Macrocytic anemia differential diagnosis: Difference between revisions

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{{Macrocytic anemia}}
__NOTOC__
{{CMG}}
[[Image:Home_logo1.png|right|250px|link=https://www.wikidoc.org/index.php/Macrocytic_anemia]]
{{CMG}}; {{AE}} {{ADS}}
==Overview==
==Overview==
'''Macrocytosis''' is the enlargement of [[red blood cell]]s with near-constant [[haemoglobin]] concentration, and is defined by a [[mean corpuscular volume]] (MCV) of greater than 100 femtolitres (the precise criterion varies between laboratories).
Megaloblastic anemia needs to be diffrentiated from other causes of anemia.
 
==Differentiating Macrocytic Anemia from Other Diseases==
 
'''''To review the differential diagnosis of anemia, click [[Anemia#Differentiating Anemia from Other Diseases|here]].''''' 
 
{|
! rowspan="3" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Disease
! rowspan="3" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Genetics
! colspan="5" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Clinical manifestation
! colspan="12" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Lab findings
|-
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |History
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Symptoms
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Signs
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Hemolysis
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Intrinsic/Extrinsic
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Hb concentration
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |MCV
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |RDW
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Reticulocytosis
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Haptoglobin levels
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Hepcidin
! colspan="5" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Iron studies
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Specific finding on blood smear
|-
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Serum iron
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Serum Tfr level
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Transferrin or TIBC
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Ferritin
! style="background: #4479BA; color: #FFFFFF; text-align: center;" | Transferrin saturation
|-
! align="center" style="background:#DCDCDC;" |[[Folate deficiency]]<ref name="pmid25663227">{{cite journal |vauthors=Koike H, Takahashi M, Ohyama K, Hashimoto R, Kawagashira Y, Iijima M, Katsuno M, Doi H, Tanaka F, Sobue G |title=Clinicopathologic features of folate-deficiency neuropathy |journal=Neurology |volume=84 |issue=10 |pages=1026–33 |date=March 2015 |pmid=25663227 |doi=10.1212/WNL.0000000000001343 |url=}}</ref>
| align="left" style="background:#F5F5F5;" |
* Impaired [[DNA]] synthesis
| align="left" style="background:#F5F5F5;" |
* [[Long-term effects of alcohol|Alcohol consumption]]
* History of using drugs like [[methotrexate]], [[trimethoprim]], and [[phenytoin]]
* Low socioeconomic groups with poor nutrition
* Older people
* [[Pregnancy|Pregnant]] and [[lactating]] women
| align="left" style="background:#F5F5F5;" |
* No neurological symptoms vs [[Vitamin B12 deficiency|B12 deficiency]]
* [[Odinophagia|Odynophagia]]
* [[Stomatitis|Angular stomatitis]]
| align="left" style="background:#F5F5F5;" |
* [[Glossitis]]
* Signs of [[Congestive heart failure|heart failure]]
* [[Anencephaly]] and [[spina bifida]]
| align="center" style="background:#F5F5F5;" |−
| align="center" style="background:#F5F5F5;" |−
| align="center" style="background:#F5F5F5;" |Anisochromic
| align="center" style="background:#F5F5F5;" |[[Macrocytic anemia|Macrocytic]]
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |↑
| align="left" style="background:#F5F5F5;" |
* [[Macrocytosis|RBC macrocytosis]]
* [[Neutrophil|Hypersegmented neutrophils]]
* [[Pancytopenia]] in severe cases
*
|-
! align="center" style="background:#DCDCDC;" |[[Vitamin B12 deficiency]]<ref name="pmid25189324">{{cite journal |vauthors=Hunt A, Harrington D, Robinson S |title=Vitamin B12 deficiency |journal=BMJ |volume=349 |issue= |pages=g5226 |date=September 2014 |pmid=25189324 |doi= |url=}}</ref>
| align="left" style="background:#F5F5F5;" |
* Impaired [[DNA synthesis]]
| align="left" style="background:#F5F5F5;" |
* [[Pernicious anemia]]
* [[Crohn's disease]]
* [[Gastrectomy]]
* [[Vegan|Veganism]]
* [[Diphyllobothrium|Diphyllobothrium latum]] infection
| align="left" style="background:#F5F5F5;" |
* [[Psychosis]]
* [[Insomnia]]
* [[Depression]]
* Cognitive slowing
* [[Restless leg syndrome]]
| align="left" style="background:#F5F5F5;" |
* Neurological deficit
* [[Myelopathy]]
* [[Memory loss]] with reduced attention span
* [[Nystagmus]]
* Positive [[Romberg test|romberg sign]]
* Positive [[Lhermitte's sign]]
| align="center" style="background:#F5F5F5;" |−
| align="center" style="background:#F5F5F5;" |−
| align="center" style="background:#F5F5F5;" |Anisochromic
| align="center" style="background:#F5F5F5;" |[[Macrocytic anemia|Macrocytic]]
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |↑
| align="left" style="background:#F5F5F5;" |
* [[Senile]] [[neutrophil]]
* [[Anisocytosis]]
* [[Ovalocytosis|Ovalocytes]]
|-
! align="center" style="background:#DCDCDC;" |[[Orotic aciduria]]<ref name="pmid25757096">{{cite journal |vauthors=Grohmann K, Lauffer H, Lauenstein P, Hoffmann GF, Seidlitz G |title=Hereditary orotic aciduria with epilepsy and without megaloblastic anemia |journal=Neuropediatrics |volume=46 |issue=2 |pages=123–5 |date=April 2015 |pmid=25757096 |doi=10.1055/s-0035-1547341 |url=}}</ref>
| align="left" style="background:#F5F5F5;" |
* [[Autosomal recessive]]
* Deficiency of enzyme [[Uridine monophosphate synthetase|UMPS]]
| align="left" style="background:#F5F5F5;" |
* Episodic [[Nausea and vomiting|vomiting]]
* [[Rhabdomyolysis]]
| align="left" style="background:#F5F5F5;" |
* [[Coma]]
* [[Gastrointestinal tract|Gastrointestinal]] manifestation
| align="left" style="background:#F5F5F5;" |
* Neurological manifestation
| align="center" style="background:#F5F5F5;" |−
| align="center" style="background:#F5F5F5;" |−
| align="center" style="background:#F5F5F5;" |Anisochromic
| align="center" style="background:#F5F5F5;" |[[Macrocytic anemia|Macrocytic]]
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |NA
|-
! align="center" style="background:#DCDCDC;" |[[Fanconi anemia]]<ref name="pmid25455269">{{cite journal |vauthors=Alter BP |title=Fanconi anemia and the development of leukemia |journal=Best Pract Res Clin Haematol |volume=27 |issue=3-4 |pages=214–21 |date=2014 |pmid=25455269 |pmc=4254647 |doi=10.1016/j.beha.2014.10.002 |url=}}</ref>
| align="left" style="background:#F5F5F5;" |
* [[Autosomal recessive]]
* [[X-linked recessive]]
| align="left" style="background:#F5F5F5;" |
* History of [[anemia]] at age 16
| align="left" style="background:#F5F5F5;" |
* [[Hypopigmentation]]
* [[Café au lait spot|Cafe-au-lait patches]]
* Radial ray anomaly
| align="left" style="background:#F5F5F5;" |
* Significant for bilateral short thumbs
| align="center" style="background:#F5F5F5;" |−
| align="center" style="background:#F5F5F5;" |−
| align="center" style="background:#F5F5F5;" |Anisochromic
| align="center" style="background:#F5F5F5;" |[[Macrocytic anemia|Macrocytic]]
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |↑
| align="left" style="background:#F5F5F5;" |
* Nl appearing [[White blood cells|WBC]], [[Red blood cell|RBC]] and [[Platelet|Platelets]]
* But the number is greatly reduced
|-
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Disease
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Genetics
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |History
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Symptoms
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Signs
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Hemolysis
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Intrinsic/Extrinsic
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Hb concentration
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |MCV
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |RDW
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Reticulocytosis
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Haptoglobin levels
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Hepcidin
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Serum iron
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Serum Tfr level
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |IBC
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Ferritin
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Transferrin saturation
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Specific finding on blood smear
|-
! align="center" style="background:#DCDCDC;" |[[Diamond-Blackfan anemia]]<ref name="pmid24665981">{{cite journal |vauthors=Vlachos A, Blanc L, Lipton JM |title=Diamond Blackfan anemia: a model for the translational approach to understanding human disease |journal=Expert Rev Hematol |volume=7 |issue=3 |pages=359–72 |date=June 2014 |pmid=24665981 |doi=10.1586/17474086.2014.897923 |url=}}</ref>
| align="left" style="background:#F5F5F5;" |Mutations in:
* ''RPL5''
* ''RPL11''
* ''RPL35A''
* ''RPS7''
* ''RPS10''
* ''RPS17''
* ''RPS19''
* ''RPS24''
* ''RPS26''
| align="left" style="background:#F5F5F5;" |
* Associated with [[myelodysplastic syndrome]]
* Increased risk of [[AML]]
| align="left" style="background:#F5F5F5;" |
* [[Pale skin]]
* Sleepiness
* [[Murmur|Heart murmurs]]
| align="left" style="background:#F5F5F5;" |
* Triphalangeal  thumbs
* [[Short stature]]
* [[Microcephaly]]
* [[Hypertelorism]]
* [[Ptosis]]
* [[Micrognathia]]
| align="center" style="background:#F5F5F5;" |−
| align="center" style="background:#F5F5F5;" |−
| align="center" style="background:#F5F5F5;" |Anisochromic
| align="center" style="background:#F5F5F5;" |[[Macrocytic anemia|Macrocytic]]
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |NA
|-
! align="center" style="background:#DCDCDC;" |[[Hepato-biliary diseases|Liver disease]]<ref name="pmid23953338">{{cite journal |vauthors=Marks PW |title=Hematologic manifestations of liver disease |journal=Semin. Hematol. |volume=50 |issue=3 |pages=216–21 |date=July 2013 |pmid=23953338 |doi=10.1053/j.seminhematol.2013.06.003 |url=}}</ref>
| align="center" style="background:#F5F5F5;" |−
| align="left" style="background:#F5F5F5;" |
* [[Hepatitis]]
* Binge drinking
* Gall bladder disease
| align="left" style="background:#F5F5F5;" |
* [[Jaundice]]
* [[Abdominal pain]]
* [[Itchy skin]]
| align="left" style="background:#F5F5F5;" |
* [[Ascites]]
* Right upper quadrant pain
* [[Hepatomegaly]]
* [[Edema|Swelling]] in the legs
* [[Ankle swelling]]
| align="center" style="background:#F5F5F5;" |−
| align="center" style="background:#F5F5F5;" |−
| align="center" style="background:#F5F5F5;" |Anisochromic
| align="center" style="background:#F5F5F5;" |[[Macrocytic anemia|Macrocytic]]
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |↑
| align="left" style="background:#F5F5F5;" |
* [[Macrocyte|Round macrocytes]]
* [[Macrocyte|Target macrocytes]]
|-
! align="center" style="background:#DCDCDC;" |[[Alcoholism]]<ref name="pmid24588059">{{cite journal |vauthors=Yokoyama A, Yokoyama T, Brooks PJ, Mizukami T, Matsui T, Kimura M, Matsushita S, Higuchi S, Maruyama K |title=Macrocytosis, macrocytic anemia, and genetic polymorphisms of alcohol dehydrogenase-1B and aldehyde dehydrogenase-2 in Japanese alcoholic men |journal=Alcohol. Clin. Exp. Res. |volume=38 |issue=5 |pages=1237–46 |date=May 2014 |pmid=24588059 |doi=10.1111/acer.12372 |url=}}</ref>
| align="center" style="background:#F5F5F5;" |−
| align="left" style="background:#F5F5F5;" |
* History of increased [[Effects of alcohol on the body|alcohol intake]]
* [[Folic acid deficiency]]
| align="left" style="background:#F5F5F5;" |
* [[Memory impairment]]
* [[Nausea]]
* [[Sweating]]
| align="left" style="background:#F5F5F5;" |
* Truncal [[obesity]]
* [[Asterixis]]
* [[Encephalopathy]]
* [[Spider angiomas]]
* [[Hematemesis]]
* [[Gynecomastia]]
| align="center" style="background:#F5F5F5;" |−
| align="center" style="background:#F5F5F5;" |−
| align="center" style="background:#F5F5F5;" |Anisochromic
| align="center" style="background:#F5F5F5;" |[[Macrocytic anemia|Macrocytic]]
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |↑
| align="left" style="background:#F5F5F5;" |
* [[Macrocyte|Oval macrocytes]]
* [[Neutrophil|Hypersegmented neutrophils]]
|-
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Disease
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Genetics
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |History
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Symptoms
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Signs
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Hemolysis
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Intrinsic/Extrinsic
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Hb concentration
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |MCV
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |RDW
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Reticulocytosis
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Haptoglobin levels
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Hepcidin
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Serum iron
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Serum Tfr level
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |IBC
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Ferritin
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Transferrin saturation
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Specific finding on blood smear
|}
 
==References==
==References==
{{Reflist|2}}
{{Reflist|2}}
[[es:Anemia megaloblástica]]
[[gl:Anemia megaloblástica]]
[[he:אנמיה מגלובלסטית]]
[[it:Anemia megaloblastica]]
[[pl:Niedokrwistość megaloblastyczna]]
[[pt:Anemia megaloblástica]]
[[ru:Пернициозная анемия]]
[[sl:Megaloblastna anemija]]
[[sr:Мегалобластна анемија]]
[[tr:Megaloblastik anemi]]
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[[Category:Disease]]
[[Category:Blood disorders]]
[[Category:Hematology]]

Latest revision as of 20:56, 26 February 2019

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

Overview

Megaloblastic anemia needs to be diffrentiated from other causes of anemia.

Differentiating Macrocytic Anemia from Other Diseases

To review the differential diagnosis of anemia, 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
Folate deficiency[1]
  • Impaired DNA synthesis
Anisochromic Macrocytic Nl Nl
Vitamin B12 deficiency[2] Anisochromic Macrocytic Nl Nl
Orotic aciduria[3]
  • Neurological manifestation
Anisochromic Macrocytic Nl Nl NA
Fanconi anemia[4]
  • 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[5] Mutations in:
  • RPL5
  • RPL11
  • RPL35A
  • RPS7
  • RPS10
  • RPS17
  • RPS19
  • RPS24
  • RPS26
Anisochromic Macrocytic Nl Nl Nl NA
Liver disease[6]
  • Hepatitis
  • Binge drinking
  • Gall bladder disease
Anisochromic Macrocytic Nl Nl
Alcoholism[7] 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. 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.
  2. Hunt A, Harrington D, Robinson S (September 2014). "Vitamin B12 deficiency". BMJ. 349: g5226. PMID 25189324.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.