.
21. Goya N, Miyazaki S, Kodate S, Ishio B. A family of congenital atransferrinemia. Blood 1972;40:239.
22. Hartman KR, Baker JA. Microcytic anemia with iron malabsorption: an inherited disorder of iron metabolism. Am J Hematol 1996;51:269.
23. Su MA, Trenor CC, Fleming JC, Fleming MD, Andrews NC. The G185R mutation disrupt function of the iron transporter Nramp2. Blood 1998;92(6):2517-63.
24. Shahidi NT, Nathan DG, Diamond LK. Iron deficiency anemia associated with an error of iron metabolism in two siblings. J Clin Invest 1964;43:510.
25. Larrick JW, Hyman ES: Acquired iron deficiency anemia caused by an antibody against the transferrin receptor. N Engl J Med 1984;311:214.
26. Weatherall DJ. The thalassemias. In: Beutler W (ed). Hematology. New York: Mc Graw Hill, 1995:581-615.
27. Rund D, Filon D, Strauss N, Rachmilewitz EA, Oppenheim A. Mean corpuscolar volume of etherozygotes for ß-thalassemia correlates with the severity of mutations. Blood 1992; 79:238-43.
28. Rosatelli C, Leoni GB, Tuveri T, Scalas MT, Mosca A, Galanello R, Gasperini D, Cao A. Heterozygous ß-thalassemia: relationship between the hematological phenotype and the type of ß-thalassemia mutation. Am J Haem 1992;39:1-4.
29. Fairbanks VF, et al. Homozygous hemoglobin E mimics beta-thalassemia minor without anemia or hemolysis: Hematologic functional and biosynthetic studies of first North American cases. Am J Hematol 1980;8:109.
30. Rees DC, Styles L, Vichinsky EP, Clegg JB, Weatherall DJ. The hemoglobin E syndromes. Ann N Y Acad Sci 1998;850:334-43.
31. Fabry ME, et al. Some aspects of the pathophysiology of homozygous Hb CC erythrocytes. J Clin Invest 1981;67:1284.
32. Dover GJ, Platt OS. Sickle cell disease. In: Nathan DG, Orkin SH (eds). Hematology of infancy and childhood, 5a ed. Philadelphia: WB Saunders Co, 1998.
33. Weatherall DJ, Clegg JB. Hereditary persistence of fetal hemoglobin. Br J Haematol 1975;29:191.
34. Bridges KR, Andrews NC. Disorders of iron metabolism and sideroblastic anemia. In: Nathan DG, Orkin SH (eds). Hematology of infancy and childhood, 5a ed.,Philadelphia: WB Saunders Co, 1998:423-61.
35. Cotter PD, May A, Fitzsimons EJ, Houston T, Woodcock BE, al-Sabah AI, Wong L, Bishop DF. Late-onset X-Linked sideroblastic anemia. Missense mutations in the erythroid delta-aminolevulinate synthase (ALAS2) gene in two pyridoxine-responsive patients initially diagnosed with acquired refractory anemia and ringed sideroblasts. J Clin Invest 1995; 96(4):2090.
36. Touam M, et al. Aluminium-induced, reversible microcytic anemia in chronic renal failure: clinical and experimental studies. Clin Nephrol 1983;19:285.
37. Schroeder TM, Caspers ML. Kinetics of aluminium induced inhibition of delta-aminolevulinic acid dehydratase in vitro. Biochem Pharmacol 1996;52:927-31.
38. Caramelo CA, Cannata JB, Rodeles MR, Fernandez JL, Mosquera JR, Monzu B, Outeirino J, Blum J, Andrea C, Lopez FA, et al. Mechanism of aluminum induced microcytosis: lesson from accidental aluminum intoxication. Kidney Int 1995;47:164-8.
39. Danks DM. Copper deficiency in humans. Ann Rev Nutr 1988;8:235.
40. Williams DM. Copper deficiency in humans. Semin Hematol 1983;20:118.
41. Castillo Duran C, Uauy R. Copper deficiency impairs growth of infants recovering from malnutrition. Am J Clin Nutr 1988; 47:710.
42. Levy Y, Zeharia A, et al. Copper deficiency in infants fed cow milk. J Pediatr 1985; 106:786.
43. Menkes JH, Alter M, et al. A sex-linked recessive disorders with ritardation of growth, peculiar hair and focal cerebral and cerebellar degeneration. Pediatrics 1962; 29:764.
44. Vulpe C, Levinson B, et al. Isolation of a candidate gene for Menkes disease and evidence that it encodes a copper transporting ATPase. Nat Genet 1993;3:7.
45. Bull PC, Thomas GR, et al. The Wilson’s disease gene is a putative copper transporting P-type ATPase similar to the Menkes gene. Nat Genet 1993;5:327.
46. Yoshida K, Furiatha K, Takeda S, et al. A mutation in the ceruloplasmin gene is associated with systemic hemosiderosis in humans. Nat Genet 1995;9:267-72.
47. Harris ZL, Takahashi Y, Miyajima H, Serizawa M, MacGillivray RTA, Gitlin JD. Aceruloplasminemia: a molecular of this disordes of iron metabolism. Proc Natl Acad Sci USA 1995;92:2539-43.
48. Sergio Piomelli. Lead poisoning. In: Nathan DG, Orkin SH (eds). Hematology of infancy and childhood, 5a ed., Philadelphia: W.B. Saunders Co, 1998:480.
49. Shigern Sassa, Atallah Kappas. The porphyrias. In: Nathan DG, Orkin SH (eds). Philadelphia: Hematology of infancy and childhood, 5a ed., WB Saunders Co, 1998: 463.
2. Bessman JD, Gilmer PR Jr, et al. Improved classification of anemias by MCV and RDW. Am J Clin Pathol 1983;80:322.
3. Lee GR. Microcytosis and the anemias associated with impaired hemoglobin synthesis. In: Lee GR, Githell TC, Foerster J, Athens JW, Lukens JN (eds). Wintrobe’s Clinic Hematology. Philadelphia: Lea & Febiger, 1993:791.
4. Oski FA, Brugnara C, Nathan DG. A diagnostic approach to the anemic patient.5th edition. In: Hematology of infancy and childhood. Philadelphia: WB Saunders Co, 1998:375.
5. Lee GR. Iron deficiency and iron-deficiency anemia. In: Lee GR, Githell TC, Foerster J, Athens JW, Lukens JN (eds). Wintrobe’s Clinic Hematology. Philadelphia: Lea & Febiger, 1993:808.
6. Van Zeben D, et al. Evaluation of microcytosis using serum ferritin and red blood cell distribution width. Eur J Haematol 1990; 44:105.
7. Lee GR. The anemia of chronic disease. Semin Hematol 1983;20:61.
8. Abshire TC, Reeves JD. Anemia of inflammation in children. J Pediatr 1983;103:868.
9. Koerper MA, Stempel DA, et al. Anemia in patient with juvenile rheumatoid arthritis. J Pediatr 1978;92:930.
10. Means RT, Dessypris EN, Krautz SB. Inhibition of human colony-forming-unit erytroid by tumor necrosis factor requires accessory cells. J Clin Invest 1990;86:538.
11. Ludwig H and Fritz E. Anemia in Cancer Patients. Seminars in Oncology, Vol 25, No 3, Suppl. 7 (June), 1998:2-6.
12. Chitambar CR, Zivkovic Z. Inhibition of hemoglobin production by transferrin-gallium. Blood 1987;69:144.
13. Brugnara C, Chambers LA, Malynn E, Goldberg MA, Kruskall MS. Red blood cell regeneration induced by subcutaneous recombinant erythropoietin:iron-deficient erythropoiesis in iron-replete subjects. Blood 1993;81:956-64.
14. Fleming AF. Iron deficiency in the tropics. Clin Haematol 1982;11:365.
15. Barabino A, Dufour C, Marino CE, Claudiani F, De Alessandri A. Unexplained refractory iron-deficiency anemia associated with Helicobacter pylori gastric infection in children: further clinical evidence. J Pediatr Gastroenterol Nutr 1999;28:116-9.
16. Tugal O, Jacobson R, Berezin St, Foreman S, Berenzin Si, Brudniki A, Godine L, Davidian MM, Jayabose S, Escobedo V. Recurrent benign intracranial hypertension due to iron deficiency anemia. Am J Pediatr Hematol Oncol 1994;16(3):266-70.
17. Kuhn MJ. Idiopathic pulmonary hemosiderosis: the importance of a chest radiograph in children with unexplained anemia. Mt Sinai J Med (NY) 1985;52:358.
18. Rees AJ. Pulmonary injury caused by antibasement membrane antibodies. Semin Respir Med 1984;5:264.
19. Turner N, Mason PJ, Brown R, Fox M, Povey S, Rees A, Pusey CD. Molecular cloning of the human Goodpasture antigen demonstrates it to be the alpha-3 chain of type IV collagen. J Clin Invest 1992;89:592-601.
20. Kosnai I, Kuitunen P, Siimes MA. Iron deficiency in children with coeliac disease on treatment with gluten-free diet. Arch Dis Child 1979;54:375.
21. Goya N, Miyazaki S, Kodate S, Ishio B. A family of congenital atransferrinemia. Blood 1972;40:239.
22. Hartman KR, Baker JA. Microcytic anemia with iron malabsorption: an inherited disorder of iron metabolism. Am J Hematol 1996;51:269.
23. Su MA, Trenor CC, Fleming JC, Fleming MD, Andrews NC. The G185R mutation disrupt function of the iron transporter Nramp2. Blood 1998;92(6):2517-63.
24. Shahidi NT, Nathan DG, Diamond LK. Iron deficiency anemia associated with an error of iron metabolism in two siblings. J Clin Invest 1964;43:510.
25. Larrick JW, Hyman ES: Acquired iron deficiency anemia caused by an antibody against the transferrin receptor. N Engl J Med 1984;311:214.
26. Weatherall DJ. The thalassemias. In: Beutler W (ed). Hematology. New York: Mc Graw Hill, 1995:581-615.
27. Rund D, Filon D, Strauss N, Rachmilewitz EA, Oppenheim A. Mean corpuscolar volume of etherozygotes for ß-thalassemia correlates with the severity of mutations. Blood 1992; 79:238-43.
28. Rosatelli C, Leoni GB, Tuveri T, Scalas MT, Mosca A, Galanello R, Gasperini D, Cao A. Heterozygous ß-thalassemia: relationship between the hematological phenotype and the type of ß-thalassemia mutation. Am J Haem 1992;39:1-4.
29. Fairbanks VF, et al. Homozygous hemoglobin E mimics beta-thalassemia minor without anemia or hemolysis: Hematologic functional and biosynthetic studies of first North American cases. Am J Hematol 1980;8:109.
30. Rees DC, Styles L, Vichinsky EP, Clegg JB, Weatherall DJ. The hemoglobin E syndromes. Ann N Y Acad Sci 1998;850:334-43.
31. Fabry ME, et al. Some aspects of the pathophysiology of homozygous Hb CC erythrocytes. J Clin Invest 1981;67:1284.
32. Dover GJ, Platt OS. Sickle cell disease. In: Nathan DG, Orkin SH (eds). Hematology of infancy and childhood, 5a ed. Philadelphia: WB Saunders Co, 1998.
33. Weatherall DJ, Clegg JB. Hereditary persistence of fetal hemoglobin. Br J Haematol 1975;29:191.
34. Bridges KR, Andrews NC. Disorders of iron metabolism and sideroblastic anemia. In: Nathan DG, Orkin SH (eds). Hematology of infancy and childhood, 5a ed.,Philadelphia: WB Saunders Co, 1998:423-61.
35. Cotter PD, May A, Fitzsimons EJ, Houston T, Woodcock BE, al-Sabah AI, Wong L, Bishop DF. Late-onset X-Linked sideroblastic anemia. Missense mutations in the erythroid delta-aminolevulinate synthase (ALAS2) gene in two pyridoxine-responsive patients initially diagnosed with acquired refractory anemia and ringed sideroblasts. J Clin Invest 1995; 96(4):2090.
36. Touam M, et al. Aluminium-induced, reversible microcytic anemia in chronic renal failure: clinical and experimental studies. Clin Nephrol 1983;19:285.
37. Schroeder TM, Caspers ML. Kinetics of aluminium induced inhibition of delta-aminolevulinic acid dehydratase in vitro. Biochem Pharmacol 1996;52:927-31.
38. Caramelo CA, Cannata JB, Rodeles MR, Fernandez JL, Mosquera JR, Monzu B, Outeirino J, Blum J, Andrea C, Lopez FA, et al. Mechanism of aluminum induced microcytosis: lesson from accidental aluminum intoxication. Kidney Int 1995;47:164-8.
39. Danks DM. Copper deficiency in humans. Ann Rev Nutr 1988;8:235.
40. Williams DM. Copper deficiency in humans. Semin Hematol 1983;20:118.
41. Castillo Duran C, Uauy R. Copper deficiency impairs growth of infants recovering from malnutrition. Am J Clin Nutr 1988; 47:710.
42. Levy Y, Zeharia A, et al. Copper deficiency in infants fed cow milk. J Pediatr 1985; 106:786.
43. Menkes JH, Alter M, et al. A sex-linked recessive disorders with ritardation of growth, peculiar hair and focal cerebral and cerebellar degeneration. Pediatrics 1962; 29:764.
44. Vulpe C, Levinson B, et al. Isolation of a candidate gene for Menkes disease and evidence that it encodes a copper transporting ATPase. Nat Genet 1993;3:7.
45. Bull PC, Thomas GR, et al. The Wilson’s disease gene is a putative copper transporting P-type ATPase similar to the Menkes gene. Nat Genet 1993;5:327.
46. Yoshida K, Furiatha K, Takeda S, et al. A mutation in the ceruloplasmin gene is associated with systemic hemosiderosis in humans. Nat Genet 1995;9:267-72.
47. Harris ZL, Takahashi Y, Miyajima H, Serizawa M, MacGillivray RTA, Gitlin JD. Aceruloplasminemia: a molecular of this disordes of iron metabolism. Proc Natl Acad Sci USA 1995;92:2539-43.
48. Sergio Piomelli. Lead poisoning. In: Nathan DG, Orkin SH (eds). Hematology of infancy and childhood, 5a ed., Philadelphia: W.B. Saunders Co, 1998:480.
49. Shigern Sassa, Atallah Kappas. The porphyrias. In: Nathan DG, Orkin SH (eds). Philadelphia: Hematology of infancy and childhood, 5a ed., WB Saunders Co, 1998: 463.