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The most important differential is whether the patient has ACD alone or ACD with ongoing [[iron deficiency anemia]] (ACD/IDA). The following parameters will distinguish the two:  
The most important differential is whether the patient has ACD alone or ACD with ongoing [[iron deficiency anemia]] (ACD/IDA). The following parameters will distinguish the two:  


●Soluble [[transferrin receptor]] levels (sTfR) and/or the sTfR-[[ferritin]] index sTfR and the sTfR-[[ferritin]] index are normal in uncomplicated ACD, while both are elevated when IDA is also present<ref name="pmid25044010">{{cite journal |vauthors=Archer NM, Shmukler BE, Andolfo I, Vandorpe DH, Gnanasambandam R, Higgins JM, Rivera A, Fleming MD, Sachs F, Gottlieb PA, Iolascon A, Brugnara C, Alper SL, Nathan DG |title=Hereditary xerocytosis revisited |journal=Am. J. Hematol. |volume=89 |issue=12 |pages=1142–6 |date=December 2014 |pmid=25044010 |pmc=4237618 |doi=10.1002/ajh.23799 |url=}}</ref>.
●Soluble [[transferrin receptor]] levels (sTfR) and/or the sTfR-[[ferritin]] index sTfR and the sTfR-[[ferritin]] index are normal in uncomplicated ACD, while both are elevated when IDA is also present<ref name="pmid25044010">{{cite journal |vauthors=Archer NM, Shmukler BE, Andolfo I, Vandorpe DH, Gnanasambandam R, Higgins JM, Rivera A, Fleming MD, Sachs F, Gottlieb PA, Iolascon A, Brugnara C, Alper SL, Nathan DG |title=Hereditary xerocytosis revisited |journal=Am. J. Hematol. |volume=89 |issue=12 |pages=1142–6 |date=December 2014 |pmid=25044010 |pmc=4237618 |doi=10.1002/ajh.23799 |url=}}</ref>


●Percentage of [[hypochromic]] [[red cells]] and [[reticulocyte]] [[hemoglobin]] may help<ref name="pmid14500582">{{cite journal |vauthors=Brugnara C |title=Iron deficiency and erythropoiesis: new diagnostic approaches |journal=Clin. Chem. |volume=49 |issue=10 |pages=1573–8 |date=October 2003 |pmid=14500582 |doi= |url=}}</ref><ref name="pmid12089176">{{cite journal |vauthors=Thomas C, Thomas L |title=Biochemical markers and hematologic indices in the diagnosis of functional iron deficiency |journal=Clin. Chem. |volume=48 |issue=7 |pages=1066–76 |date=July 2002 |pmid=12089176 |doi= |url=}}</ref>.
●Percentage of [[hypochromic]] [[red cells]] and [[reticulocyte]] [[hemoglobin]] may help<ref name="pmid14500582">{{cite journal |vauthors=Brugnara C |title=Iron deficiency and erythropoiesis: new diagnostic approaches |journal=Clin. Chem. |volume=49 |issue=10 |pages=1573–8 |date=October 2003 |pmid=14500582 |doi= |url=}}</ref><ref name="pmid12089176">{{cite journal |vauthors=Thomas C, Thomas L |title=Biochemical markers and hematologic indices in the diagnosis of functional iron deficiency |journal=Clin. Chem. |volume=48 |issue=7 |pages=1066–76 |date=July 2002 |pmid=12089176 |doi= |url=}}</ref>


●[[Bone marrow]] examination in n difficult cases the diagnosis can often be established by bone marrow examination. Findings in the most common disorders include:
●[[Bone marrow]] examination in n difficult cases the diagnosis can often be established by bone marrow examination. Findings in the most common disorders include:
 
*ACD: Normal to increased [[iron]] in [[bone marrow]] [[macrophages]] while [[erythroid]] precursors may show decreased to absent [[iron]]
●ACD: Normal to increased [[iron]] in [[bone marrow]] [[macrophages]] while [[erythroid]] precursors may show decreased to absent [[iron]]
*Iron deficiency: No stainable [[iron]] in [[macrophages]] and [[erythroid]] precursors
 
●Iron deficiency: No stainable [[iron]] in [[macrophages]] and [[erythroid]] precursors.


=== Myelodysplastic syndromes ===
=== Myelodysplastic syndromes ===
Line 29: Line 27:
●Serum [[erythropoietin]] (EPO) levels lower in ACD than in patients with IDA and comparable degrees of [[anemia]]<ref name="pmid16434484">{{cite journal |vauthors=Theurl I, Mattle V, Seifert M, Mariani M, Marth C, Weiss G |title=Dysregulated monocyte iron homeostasis and erythropoietin formation in patients with anemia of chronic disease |journal=Blood |volume=107 |issue=10 |pages=4142–8 |date=May 2006 |pmid=16434484 |doi=10.1182/blood-2005-08-3364 |url=}}</ref>.
●Serum [[erythropoietin]] (EPO) levels lower in ACD than in patients with IDA and comparable degrees of [[anemia]]<ref name="pmid16434484">{{cite journal |vauthors=Theurl I, Mattle V, Seifert M, Mariani M, Marth C, Weiss G |title=Dysregulated monocyte iron homeostasis and erythropoietin formation in patients with anemia of chronic disease |journal=Blood |volume=107 |issue=10 |pages=4142–8 |date=May 2006 |pmid=16434484 |doi=10.1182/blood-2005-08-3364 |url=}}</ref>.


●Oral [[iron]] supplementation for four to six weeks may help in the differentiation between ACD and ACD/IDA.
●Oral [[iron]] supplementation for four to six weeks may help in the differentiation between ACD and ACD/IDA


=== Endocrine disorders ===
=== Endocrine disorders ===
Line 35: Line 33:


=== Miscellaneous ===
=== Miscellaneous ===
IDA, [[thalassemia]], sideroblastic anemias, and the [[Sideroblastic anemia|sideroblastic]] variants of the [[myelodysplastic syndrome]]<ref name="pmid25271605">{{cite journal |vauthors=DeLoughery TG |title=Microcytic anemia |journal=N. Engl. J. Med. |volume=371 |issue=14 |pages=1324–31 |date=October 2014 |pmid=25271605 |doi=10.1056/NEJMra1215361 |url=}}</ref>.
IDA, [[thalassemia]], sideroblastic anemias, and the [[Sideroblastic anemia|sideroblastic]] variants of the [[myelodysplastic syndrome]]<ref name="pmid25271605">{{cite journal |vauthors=DeLoughery TG |title=Microcytic anemia |journal=N. Engl. J. Med. |volume=371 |issue=14 |pages=1324–31 |date=October 2014 |pmid=25271605 |doi=10.1056/NEJMra1215361 |url=}}</ref>


Anemia must be differentiated based on different laboratory findings including [[mean cell volume]] ([[MCV]]), reticulocytosis, and hemolysis.
Anemia must be differentiated based on different laboratory findings including [[mean cell volume]] ([[MCV]]), reticulocytosis, and hemolysis.
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! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Specific finding on blood smear
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Specific finding on blood smear
|}
|}


==References==
==References==

Revision as of 23:16, 29 November 2018

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Omer Kamal, M.D.[2]

Overview

The most important differential is whether the patient has ACD alone or ACD with ongoing iron deficiency anemia (ACD/IDA). The following parameters will distinguish the two: Soluble transferrin receptor levels (sTfR) and/or the sTfR-ferritin index sTfR and the sTfR-ferritin index are normal in uncomplicated ACD, while both are elevated when IDA is also. Percentage of hypochromic red cells and reticulocyte hemoglobin may help.

Differential Diagnosis

Concomitant iron deficiency

The most important differential is whether the patient has ACD alone or ACD with ongoing iron deficiency anemia (ACD/IDA). The following parameters will distinguish the two:

●Soluble transferrin receptor levels (sTfR) and/or the sTfR-ferritin index sTfR and the sTfR-ferritin index are normal in uncomplicated ACD, while both are elevated when IDA is also present[1]

●Percentage of hypochromic red cells and reticulocyte hemoglobin may help[2][3]

●Bone marrow examination in n difficult cases the diagnosis can often be established by bone marrow examination. Findings in the most common disorders include:

Myelodysplastic syndromes

Single or multi-lineage dysplastic changes with or without increased number of sideroblasts, including ring forms, are commonly seen in patients with myelodysplasia

Sideroblastic anemias

Presence of ring sideroblasts on bone marrow examination

●Serum erythropoietin (EPO) levels lower in ACD than in patients with IDA and comparable degrees of anemia[4].

●Oral iron supplementation for four to six weeks may help in the differentiation between ACD and ACD/IDA

Endocrine disorders

Hyperthyroidism, hypothyroidism, panhypopituitarism, and primary and secondary hyperparathyroidism may also present with a normocytic, normochromic hypoproliferative anemia.

Miscellaneous

IDA, thalassemia, sideroblastic anemias, and the sideroblastic variants of the myelodysplastic syndrome[5]

Anemia must be differentiated based on different laboratory findings including mean cell volume (MCV), reticulocytosis, and hemolysis.

To review the differential diagnosis of anemia, see below table.

To review the differential diagnosis of microcytic anemia, click here.

To review the differential diagnosis of normocytic anemia, click here.

To review the differential diagnosis of macrocytic anemia, click here.

To review the differential diagnosis of hypochromic anemia, click here.

To review the differential diagnosis of normochromic anemia, click here.

To review the differential diagnosis of anisochromic anemia, click here.

To review the differential diagnosis of hemolytic anemia, click here.

To review the differential diagnosis of anemia with intrinsic hemolysis, click here.

To review the differential diagnosis of anemia with extrinsic hemolysis, click here.

To review the differential diagnosis of anemia with low reticulocytosis, click here.

To review the differential diagnosis of anemia with normal reticulocytosis, click here.

To review the differential diagnosis of anemia with high reticulocytosis, click here.

Disease Genetics Clinical manifestation Lab findings
History Symptoms Signs Hemolysis Intrinsic/

Extrinsic

Hb concentration MCV RDW Reticulocytosis Haptoglobin levels Hepcidin Iron studies Specific finding on blood smear
Serum iron Serum Tfr level Transferrin or TIBC Ferritin Transferrin saturation
Iron deficiency anemia[6] − − − Hypochromic Microcytic ↑ Nl or ↓ Nl Nl ↓ ↑ ↑ ↓ ↓↓↓
Iron deficiency anemia (early phase)[7] − − − Normochromic Normocytic ↑ ↓ Nl Nl ↓ ↑ ↑ ↓ ↓
Lead poisoning[8] −
  • House painted with chipped paint
 − − Hypochromic Microcytic Nl Nl or ↓ Nl Nl Nl to ↓ Nl Nl Nl to ↓ −
  • RBCs retain aggregates of rRNA
  • Basophilic stippling
Sideroblastic anemia[9] − − Hypochromic Microcytic Nl Nl or ↓ Nl Nl ↑ Nl Nl to ↓ ↑ −
Disease Genetics History Symptoms Signs Hemolysis Intrinsic/

Extrinsic

Hb concentration MCV RDW Reticulocytosis Haptoglobin levels Hepcidin Serum iron Serum Tfr level IBC Ferritin Transferrin saturation Specific finding on blood smear
Anemia of chronic disease[10] − − − − Hypochromic Microcytic Nl Nl or ↓ Nl ↑ ↓ Nl ↓ ↑ − NA
Thalassemia[11] α-thalassemia
  • α- globin gene deletions
  • Cis deletions
  • Trans deletions

β-thalassemia

α-thalassemia

β-thalassemia

− − Hypochromic Microcytic Nl
  • Thalassemia trait: Nl or ↓
  • Thalassemia Syndromes: ↑
 Nl Nl Nl to ↑ Nl Nl ↑ Nl to ↑
G6pd deficiency[12]
  • History of using
 + Intrinsic Normochromic Normocytic ↑ ↑ but usually causes resolution within 4-7 days ↓ ↓ Nl to ↑ Nl ↑ ↑ ↑
Pyruvate kinase deficiency[13] + Intrinsic Normochromic Normocytic ↑ ↑ ↓ Nl ↑ Nl Nl ↑ −
Disease Genetics History Symptoms Signs Hemolysis Intrinsic/

Extrinsic

Hb concentration MCV RDW Reticulocytosis Haptoglobin levels Hepcidin Serum iron Serum Tfr level IBC Ferritin Transferrin saturation Specific finding on blood smear
Sickle cell anemia[14] + Intrinsic Normochromic Normocytic ↑ ↑ ↓ Nl or moderately ↑ Nl Nl Nl or moderately ↑ ↓ Nl
HbC disease[15]
  • Glutamic acid–to-lysine mutation in β-globin
 + Intrinsic Normochromic Normocytic ↑ ↑ ↓ Nl Nl Nl Nl ↓ −
Paroxysmal nocturnal hemoglobinuria[16][17] + Intrinsic Normochromic Normocytic ↑ ↑ ↓ Nl ↓ Nl ↑ ↓ − NA
Hereditary spherocytosis[18] + Intrinsic Normochromic Normocytic ↑ ↑ ↓ Nl ↓ Nl ↑ Nl −
  • Small, round RBCs with less surface area and no central pallor
Disease Genetics History Symptoms Signs Hemolysis Intrinsic/

Extrinsic

Hb concentration MCV RDW Reticulocytosis Haptoglobin levels Hepcidin Serum iron Serum Tfr level IBC Ferritin Transferrin saturation Specific finding on blood smear
Microangiopathic hemolytic anemia[19][20] − Associated with + Extrinsic Normochromic Normocytic ↑ ↑ ↓ Nl ↓ Nl − ↑ −
  • Helmet cells
Macroangiopathic hemolytic anemia[21] Associated with + Extrinsic Normochromic Normocytic ↑ ↑ ↓ Nl ↓ Nl − − −
Autoimmune hemolytic anemia[22] − Associated with:
  • Painful, blue fingers and toes with cold weather
 + Extrinsic Normochromic Normocytic ↑ ↑ ↓ Nl ↓ Nl − − −
  • RBC agglutination
Aplastic anemia[23]
  • Symptoms based on underlying condition
 − − Normochromic Normocytic ↑ ↓ Nl Nl ↓ ↓ Nl ↑ ↓
Disease Genetics History Symptoms Signs Hemolysis Intrinsic/

Extrinsic

Hb concentration MCV RDW Reticulocytosis Haptoglobin levels Hepcidin Serum iron Serum Tfr level IBC Ferritin Transferrin saturation Specific finding on blood smear
Folate deficiency[24]
  • Impaired DNA synthesis
 − − Anisochromic Macrocytic ↑ ↓ Nl Nl ↑ ↑ ↓ ↑ ↑
Vitamin B12 deficiency[25] − − Anisochromic Macrocytic ↑ ↓ Nl Nl ↑ ↑ ↓ ↑ ↑
Orotic aciduria[26]
  • Neurological manifestation
 − − Anisochromic Macrocytic ↑ ↓ Nl Nl ↑ ↑ ↓ ↑ ↑ NA
Fanconi anemia[27]
  • Significant for bilateral short thumbs
 − − Anisochromic Macrocytic ↑ ↓ Nl Nl ↑ ↑ ↓ ↑ ↑
Disease Genetics History Symptoms Signs Hemolysis Intrinsic/

Extrinsic

Hb concentration MCV RDW Reticulocytosis Haptoglobin levels Hepcidin Serum iron Serum Tfr level IBC Ferritin Transferrin saturation Specific finding on blood smear
Diamond-Blackfan anemia[28] Mutations in:
  • RPL5
  • RPL11
  • RPL35A
  • RPS7
  • RPS10
  • RPS17
  • RPS19
  • RPS24
  • RPS26
 − − Anisochromic Macrocytic Nl ↓ Nl Nl ↑ ↑ ↓ ↑ ↑ NA
Infections[29] − Associated with + Extrinsic Normochromic Normocytic ↑ ↑ ↓ Nl Nl Nl − − −
Chronic kidney disease[30] − − − Normochromic Normocytic ↑ Nl/↑ Nl ↑ ↓ − ↓ ↑ ↓ Nl
Liver disease[31] −
  • Hepatitis
  • Binge drinking
  • Gall bladder disease
 − − Anisochromic Macrocytic ↑ ↑ Nl Nl ↑ ↑ ↓ ↑ ↑
Alcoholism[32] − − − Anisochromic Macrocytic ↑ ↑ Nl Nl ↑ ↑ ↓ ↑ ↑
Disease Genetics History Symptoms Signs Hemolysis Intrinsic/

Extrinsic

Hb concentration MCV RDW Reticulocytosis Haptoglobin levels Hepcidin Serum iron Serum Tfr level IBC Ferritin Transferrin saturation Specific finding on blood smear

References

  1. ↑ Archer NM, Shmukler BE, Andolfo I, Vandorpe DH, Gnanasambandam R, Higgins JM, Rivera A, Fleming MD, Sachs F, Gottlieb PA, Iolascon A, Brugnara C, Alper SL, Nathan DG (December 2014). "Hereditary xerocytosis revisited". Am. J. Hematol. 89 (12): 1142–6. doi:10.1002/ajh.23799. PMC 4237618. PMID 25044010.
  2. ↑ Brugnara C (October 2003). "Iron deficiency and erythropoiesis: new diagnostic approaches". Clin. Chem. 49 (10): 1573–8. PMID 14500582.
  3. ↑ Thomas C, Thomas L (July 2002). "Biochemical markers and hematologic indices in the diagnosis of functional iron deficiency". Clin. Chem. 48 (7): 1066–76. PMID 12089176.
  4. ↑ Theurl I, Mattle V, Seifert M, Mariani M, Marth C, Weiss G (May 2006). "Dysregulated monocyte iron homeostasis and erythropoietin formation in patients with anemia of chronic disease". Blood. 107 (10): 4142–8. doi:10.1182/blood-2005-08-3364. PMID 16434484.
  5. ↑ DeLoughery TG (October 2014). "Microcytic anemia". N. Engl. J. Med. 371 (14): 1324–31. doi:10.1056/NEJMra1215361. PMID 25271605.
  6. ↑ Camaschella C (May 2015). "Iron-deficiency anemia". N. Engl. J. Med. 372 (19): 1832–43. doi:10.1056/NEJMra1401038. PMID 25946282.
  7. ↑ De Andrade Cairo RC, Rodrigues Silva L, Carneiro Bustani N, Ferreira Marques CD (June 2014). "Iron deficiency anemia in adolescents; a literature review". Nutr Hosp. 29 (6): 1240–9. doi:10.3305/nh.2014.29.6.7245. PMID 24972460.
  8. ↑ Bain BJ (December 2014). "Lead poisoning". Am. J. Hematol. 89 (12): 1141. doi:10.1002/ajh.23852. PMID 25220013.
  9. ↑ Bottomley SS, Fleming MD (August 2014). "Sideroblastic anemia: diagnosis and management". Hematol. Oncol. Clin. North Am. 28 (4): 653–70, v. doi:10.1016/j.hoc.2014.04.008. PMID 25064706.
  10. ↑ Roy CN (2010). "Anemia of inflammation". Hematology Am Soc Hematol Educ Program. 2010: 276–80. doi:10.1182/asheducation-2010.1.276. PMID 21239806.
  11. ↑ Zainal NZ, Alauddin H, Ahmad S, Hussin NH (December 2014). "α-Thalassemia with Haemoglobin Adana mutation: prenatal diagnosis". Malays J Pathol. 36 (3): 207–11. PMID 25500521.
  12. ↑ Luzzatto L, Seneca E (February 2014). "G6PD deficiency: a classic example of pharmacogenetics with on-going clinical implications". Br. J. Haematol. 164 (4): 469–80. doi:10.1111/bjh.12665. PMC 4153881. PMID 24372186.
  13. ↑ Grace RF, Zanella A, Neufeld EJ, Morton DH, Eber S, Yaish H, Glader B (September 2015). "Erythrocyte pyruvate kinase deficiency: 2015 status report". Am. J. Hematol. 90 (9): 825–30. doi:10.1002/ajh.24088. PMC 5053227. PMID 26087744.
  14. ↑ Singh PC, Ballas SK (March 2015). "Emerging drugs for sickle cell anemia". Expert Opin Emerg Drugs. 20 (1): 47–61. doi:10.1517/14728214.2015.985587. PMID 25431087.
  15. ↑ Lemonne N, Billaud M, Waltz X, Romana M, Hierso R, Etienne-Julan M, Connes P (2016). "Rheology of red blood cells in patients with HbC disease". Clin. Hemorheol. Microcirc. 61 (4): 571–7. doi:10.3233/CH-141906. PMID 25335812.
  16. ↑ Bunyaratvej A, Butthep P (January 1992). "Cytometric analysis of paroxysmal nocturnal hemoglobinuria erythrocytes". J Med Assoc Thai. 75 Suppl 1: 237–42. PMID 1402472.
  17. ↑ Kahng J, Kim Y, Kim JO, Koh K, Lee JW, Han K (January 2015). "A novel marker for screening paroxysmal nocturnal hemoglobinuria using routine complete blood count and cell population data". Ann Lab Med. 35 (1): 35–40. doi:10.3343/alm.2015.35.1.35. PMC 4272963. PMID 25553278.
  18. ↑ Da Costa L, Galimand J, Fenneteau O, Mohandas N (July 2013). "Hereditary spherocytosis, elliptocytosis, and other red cell membrane disorders". Blood Rev. 27 (4): 167–78. doi:10.1016/j.blre.2013.04.003. PMID 23664421.
  19. ↑ Morishita E (July 2015). "[Diagnosis and treatment of microangiopathic hemolytic anemia]". Rinsho Ketsueki (in Japanese). 56 (7): 795–806. doi:10.11406/rinketsu.56.795. PMID 26251142.
  20. ↑ George JN, Charania RS (March 2013). "Evaluation of patients with microangiopathic hemolytic anemia and thrombocytopenia". Semin. Thromb. Hemost. 39 (2): 153–60. doi:10.1055/s-0032-1333538. PMID 23390027.
  21. ↑ Westphal RG, Azen EA (May 1971). "Macroangiopathic hemolytic anemia due to congenital cardiovascular anomalies". JAMA. 216 (9): 1477–8. PMID 5108522.
  22. ↑ Hill QA (October 2015). "Autoimmune hemolytic anemia". Hematology. 20 (9): 553–4. doi:10.1179/1024533215Z.000000000401. PMID 26447931.
  23. ↑ Dolberg OJ, Levy Y (2014). "Idiopathic aplastic anemia: diagnosis and classification". Autoimmun Rev. 13 (4–5): 569–73. doi:10.1016/j.autrev.2014.01.014. PMID 24424170.
  24. ↑ Koike H, Takahashi M, Ohyama K, Hashimoto R, Kawagashira Y, Iijima M, Katsuno M, Doi H, Tanaka F, Sobue G (March 2015). "Clinicopathologic features of folate-deficiency neuropathy". Neurology. 84 (10): 1026–33. doi:10.1212/WNL.0000000000001343. PMID 25663227.
  25. ↑ Hunt A, Harrington D, Robinson S (September 2014). "Vitamin B12 deficiency". BMJ. 349: g5226. PMID 25189324.
  26. ↑ Grohmann K, Lauffer H, Lauenstein P, Hoffmann GF, Seidlitz G (April 2015). "Hereditary orotic aciduria with epilepsy and without megaloblastic anemia". Neuropediatrics. 46 (2): 123–5. doi:10.1055/s-0035-1547341. PMID 25757096.
  27. ↑ Alter BP (2014). "Fanconi anemia and the development of leukemia". Best Pract Res Clin Haematol. 27 (3–4): 214–21. doi:10.1016/j.beha.2014.10.002. PMC 4254647. PMID 25455269.
  28. ↑ Vlachos A, Blanc L, Lipton JM (June 2014). "Diamond Blackfan anemia: a model for the translational approach to understanding human disease". Expert Rev Hematol. 7 (3): 359–72. doi:10.1586/17474086.2014.897923. PMID 24665981.
  29. ↑ Bustinduy AL, Parraga IM, Thomas CL, Mungai PL, Mutuku F, Muchiri EM, Kitron U, King CH (March 2013). "Impact of polyparasitic infections on anemia and undernutrition among Kenyan children living in a Schistosoma haematobium-endemic area". Am. J. Trop. Med. Hyg. 88 (3): 433–40. doi:10.4269/ajtmh.12-0552. PMC 3592521. PMID 23324217.
  30. ↑ Drawz P, Rahman M (June 2015). "Chronic kidney disease". Ann. Intern. Med. 162 (11): ITC1–16. doi:10.7326/AITC201506020. PMID 26030647.
  31. ↑ Marks PW (July 2013). "Hematologic manifestations of liver disease". Semin. Hematol. 50 (3): 216–21. doi:10.1053/j.seminhematol.2013.06.003. PMID 23953338.
  32. ↑ Yokoyama A, Yokoyama T, Brooks PJ, Mizukami T, Matsui T, Kimura M, Matsushita S, Higuchi S, Maruyama K (May 2014). "Macrocytosis, macrocytic anemia, and genetic polymorphisms of alcohol dehydrogenase-1B and aldehyde dehydrogenase-2 in Japanese alcoholic men". Alcohol. Clin. Exp. Res. 38 (5): 1237–46. doi:10.1111/acer.12372. PMID 24588059.


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