Anemia: Difference between revisions

Jump to navigation Jump to search
No edit summary
m (Bot: Removing from Primary care)
(32 intermediate revisions by 10 users not shown)
Line 1: Line 1:
__NOTOC__
{| class="infobox" style="float:right;"
|-
| [[File:Siren.gif|30px|link=Anemia resident survival guide]]|| <br> || <br>
| [[Anemia resident survival guide|'''Resident'''<br>'''Survival'''<br>'''Guide''']]
|}
{{Anemia}}
'''For patient information click [[Anemia (patient information)|here]]'''
'''For patient information click [[Anemia (patient information)|here]]'''


{{Infobox_Disease
{{CMG}} {{shyam}} {{AE}}{{SSW}}, {{VKG}}, {{MJ}}
| Name          = Anemia
 
| Image          =
 
| Caption        =  
{{SK}} Anaemia; low hemoglobin; low hemoglobin levels (peripheral blood)
| DiseasesDB    = 663
 
| ICD10          = {{ICD10|D|50||d|50}}-{{ICD10|D|64||d|60}}
==Overview==
| ICD9          = {{ICD9|280}}-{{ICD9|285}}
Anemia is the most common disorder of the blood. Anemia, from the Greek (Ἀναιμία) (an-haîma) meaning "without blood", is a deficiency of [[Red blood cell|red blood cells]] (RBCs) and/or [[hemoglobin]]. This results in a reduced ability of blood to transfer [[oxygen]] to the [[Tissue (biology)|tissues]], causing tissue [[Hypoxia (medical)|hypoxia]]. Since all human cells depend on [[oxygen]] for survival, varying degrees of anemia can have a wide range of clinical consequences. [[Hemoglobin]] (the oxygen-carrying [[protein]] in the red blood cells) must be present to ensure adequate [[oxygenation]] of all tissues and organs.
| ICDO          =
 
| OMIM          =  
The three main classes of anemia include excessive blood loss (acutely such as a [[hemorrhage]] or chronically through low-volume loss), excessive blood cell destruction ([[hemolysis]]), or deficient red blood cell production (ineffective [[hematopoiesis]]). There are multiple subtypes of anemia within those major categories. Anemia is defined as a [[hemoglobin]] concentration (Hb) of less than 12 g/dL in women and less than 13 g/dL in men, or alternatively, [[hematocrit]] of less than 36% in women and less than 40% in men.
| MedlinePlus    = 000560
 
| MeshID        = D000740
==Classification==
}}
Here is a simplified schematic of this approach:{{familytree/start}}
{{Anemia}}
{{familytree | | | | | | | | | A01 | | | | | | |A01=Anemia}}
{{CMG}}
{{familytree | | | | | | |,|-|-|^|-|-|.| | | | |}}
{{familytree | | | | | | C01 | | | | C02 | | | |C01=[[Reticulocyte production index]] shows inadequate production response to anemia.|C02=[[Reticulocyte production index]] shows appropriate response to anemia = '''ongoing''' hemolysis or blood loss without RBC production problem.}}
{{familytree | | |,|-|-|-|+|-|-|-|.| | | | | |}}
{{familytree | | E01 | | E02 | | E03 | |E01=No clinical findings consistent with hemolysis or blood loss: pure disorder of production.|E02=Clinical findings '''and''' abnormal MCV: hemolysis or loss '''and''' chronic disorder of production*.|E03=Clinical findings '''and''' normal MCV= '''acute''' hemolysis or loss without adequate time for [[bone marrow]] production to compensate**.}}
{{familytree | |,|+|-|-|+|-|-|-|-|.| | | | | |}}
{{familytree | F01 | | F02 | | | F03 | | | | |F01=[[Macrocytic anemia]] (MCV>100)|F02=[[Normocytic anemia]] (80<MCV<100)|F03=[[Microcytic anemia]] (MCV<80)}}
{{familytree/end}}''*'' ''For instance, sickle cell anemia with superimposed iron deficiency; chronic gastric bleeding with B12 and folate deficiency; and other instances of anemia with more than one cause.'' ''**'' ''Confirm by repeating reticulocyte count: ongoing combination of low reticulocyte production index, normal MCV and hemolysis or loss may be seen in bone marrow failure or anemia of chronic disease, with superimposed or related hemolysis or blood loss.''
===Classification Based on Red blood Cell Size===
Here is a schematic representation of how to consider anemia with [[Mean corpuscular volume|MCV]] as the starting point:{{familytree/start}}
{{familytree | | | | | | | | | | | | A01 | | | | | | | | |A01=Anemia}}
{{familytree | | | | |,|-|-|-|-|-|-|-|+|-|-|-|-|-|-|-|.| |}}
{{familytree | | | | B01 | | | | | | B02 | | | | | | B03 |B01=[[Macrocytic anemia]] (MCV>100)|B02=[[Normocytic anemia]] (80<MCV<100)|B03=[[Microcytic anemia]] (MCV<80)}}
{{familytree | | | | | | | | |,|-|-|-|^|-|-|-|.| | | | | |}}
{{familytree | | | | | | | | C01 | | | | | | C02 | | | | |C01=High [[reticulocyte]] count|C02=Low [[reticulocyte]] count}}
{{familytree/end}}Other characteristics visible on the peripheral smear may provide valuable clues about a more specific diagnosis; for example, abnormal [[white blood cell]]s may point to a cause in the [[bone marrow]].
====Microcytic Anemia====
Microcytic anemia is primarily a result of [[hemoglobin]] synthesis failure/insufficiency, which could be caused by several etiologies:
*[[Heme]] synthesis defect
**[[Iron deficiency anemia|Iron deficiency]]
**[[Anemia of chronic disease|Anemia of Chronic Disorders]] (more commonly presenting as normocytic anemia)
*[[Globular protein|Globin]] synthesis defect
**Alpha- and beta-thalassemia
**HbE syndrome
**HbC syndrome
**Various other unstable [[hemoglobin]] diseases
*[[Sideroblastic anemia|Sideroblastic]] defect
**Hereditary [[sideroblastic anemia]]
**Acquired [[sideroblastic anemia]] including [[lead]] toxicity
**Reversible [[sideroblastic anemia]]
 
*[[Iron deficiency anemia]] is the most common type of anemia overall and it has many causes. RBCs often appear [[hypochromic]] (paler than usual) and microcytic (smaller than usual) when viewed with a microscope.
*[[hemoglobinopathy|Hemoglobinopathies]] are much rarer (apart from communities where these conditions are prevalent) such as Southeast Asia.
====Normocytic Anemia====
Normocytic anaemia occurs when the overall Hb levels are decreased, but the red blood cell size ([[MCV]]) remains normal. Causes include:
*Acute [[hemorrhage|blood loss]]
*[[Anemia of chronic disease]]
*[[Aplastic anemia]] (bone marrow failure)
*[[Hemolytic anemia]]
*[[Erythropoietin deficiency]]
*Renal failure
*Early phase of acute blood loss
====Macrocytic Anemia====
*Megaloblastic anemia is the most common cause of macrocytic anemia.
*[[Megaloblastic anemia]] is due to a deficiency of either [[vitamin B12]], [[folic acid]] (or both), or to autoimmune processes that cause deficiency in either, such as [[pernicious anemia]]. Liver disease and hypothyroidism can also contribute to megaloblastic anemia. Deficiency in folate and/or Vitamin B12 can be due either to inadequate intake or [[malabsorption|insufficient absorption]]. Folate deficiency normally does not produce neurological symptoms, while B12 deficiency does.
*[[Alcoholism]] causes a [[macrocytosis]], although not specifically anemia.
*[[Methotrexate]], [[zidovudine]], and other drugs that inhibit [[DNA replication]]. This is the most common etiology in nonalcoholic patients.
===Specific Anemias===
*[[Anemia of prematurity]] occurs in premature infants at 2 to 6 weeks of age and results from diminished [[erythropoietin]] response to declining [[hematocrit]] levels.
*[[Fanconi anemia]] is an hereditary disorder or defect featuring [[aplastic anemia]] and various other abnormalities.
*[[Hemolytic anemia]] causes a separate constellation of symptoms (also featuring [[jaundice]] and elevated [[lactate dehydrogenase|LDH]] levels) with numerous potential causes. It can be [[autoimmune]], [[immune]],  [[genetic disorder|hereditary]] or mechanical (e.g. [[heart surgery]]). It can result (because of cell fragmentation) in a [[microcytic anemia]], a normochromic anemia, or (because of premature release of immature red blood cells from the bone marrow), a macrocytic anemia.
*[[Hereditary spherocytosis]] is a hereditary defect that results in defects in the RBC cell membrane, causing the erythrocytes to be sequestered and destroyed by the spleen.  This leads to a decrease in the number of circulating RBCs and, hence, anemia.
*[[sickle-cell disease|Sickle-cell anemia]], a hereditary disorder, is due to [[Zygosity|homozygous]] hemoglobin S genes.
*[[Warm autoimmune hemolytic anemia]] is an anemia caused by autoimmune attack against red blood cells, primarily by IgG. This is responsive to corticosteroid therapy.
*[[Cold agglutinin hemolytic anemia]] is primarily mediated by IgM. This is not responsive to corticosteroid therapy but is responsive to rituximab.
*[[Pernicious anemia]] is a form of [[megaloblastic anaemia]] due to [[vitamin B12]] deficiency dependent on impaired absorption of vitamin B12. It is due to loss of intrinsic factor in the gastrointestinal tract.
*[[Myelophthisic anemia]] or [[Myelophthisis]] is a severe type of anemia resulting from the replacement of bone marrow by other materials, such as malignant tumors or granulomas.
 
==Differentiating Anemia from Other Diseases==
 
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 [[Microcytic anemia#Differentiating Microcytic Anemia from Other Diseases|here]].'''''


==[[Anemia overview|Overview]]==
'''''To review the differential diagnosis of normocytic anemia, click [[Normocytic anemia#Differentiating Normocytic Anemia from Other Diseases|here]].'''''


==[[Anemia historical perspective|Historical Perspective]]==
'''''To review the differential diagnosis of macrocytic anemia, click [[Macrocytic anemia differential diagnosis|here]].'''''


==[[Anemia classification|Classification]]==
'''''To review the differential diagnosis of hypochromic anemia, click [[Hypochromic anemia#Differentiating Hypochromic Anemia from Other Diseases|here]].'''''


==[[Anemia pathophysiology|Pathophysiology]]==
'''''To review the differential diagnosis of normochromic anemia, click [[Normochromic anemia#Differentiating Normochromic Anemia from Other Diseases|here]].'''''


==[[Anemia causes|Causes]]==
'''''To review the differential diagnosis of anisochromic anemia, click [[Anisochromic anemia#Differentiating Anisochromic Anemia from Other Diseases|here]].'''''


==[[Anemia differential diagnosis|Differentiating Anemia from Other Diseases]]==
'''''To review the differential diagnosis of hemolytic anemia, click [[Hemolytic anemia differential diagnosis|here]].'''''


==[[Anemia epidemiology and demographics|Epidemiology and Demographics]]==
'''''To review the differential diagnosis of anemia with intrinsic hemolysis, click [[Anemia with intrinsic hemolysis#Differentiating Anemia with intrinsic hemolysis from Other Diseases|here]].'''''


==[[Anemia risk factors|Risk Factors]]==
'''''To review the differential diagnosis of anemia with extrinsic hemolysis, click [[Anemia with extrinsic hemolysis#Differentiating Anemia with extrinsic hemolysis from Other Diseases|here]].'''''


==[[Anemia screening|Screening]]==
'''''To review the differential diagnosis of anemia with low reticulocytosis, click [[Anemia with low reticulocytosis#Differentiating Anemia with low reticulocytosis from Other Diseases|here]].'''''


==[[Anemia natural history, complications and prognosis|Natural History, Complications and Prognosis]]==
'''''To review the differential diagnosis of anemia with normal reticulocytosis, click [[Anemia with normal reticulocytosis#Differentiating Anemia with normal reticulocytosis from Other Diseases|here]].'''''


==Diagnosis==
'''''To review the differential diagnosis of anemia with high reticulocytosis, click [[Anemia with high reticulocytosis#Differentiating Anemia with high reticulocytosis 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;" |[[Iron deficiency anemia]]<ref name="pmid25946282">{{cite journal |vauthors=Camaschella C |title=Iron-deficiency anemia |journal=N. Engl. J. Med. |volume=372 |issue=19 |pages=1832–43 |date=May 2015 |pmid=25946282 |doi=10.1056/NEJMra1401038 |url=}}</ref>
| align="center" style="background:#F5F5F5;" | −
| align="left" style="background:#F5F5F5;" |
* [[Menorrhagia]]
* [[GI]] loss
* [[Gastrointestinal tract|GI]] surgery
* [[Pregnancy]]
| align="left" style="background:#F5F5F5;" |
* [[Koilonychia]]
* [[Pica]]
| align="left" style="background:#F5F5F5;" |
* [[Glossitis]]
* [[Cheilosis]]
* [[Dysphagia]]
| align="center" style="background:#F5F5F5;" | −
| align="center" style="background:#F5F5F5;" | −
| align="center" style="background:#F5F5F5;" | [[Hypochromic anemia|Hypochromic]]
| align="center" style="background:#F5F5F5;" | [[Microcytic anemia|Microcytic]]
| align="center" style="background:#F5F5F5;" | ↑
| align="center" style="background:#F5F5F5;" | Nl or ↓
| 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;" |
* Central [[pallor]]
|-
! align="center" style="background:#DCDCDC;" |[[Iron deficiency anemia]] (early phase)<ref name="pmid24972460">{{cite journal |vauthors=De Andrade Cairo RC, Rodrigues Silva L, Carneiro Bustani N, Ferreira Marques CD |title=Iron deficiency anemia in adolescents; a literature review |journal=Nutr Hosp |volume=29 |issue=6 |pages=1240–9 |date=June 2014 |pmid=24972460 |doi=10.3305/nh.2014.29.6.7245 |url=}}</ref>
| align="center" style="background:#F5F5F5;" | −
| align="left" style="background:#F5F5F5;" |
* [[Pica]]
* [[Glossitis]]
* [[Angular cheilitis|Cheilosis]]
| align="left" style="background:#F5F5F5;" |
* [[Fatigue]]
* [[Headache]]
| align="left" style="background:#F5F5F5;" |
* [[Koilonychia]]
* Conjunctival [[pallor]]
* [[Xeroderma|Dry skin]]
| align="center" style="background:#F5F5F5;" | −
| align="center" style="background:#F5F5F5;" | −
| align="center" style="background:#F5F5F5;" | [[Normochromic anemia|Normochromic]]
| align="center" style="background:#F5F5F5;" | [[Normocytic anemia|Normocytic]]
| 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;" |
* Pencil [[Cell (biology)|cells]]
* [[Hereditary elliptocytosis|Elliptocytosis]]
* Hypochromasia
|-
! align="center" style="background:#DCDCDC;" |[[Lead poisoning]]<ref name="pmid25220013">{{cite journal |vauthors=Bain BJ |title=Lead poisoning |journal=Am. J. Hematol. |volume=89 |issue=12 |pages=1141 |date=December 2014 |pmid=25220013 |doi=10.1002/ajh.23852 |url=}}</ref>
| align="center" style="background:#F5F5F5;" | −
| align="left" style="background:#F5F5F5;" |
* House painted with chipped paint
| align="left" style="background:#F5F5F5;" |
* Burtonian lines
* [[Basophilic]] [[Stippling (dentistry)|stippling]]
* [[Wrist drop]]
* [[Foot drop]]
| align="left" style="background:#F5F5F5;" |
* [[Wrist drop]]
* [[Foot drop]]
* Burtonian lines
| align="center" style="background:#F5F5F5;" | −
| align="center" style="background:#F5F5F5;" | −
| align="center" style="background:#F5F5F5;" | [[Intravascular|Hypochromic]]
| align="center" style="background:#F5F5F5;" | [[Microcytic anemia|Microcytic]]
| align="center" style="background:#F5F5F5;" | Nl
| align="center" style="background:#F5F5F5;" | Nl or ↓
| align="center" style="background:#F5F5F5;" | Nl
| align="center" style="background:#F5F5F5;" | Nl
| align="center" style="background:#F5F5F5;" | Nl to ↓
| align="center" style="background:#F5F5F5;" | Nl
| align="center" style="background:#F5F5F5;" | Nl
| align="center" style="background:#F5F5F5;" | Nl to ↓
| align="center" style="background:#F5F5F5;" | −
| align="left" style="background:#F5F5F5;" |
* [[Red blood cell|RBCs]] retain aggregates of [[Ribosomal RNA|rRNA]]
* Basophilic stippling
|-
! align="center" style="background:#DCDCDC;" |[[Sideroblastic anemia]]<ref name="pmid25064706">{{cite journal |vauthors=Bottomley SS, Fleming MD |title=Sideroblastic anemia: diagnosis and management |journal=Hematol. Oncol. Clin. North Am. |volume=28 |issue=4 |pages=653–70, v |date=August 2014 |pmid=25064706 |doi=10.1016/j.hoc.2014.04.008 |url=}}</ref>
| align="left" style="background:#F5F5F5;" |
* Defect in [[ALA synthase]] gene
* [[Autosomal dominant]]
* [[Autosomal recessive]]
* [[X-linked]]
| align="left" style="background:#F5F5F5;" |
* [[Alcohol]] abuse
* [[Isoniazid]] use
* [[Chloramphenicol]] use
* Lead poisoning
* [[Idiopathic]]
| align="left" style="background:#F5F5F5;" |
* [[Seborrheic dermatitis]]
* Glossy Tongue
* [[Tingling]]
| align="left" style="background:#F5F5F5;" |
* Patient present with symptoms of [[Vitamin B6]], [[copper deficiency]] symptoms
| align="center" style="background:#F5F5F5;" | −
| align="center" style="background:#F5F5F5;" | −
| align="center" style="background:#F5F5F5;" | [[Hypochromic anemia|Hypochromic]]
| align="center" style="background:#F5F5F5;" | [[Microcytic anemia|Microcytic]]
| align="center" style="background:#F5F5F5;" | Nl
| align="center" style="background:#F5F5F5;" | Nl or ↓
| align="center" style="background:#F5F5F5;" | Nl
| align="center" style="background:#F5F5F5;" | Nl
| align="center" style="background:#F5F5F5;" | ↑
| align="center" style="background:#F5F5F5;" | Nl
| align="center" style="background:#F5F5F5;" | Nl to ↓
| align="center" style="background:#F5F5F5;" | ↑
| align="center" style="background:#F5F5F5;" | −
| align="left" style="background:#F5F5F5;" |
* Ringed [[Sideroblastic|sideroblasts]]
|-
! 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;" |[[Anemia of chronic disease]]<ref name="pmid21239806">{{cite journal |vauthors=Roy CN |title=Anemia of inflammation |journal=Hematology Am Soc Hematol Educ Program |volume=2010 |issue= |pages=276–80 |date=2010 |pmid=21239806 |doi=10.1182/asheducation-2010.1.276 |url=}}</ref>
| align="center" style="background:#F5F5F5;" | −
| align="left" style="background:#F5F5F5;" |
* [[Rheumatoid arthritis]]
* [[SLE]]
* [[Neoplasm]]
* [[Chronic kidney disease]]
| align="left" style="background:#F5F5F5;" |
* [[Headache]]
* [[Shortness of breath]]
| align="center" style="background:#F5F5F5;" | −
| align="center" style="background:#F5F5F5;" | −
| align="center" style="background:#F5F5F5;" | −
| align="center" style="background:#F5F5F5;" | [[Hypochromic anemia|Hypochromic]]
| align="center" style="background:#F5F5F5;" | [[Microcytic anemia|Microcytic]]
| align="center" style="background:#F5F5F5;" | Nl
| align="center" style="background:#F5F5F5;" | Nl or ↓
| align="center" style="background:#F5F5F5;" | Nl
| align="center" style="background:#F5F5F5;" | ↑
| align="center" style="background:#F5F5F5;" | ↓
| 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;" | NA
|-
! align="center" style="background:#DCDCDC;" |[[Thalassemia]]<ref name="pmid25500521">{{cite journal |vauthors=Zainal NZ, Alauddin H, Ahmad S, Hussin NH |title=α-Thalassemia with Haemoglobin Adana mutation: prenatal diagnosis |journal=Malays J Pathol |volume=36 |issue=3 |pages=207–11 |date=December 2014 |pmid=25500521 |doi= |url=}}</ref>
| align="left" style="background:#F5F5F5;" | '''[[Thalassemia|α-thalassemia]]'''
* '''''α'''''- globin gene deletions
* [[Cis]] deletions
* [[Trans]] deletions
'''[[Thalassemia|β-thalassemia]]'''
* [[Point mutation]] in [[Splice site|splice sites]] and promoter sequences
| align="left" style="background:#F5F5F5;" |
* Associated with [[parvovirus B19]]
| align="left" style="background:#F5F5F5;" | [[Thalassemia|'''α-thalassemia''']]
* [[Hydrops fetalis]]
[[Thalassemia|'''β-thalassemia''']]
* [[Skeletal]] deformities
* Chipmunk facies
| align="left" style="background:#F5F5F5;" |
* [[Hepatomegaly]]
* [[Splenomegaly]]
| align="center" style="background:#F5F5F5;" | −
| align="center" style="background:#F5F5F5;" | −
| align="center" style="background:#F5F5F5;" | [[Hypochromic anemia|Hypochromic]]
| align="center" style="background:#F5F5F5;" | [[Microcytic anemia|Microcytic]]
| align="center" style="background:#F5F5F5;" | Nl
| align="left" style="background:#F5F5F5;" |
* Thalassemia trait: Nl or ↓
* Thalassemia Syndromes: ↑
| align="center" style="background:#F5F5F5;" | Nl
| align="center" style="background:#F5F5F5;" | Nl
| align="center" style="background:#F5F5F5;" | Nl to ↑
| align="center" style="background:#F5F5F5;" | Nl
| align="center" style="background:#F5F5F5;" | Nl
| align="center" style="background:#F5F5F5;" | ↑
| align="center" style="background:#F5F5F5;" | Nl to ↑
| align="left" style="background:#F5F5F5;" |
* [[Target cell|Target cells]]
* Anisopoikilocytosis
|-
! align="center" style="background:#DCDCDC;" |[[Glucose 6 phosphate dehydrogenase deficiency|G6PD deficiency]]<ref name="pmid24372186">{{cite journal |vauthors=Luzzatto L, Seneca E |title=G6PD deficiency: a classic example of pharmacogenetics with on-going clinical implications |journal=Br. J. Haematol. |volume=164 |issue=4 |pages=469–80 |date=February 2014 |pmid=24372186 |pmc=4153881 |doi=10.1111/bjh.12665 |url=}}</ref>
| align="left" style="background:#F5F5F5;" |
* Defect in [[Glucose-6-phosphate dehydrogenase|G6PD]] enzyme
* X-Linked [[recessive]]
| align="left" style="background:#F5F5F5;" |
* History of using


[[Anemia history and symptoms|History and Symptoms]] | [[Anemia physical examination|Physical Examination]] | [[Anemia laboratory findings|Laboratory Findings]] | [[Anemia electrocardiogram|EKG]] | [[Anemia chest x ray|Chest X ray]] | [[Anemia CT|CT]] | [[Anemia echocardiography or ultrasound|Echocardiography or Ultrasound]] | [[Anemia other imaging findings|Other Imaging Findings]] | [[Anemia other diagnostic studies|Other Diagnostic Studies]]
** [[Sulfonamide (medicine)|Sulfa drugs]]
** [[Antimalarial drug|Antimalarials]]
** [[Fava bean|Fava Beans]]
* [[Infection|Infections]]
| align="left" style="background:#F5F5F5;" |
* [[Back pain]]
* [[Hemoglobinuria]]
| align="left" style="background:#F5F5F5;" |
* [[Back pain]]
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" |Intrinsic
| align="center" style="background:#F5F5F5;" |[[Normochromic anemia|Normochromic]]
| align="center" style="background:#F5F5F5;" |[[Normocytic anemia|Normocytic]]
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |↑ but usually causes resolution within 4-7 days
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |Nl to ↑
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |↑
| align="left" style="background:#F5F5F5;" |
* [[Red blood cell|RBC]] with [[Heinz bodies]]
* Bite [[Cell (biology)|cells]]
* Blister [[Cell (biology)|cells]]
*
|-
! align="center" style="background:#DCDCDC;" |[[Pyruvate kinase deficiency]]<ref name="pmid26087744">{{cite journal |vauthors=Grace RF, Zanella A, Neufeld EJ, Morton DH, Eber S, Yaish H, Glader B |title=Erythrocyte pyruvate kinase deficiency: 2015 status report |journal=Am. J. Hematol. |volume=90 |issue=9 |pages=825–30 |date=September 2015 |pmid=26087744 |pmc=5053227 |doi=10.1002/ajh.24088 |url=}}</ref>
| align="left" style="background:#F5F5F5;" |
* [[Mutation]] in the ''[[PKLR]]'' and ''[[PKM2|PKM]]'' gene
* [[Autosomal recessive]]
| align="left" style="background:#F5F5F5;" |
* [[Gallstones]]
| align="left" style="background:#F5F5F5;" |
* [[Hydrops fetalis]]
* [[Neonatal hyperbilirubinemia]]
* [[Iron overload]]
* [[Perinatal]] complications
| align="left" style="background:#F5F5F5;" |
* Skin [[ulcers]]
* [[Splenomegaly]]
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" | Intrinsic
| align="center" style="background:#F5F5F5;" | [[Normochromic anemia|Normochromic]]
| align="center" style="background:#F5F5F5;" | [[Normocytic anemia|Normocytic]]
| align="center" style="background:#F5F5F5;" | ↑
| align="center" style="background:#F5F5F5;" | ↑
| align="center" style="background:#F5F5F5;" | ↓
| 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="left" style="background:#F5F5F5;" |
* Prickle [[cells]]
* Polychromatophilic [[erythrocytes]]
|-
! 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;" |[[Sickle-cell disease|Sickle cell anemia]]<ref name="pmid25431087">{{cite journal |vauthors=Singh PC, Ballas SK |title=Emerging drugs for sickle cell anemia |journal=Expert Opin Emerg Drugs |volume=20 |issue=1 |pages=47–61 |date=March 2015 |pmid=25431087 |doi=10.1517/14728214.2015.985587 |url=}}</ref>
| align="left" style="background:#F5F5F5;" |
* Hbs [[point mutation]] causes a single [[Amino acid|amino acid]] replacement in β chain
| align="left" style="background:#F5F5F5;" |
* [[High altitude]]
* Low [[Oxygen]]
* [[Acidosis]]
* African-American race
* [[Parvovirus B19]] infection
| align="left" style="background:#F5F5F5;" |
* Painful crisis
** [[Dactylitis]]
** [[Priapism]]
** [[Acute chest syndrome]]
** [[Avascular necrosis|Avascular Necrosis]]
** [[Stroke]]
* [[Autosplenectomy]]
* [[Salmonella|Salmonella osteomyelitis]]
| align="left" style="background:#F5F5F5;" |
* [[Dactylitis]]
* [[Priapism]]
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" | Intrinsic
| align="center" style="background:#F5F5F5;" | [[Normochromic anemia|Normochromic]]
| align="center" style="background:#F5F5F5;" | [[Normocytic anemia|Normocytic]]
| align="center" style="background:#F5F5F5;" | ↑
| align="center" style="background:#F5F5F5;" | ↑
| align="center" style="background:#F5F5F5;" | ↓
| align="center" style="background:#F5F5F5;" | Nl or moderately ↑
| align="center" style="background:#F5F5F5;" | Nl
| align="center" style="background:#F5F5F5;" | Nl
| align="center" style="background:#F5F5F5;" | Nl or moderately ↑
| align="center" style="background:#F5F5F5;" | ↓
| align="center" style="background:#F5F5F5;" | Nl
| align="left" style="background:#F5F5F5;" |
* Increased [[erythropoiesis]]
* [[Howell-Jolly bodies]]
* [[Anisocytosis]]
|-
! align="center" style="background:#DCDCDC;" |HbC disease<ref name="pmid25335812">{{cite journal |vauthors=Lemonne N, Billaud M, Waltz X, Romana M, Hierso R, Etienne-Julan M, Connes P |title=Rheology of red blood cells in patients with HbC disease |journal=Clin. Hemorheol. Microcirc. |volume=61 |issue=4 |pages=571–7 |date=2016 |pmid=25335812 |doi=10.3233/CH-141906 |url=}}</ref>
| align="left" style="background:#F5F5F5;" |
* Glutamic acid–to-lysine [[mutation]] in β-globin
| align="left" style="background:#F5F5F5;" |
* [[Gallstone]]
| align="left" style="background:#F5F5F5;" |
* [[Joint pains]]
* Increased risk of [[Infection|infections]]
| align="left" style="background:#F5F5F5;" |
* [[Splenomegaly]]
* [[Gallstone disease|Cholelithiasis]]
* [[Avascular necrosis|Avascular necrosis of the femoral head]]
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" | Intrinsic
| align="center" style="background:#F5F5F5;" | [[Normochromic anemia|Normochromic]]
| align="center" style="background:#F5F5F5;" | [[Normocytic anemia|Normocytic]]
| align="center" style="background:#F5F5F5;" | ↑
| 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;" | Nl
| align="center" style="background:#F5F5F5;" | Nl
| align="center" style="background:#F5F5F5;" | ↓
| align="center" style="background:#F5F5F5;" | −
| align="left" style="background:#F5F5F5;" |
* Hemoglobin crystals inside [[RBCs]]
* [[Target cell|Target cells]]
|-
! align="center" style="background:#DCDCDC;" |[[Paroxysmal nocturnal hemoglobinuria]]<ref name="pmid1402472">{{cite journal |vauthors=Bunyaratvej A, Butthep P |title=Cytometric analysis of paroxysmal nocturnal hemoglobinuria erythrocytes |journal=J Med Assoc Thai |volume=75 Suppl 1 |issue= |pages=237–42 |date=January 1992 |pmid=1402472 |doi= |url=}}</ref><ref name="pmid25553278">{{cite journal |vauthors=Kahng J, Kim Y, Kim JO, Koh K, Lee JW, Han K |title=A novel marker for screening paroxysmal nocturnal hemoglobinuria using routine complete blood count and cell population data |journal=Ann Lab Med |volume=35 |issue=1 |pages=35–40 |date=January 2015 |pmid=25553278 |pmc=4272963 |doi=10.3343/alm.2015.35.1.35 |url=}}</ref>
| align="left" style="background:#F5F5F5;" |
* [[PIGA]] gene mutations
* Impaired  synthesis of [[GPI anchor]] for [[decay-accelerating  factor]]
| align="left" style="background:#F5F5F5;" |
* Associated with [[aplastic anemia]]
* [[Thrombosis]]
| align="left" style="background:#F5F5F5;" |
* [[Fatigue]]
* [[Chest pain]]
* [[Dyspnea]] on exertion
* [[Headache]]
| align="left" style="background:#F5F5F5;" |
* [[Hemolysis|Chronic hemolysis]]
* [[Hepatomegaly]]
* [[Ascites]]
* [[Papilledema]]
* Skin nodules
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" | Intrinsic
| align="center" style="background:#F5F5F5;" | [[Normochromic anemia|Normochromic]]
| align="center" style="background:#F5F5F5;" | [[Normocytic anemia|Normocytic]]
| align="center" style="background:#F5F5F5;" | ↑
| align="center" style="background:#F5F5F5;" | ↑
| align="center" style="background:#F5F5F5;" | ↓
| align="center" style="background:#F5F5F5;" | Nl
| align="center" style="background:#F5F5F5;" | ↓
| 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;" | NA
|-
! align="center" style="background:#DCDCDC;" |[[Hereditary spherocytosis]]<ref name="pmid23664421">{{cite journal |vauthors=Da Costa L, Galimand J, Fenneteau O, Mohandas N |title=Hereditary spherocytosis, elliptocytosis, and other red cell membrane disorders |journal=Blood Rev. |volume=27 |issue=4 |pages=167–78 |date=July 2013 |pmid=23664421 |doi=10.1016/j.blre.2013.04.003 |url=}}</ref>
| align="left" style="background:#F5F5F5;" |
* [[Mutations]] in [[Ankyrin]], [[Band 3]], [[Protein 4.2]], and [[spectrin]]
| align="left" style="background:#F5F5F5;" |
* Associated with [[parvovirus B19]]
* [[Cholelithiasis]]
* Megaloblastic crisis
| align="left" style="background:#F5F5F5;" |
* [[Aplastic crisis]]
| align="left" style="background:#F5F5F5;" |
* [[Splenomegaly]]
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" | Intrinsic
| align="center" style="background:#F5F5F5;" | [[Normochromic anemia|Normochromic]]
| align="center" style="background:#F5F5F5;" | [[Normocytic anemia|Normocytic]]
| align="center" style="background:#F5F5F5;" | ↑
| align="center" style="background:#F5F5F5;" | ↑
| align="center" style="background:#F5F5F5;" | ↓
| align="center" style="background:#F5F5F5;" | Nl
| align="center" style="background:#F5F5F5;" | ↓
| align="center" style="background:#F5F5F5;" | Nl
| align="center" style="background:#F5F5F5;" | ↑
| align="center" style="background:#F5F5F5;" | Nl
| align="center" style="background:#F5F5F5;" | −
| align="left" style="background:#F5F5F5;" |
* Small, round [[Red blood cell|RBC]]s with less surface area and no central pallor
|-
! 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;" |[[Microangiopathic hemolytic anemia]]<ref name="pmid26251142">{{cite journal |vauthors=Morishita E |title=[Diagnosis and treatment of microangiopathic hemolytic anemia] |language=Japanese |journal=Rinsho Ketsueki |volume=56 |issue=7 |pages=795–806 |date=July 2015 |pmid=26251142 |doi=10.11406/rinketsu.56.795 |url=}}</ref><ref name="pmid23390027">{{cite journal |vauthors=George JN, Charania RS |title=Evaluation of patients with microangiopathic hemolytic anemia and thrombocytopenia |journal=Semin. Thromb. Hemost. |volume=39 |issue=2 |pages=153–60 |date=March 2013 |pmid=23390027 |doi=10.1055/s-0032-1333538 |url=}}</ref>
| align="center" style="background:#F5F5F5;" | −
| align="left" style="background:#F5F5F5;" | Associated with
* [[Disseminated intravascular coagulation|DIC]]
* [[TTP]]
* [[Hemolytic-uremic syndrome|HUS]]
* [[SLE]]
* [[HELLP syndrome]]
* [[Hypertensive crisis|Hypertensive emergency]]
| align="left" style="background:#F5F5F5;" |
* [[Purpura]]
* [[Confusion]]
* [[Aphasia]]
* [[Diplopia]]
| align="left" style="background:#F5F5F5;" |
* [[Paresthesia|Numbness]] of an arm or hand
* [[Jaundice]]
* [[Pallor|Pale conjunctiva]]
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" | Extrinsic
| align="center" style="background:#F5F5F5;" | [[Normochromic anemia|Normochromic]]
| align="center" style="background:#F5F5F5;" | [[Normocytic anemia|Normocytic]]
| align="center" style="background:#F5F5F5;" | ↑
| align="center" style="background:#F5F5F5;" | ↑
| align="center" style="background:#F5F5F5;" | ↓
| align="center" style="background:#F5F5F5;" | Nl
| align="center" style="background:#F5F5F5;" | ↓
| align="center" style="background:#F5F5F5;" | Nl
| align="center" style="background:#F5F5F5;" | −
| align="center" style="background:#F5F5F5;" | ↑
| align="center" style="background:#F5F5F5;" | −
| align="left" style="background:#F5F5F5;" |
* Helmet cells
|-
! align="center" style="background:#DCDCDC;" |Macroangiopathic hemolytic anemia<ref name="pmid5108522">{{cite journal |vauthors=Westphal RG, Azen EA |title=Macroangiopathic hemolytic anemia due to congenital cardiovascular anomalies |journal=JAMA |volume=216 |issue=9 |pages=1477–8 |date=May 1971 |pmid=5108522 |doi= |url=}}</ref>
| align="left" style="background:#F5F5F5;" |
* [[Autoimmunity|Autoimmune]]
| align="left" style="background:#F5F5F5;" | Associated with
* [[Artificial heart valve|Prosthetic heart valves]]
* [[Aortic stenosis]]
| align="left" style="background:#F5F5F5;" |
* [[Pallor]]
* [[Fatigue]]
| align="left" style="background:#F5F5F5;" |
* Signs of [[anemia]]
* Complications of [[hemolysis]]
* Decreased vascular volume
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" | Extrinsic
| align="center" style="background:#F5F5F5;" | [[Normochromic anemia|Normochromic]]
| align="center" style="background:#F5F5F5;" | [[Normocytic anemia|Normocytic]]
| align="center" style="background:#F5F5F5;" | ↑
| align="center" style="background:#F5F5F5;" | ↑
| align="center" style="background:#F5F5F5;" | ↓
| align="center" style="background:#F5F5F5;" | Nl
| align="center" style="background:#F5F5F5;" | ↓
| align="center" style="background:#F5F5F5;" | Nl
| align="center" style="background:#F5F5F5;" | −
| align="center" style="background:#F5F5F5;" | −
| align="center" style="background:#F5F5F5;" | −
| align="left" style="background:#F5F5F5;" |  
* [[Spherocytosis|Spherocytes]] or [[Red blood cell|schistocytes]]
|-
! align="center" style="background:#DCDCDC;" |[[Autoimmune  hemolytic anemia]]<ref name="pmid26447931">{{cite journal |vauthors=Hill QA |title=Autoimmune hemolytic anemia |journal=Hematology |volume=20 |issue=9 |pages=553–4 |date=October 2015 |pmid=26447931 |doi=10.1179/1024533215Z.000000000401 |url=}}</ref>
| align="center" style="background:#F5F5F5;" | −
| align="left" style="background:#F5F5F5;" | Associated with:
* [[SLE]]
* [[Chronic lymphocytic leukemia|CLL]]
* [[Mycoplasma pneumonia]]
| align="left" style="background:#F5F5F5;" |  
* Painful blue fingers and toes on exposure to cold temperature
* [[Chest pain]]
* [[Rigor|Chills]]
* [[Dizziness]]
* [[Tachycardia]]
* [[Headache]]
* [[Fatigue]]
| align="left" style="background:#F5F5F5;" |
* Painful, blue fingers and toes with cold weather
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" | Extrinsic
| align="center" style="background:#F5F5F5;" | [[Normochromic anemia|Normochromic]]
| align="center" style="background:#F5F5F5;" | [[Normocytic anemia|Normocytic]]
| align="center" style="background:#F5F5F5;" | ↑
| align="center" style="background:#F5F5F5;" | ↑
| align="center" style="background:#F5F5F5;" | ↓
| align="center" style="background:#F5F5F5;" | Nl
| align="center" style="background:#F5F5F5;" | ↓
| align="center" style="background:#F5F5F5;" | Nl
| align="center" style="background:#F5F5F5;" | −
| align="center" style="background:#F5F5F5;" | −
| align="center" style="background:#F5F5F5;" | −
| align="left" style="background:#F5F5F5;" |
* [[Red blood cell|RBC]] agglutination
|-
! align="center" style="background:#DCDCDC;" |[[Aplastic anemia]]<ref name="pmid24424170">{{cite journal |vauthors=Dolberg OJ, Levy Y |title=Idiopathic aplastic anemia: diagnosis and classification |journal=Autoimmun Rev |volume=13 |issue=4-5 |pages=569–73 |date=2014 |pmid=24424170 |doi=10.1016/j.autrev.2014.01.014 |url=}}</ref>
| align="left" style="background:#F5F5F5;" |
* Constitutive expression of Tbet
* [[Mutation|Mutations]] in the [[perforin]] gene
* Mutations in ''SAP'' gene
| align="left" style="background:#F5F5F5;" |
* Exposure to [[Radiation]]
* Drugs like [[Benzene]], [[chloramphenicol]], [[Alkylating agent|alkylating agents]]
* Viral infections like [[EBV]], [[HIV]], [[Hepatitis]]
* [[Fanconi anemia]]
* Idiopathic like [[Immune]] mediated, primary stem cell defect
| align="left" style="background:#F5F5F5;" |
* Symptoms based on underlying condition
| align="left" style="background:#F5F5F5;" |
* Short stature
* [[Cafe-au-lait spots]]
* Thumb defects
* [[Radius (bone)|Radial]] defects
| align="center" style="background:#F5F5F5;" | −
| align="center" style="background:#F5F5F5;" |−
| align="center" style="background:#F5F5F5;" |[[Normochromic anemia|Normochromic]]
| align="center" style="background:#F5F5F5;" |[[Normocytic anemia|Normocytic]]
| 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;" |Nl
| align="center" style="background:#F5F5F5;" |↑
| align="center" style="background:#F5F5F5;" |↓
| align="left" style="background:#F5F5F5;" |
* [[Pancytopenia]]
* Fatty [[Infiltration (medical)|infiltration]]
|-
! 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;" |[[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;" |[[Infection|Infections]]<ref name="pmid23324217">{{cite journal |vauthors=Bustinduy AL, Parraga IM, Thomas CL, Mungai PL, Mutuku F, Muchiri EM, Kitron U, King CH |title=Impact of polyparasitic infections on anemia and undernutrition among Kenyan children living in a Schistosoma haematobium-endemic area |journal=Am. J. Trop. Med. Hyg. |volume=88 |issue=3 |pages=433–40 |date=March 2013 |pmid=23324217 |pmc=3592521 |doi=10.4269/ajtmh.12-0552 |url=}}</ref>
| align="center" style="background:#F5F5F5;" | −
| align="left" style="background:#F5F5F5;" | Associated with
* [[Malaria]]
* [[Babesia]]
| align="left" style="background:#F5F5F5;" |
* [[Fever]]
| align="left" style="background:#F5F5F5;" |
* [[Fever]]
* Signs of [[shock]]
* [[Headache]]
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" | Extrinsic
| align="center" style="background:#F5F5F5;" | [[Normochromic anemia|Normochromic]]
| align="center" style="background:#F5F5F5;" | [[Normocytic anemia|Normocytic]]
| align="center" style="background:#F5F5F5;" | ↑
| 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;" | Nl
| align="center" style="background:#F5F5F5;" | −
| align="center" style="background:#F5F5F5;" | −
| align="center" style="background:#F5F5F5;" | −
| align="left" style="background:#F5F5F5;" |
* [[Trophozoite]]
* Maltese crosses
|-
! align="center" style="background:#DCDCDC;" |[[Chronic renal failure|Chronic kidney disease]]<ref name="pmid26030647">{{cite journal |vauthors=Drawz P, Rahman M |title=Chronic kidney disease |journal=Ann. Intern. Med. |volume=162 |issue=11 |pages=ITC1–16 |date=June 2015 |pmid=26030647 |doi=10.7326/AITC201506020 |url=}}</ref>
| align="center" style="background:#F5F5F5;" |−
| align="left" style="background:#F5F5F5;" |
* [[Pericarditis]]
* [[Encephalopathy]]
* [[Incontinence|Rectal incontinence]]
* Decreased [[libido]]
* [[Restless legs syndrome|Restless leg syndrome]]
| align="left" style="background:#F5F5F5;" |
* [[Polyuria]]
* [[Hematuria]]
* [[Edema]]
| align="left" style="background:#F5F5F5;" |
* [[Hypertension]]
| align="center" style="background:#F5F5F5;" | −
| align="center" style="background:#F5F5F5;" |−
| align="center" style="background:#F5F5F5;" |[[Normochromic anemia|Normochromic]]
| align="center" style="background:#F5F5F5;" |[[Normocytic anemia|Normocytic]]
| 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;" |↓
| align="center" style="background:#F5F5F5;" |Nl
|-
! 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
|}


==Treatment==
==Medical Therapy==
If hemodynamic compromise is present, then immediate intervention is required which includes:
* Administration of O2 as needed
* [[Iron]], [[folate]], [[vitamin B12]] supplements as necessary
* IV fluids for maintenance of [[blood pressure]]
* For hemoglobins <8 gm/dl, blood transfusions are indicated
* Establishment of two large-bore IVs for cases of ongoing acute blood loss


[[Anemia ute renal failure medical therapy|Medical Therapy]] | [[Anemia primary prevention|Primary Prevention]] | [[Anemia secondary prevention|Secondary Prevention]] | [[Anemia cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Anemia future or investigational therapies|Future or Investigational Therapies]]
There are many different treatments for anemia and the treatment depends on severity and the cause.


Iron deficiency from nutritional causes is rare in non-menstruating adults (men and post-menopausal women). The diagnosis of iron deficiency mandates a search for potential sources of loss such as gastrointestinal bleeding from [[ulcers]] or [[colon cancer]]. Mild to moderate iron deficiency anemia is treated by iron supplementation with [[Iron(II) sulfate|ferrous sulfate]] or ferrous gluconate.  [[Vitamin C]] may aid in the body's ability to absorb iron.


Vitamin supplements given orally ([[folic acid]]) or subcutaneously ([[Cyanocobalamin|vitamin B-12]]) will replace specific deficiencies.


==References==
In anemia of chronic disease, anemia associated with chemotherapy, or anemia associated with [[renal disease]], some clinicians prescribe [[recombinant protein|recombinant]] [[erythropoietin]], [[epoetin alfa]], to stimulate red cell production.
* Breymann, Christian.  "Iron Deficiency and Anemia in Pregnancy: Modern Aspects of Diagnosis and Therapy."  Blood Cells, Molecules, and Diseases.  Nov/Dec: 2002.
* Conrad, Marcel E.  "Iron Deficiency Anemia."  EMedicine.  [[8 December]] [[2004]]
* Raymond, Tina.  "Anemia: Diagnosis, Treatment and Prevention."  Midwifery Today.  [[31 May]] [[1999]].
* Scrimshaw, Nevin. Iron deficiency. Scientific American Oct 1991 pp 46-52
* Schier, Stanley L. Approach to the adult patient with anemia. [http://www.uptodate.com Up-to-Date] (subscription required), accessed in Jan 2006, last changed June 2005.
* [http://whqlibdoc.who.int/trs/WHO_TRS_405.pdf WHO Scientific Group on Nutritional Anaemias. "Nutritional anaemias : ''report of a WHO scientific group (meeting held in Geneva from 13 to 17 March 1967)''". World Health Organization. Geneva, 1968.]


==See also==
In severe cases of anemia, or with ongoing blood loss, a [[blood transfusion]] may be necessary. Transfusions can be complication by circulatory overload and iron overload so much be used with caution.
* [[Hematology]]
* [[Human iron metabolism]]
* [[Heme]]
* [[Hemoglobin]]


==References==
====Contraindicated medications====
{{reflist|2}}
{{MedCondContrAbs|MedCond = Severe anemia|Methotrexate|Nitroglycerin}}


[[ar:فقر دم]]
===Blood Transfusions===
[[bn:রক্তশূন্যতা]]
*Doctors attempt to avoid [[blood transfusion]] in general, since multiple lines of evidence point to increased adverse patient clinical outcomes with more intensive transfusion strategies.  The physiological principle that reduction of oxygen delivery associated with anemia leads to adverse clinical outcomes is balanced by the finding that transfusion does not necessarily mitigate these adverse clinical outcomes. 
[[bs:Anemija]]
*In severe, acute bleeding, transfusions of donated [[blood]] are often lifesaving.  Improvements in battlefield casualty survival is attributable, at least in part, to the recent improvements in blood banking and transfusion techniques.
[[bg:Анемия]]
*Transfusion of the stable but anemic hospitalized patient has been the subject of numerous clinical trials, and transfusion is emerging as a deleterious intervention.
[[ca:Anèmia]]
*Four randomized controlled clinical trials have been conducted to evaluate aggressive versus conservative transfusion strategies in critically ill patients.  All four of these studies failed to find a benefit with more aggressive transfusion strategies.  <ref name="pmid9971864">{{cite journal |author=Hébert PC, Wells G, Blajchman MA, ''et al'' |title=A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group |journal=N. Engl. J. Med. |volume=340 |issue=6 |pages=409–17 |year=1999 |pmid=9971864 |doi=}}</ref><ref name="pmid9293831">{{cite journal |author=Bush RL, Pevec WC, Holcroft JW |title=A prospective, randomized trial limiting perioperative red blood cell transfusions in vascular patients |journal=Am. J. Surg. |volume=174 |issue=2 |pages=143–8 |year=1997 |pmid=9293831 |doi=}}</ref><ref name="pmid10532600">{{cite journal |author=Bracey AW, Radovancevic R, Riggs SA, ''et al'' |title=Lowering the hemoglobin threshold for transfusion in coronary artery bypass procedures: effect on patient outcome |journal=Transfusion |volume=39 |issue=10 |pages=1070–7 |year=1999 |pmid=10532600 |doi=}}</ref><ref name="pmid16960287">{{cite journal |author=McIntyre LA, Fergusson DA, Hutchison JS, ''et al'' |title=Effect of a liberal versus restrictive transfusion strategy on mortality in patients with moderate to severe head injury |journal=Neurocritical care |volume=5 |issue=1 |pages=4–9 |year=2006 |pmid=16960287 |doi=}}</ref>
[[cs:Chudokrevnost]]
*In addition, at least two retrospective studies have shown increases in adverse clinical outcomes with more aggressive transfusion strategies.<ref name="pmid14707558">{{cite journal |author=Corwin HL, Gettinger A, Pearl RG, ''et al'' |title=The CRIT Study: Anemia and blood transfusion in the critically ill--current clinical practice in the United States |journal=Crit. Care Med. |volume=32 |issue=1 |pages=39–52 |year=2004 |pmid=14707558 |doi=10.1097/01.CCM.0000104112.34142.79}}</ref><ref name="pmid12243637">{{cite journal |author=Vincent JL, Baron JF, Reinhart K, ''et al'' |title=Anemia and blood transfusion in critically ill patients |journal=JAMA |volume=288 |issue=12 |pages=1499–507 |year=2002 |pmid=12243637 |doi=}}</ref>
[[da:Anæmi]]
*On the whole, these studies suggest that aggressive transfusions, at least for hospitalized patients, may at best not improve any clinical parameter, and at worst lead to adverse outcomes.
[[de:Anämie]]
*A recent report suggests that the culprit is the depletion of [[nitric oxide]], an important [[vasodilator]], in banked blood.  The theory is that the transfusion of [[nitric oxide]]-depleted blood causes systemic [[vasoconstriction]], and exacerbates [[hypoxia (medical)|hypoxia]] in tissues at risk.<ref>MEDICAL SCIENCES
[[et:Aneemia]]
S-nitrosohemoglobin deficiency: A mechanism for loss of physiological activity in banked blood
[[es:Anemia]]
James D. Reynolds*, Gregory S. Ahearn{dagger}, Michael Angelo{dagger}, Jian Zhang{dagger}, Fred Cobb{dagger},{ddagger}, and Jonathan S. Stamler  Published online before print October 11, 2007
[[eo:Anemio]]
Proc. Natl. Acad. Sci. USA, 10.1073/pnas.0707958104  Accessed 10/15/07</ref>
[[eu:Anemia]]
[[fa:کم‌خونی]]
[[fr:Anémie]]
[[ko:빈혈]]
[[id:Anemia]]
[[ia:Anemia]]
[[it:Anemia]]
[[he:אנמיה]]
[[ku:Anemî]]
[[la:Anaemia]]
[[lt:Anemija]]
[[ms:Penyakit anemia]]
[[nl:Bloedarmoede]]
[[ja:貧血]]
[[no:Anemi]]
[[nn:Anemi]]
[[pl:Niedokrwistość]]
[[pt:Anemia]]
[[ro:Anemie]]
[[ru:Анемия]]
[[sq:Anemia]]
[[simple:Anemia]]
[[sk:Anémia]]
[[sr:Анемија]]
[[fi:Anemia]]
[[sv:Anemi]]
[[vi:Thiếu máu]]
[[tr:Kansızlık]]
[[uk:Анемія]]
[[bat-smg:Anemėjė]]
[[zh:贫血]]


{{WikiDoc Help Menu}}
==References==
{{WikiDoc Sources}}
{{Reflist|2}}


[[Category:Disease]]
[[Category:Disease]]

Revision as of 20:24, 29 July 2020



Resident
Survival
Guide

Anemia main page

Overview

Classification

Differential Diagnosis

Medical Therapy

For patient information click here

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Shyam Patel [2] Associate Editor(s)-in-Chief: Sargun Singh Walia M.B.B.S.[3], Vamsikrishna Gunnam M.B.B.S [4], Mehrian Jafarizade, M.D [5]


Synonyms and keywords: Anaemia; low hemoglobin; low hemoglobin levels (peripheral blood)

Overview

Anemia is the most common disorder of the blood. Anemia, from the Greek (Ἀναιμία) (an-haîma) meaning "without blood", is a deficiency of red blood cells (RBCs) and/or hemoglobin. This results in a reduced ability of blood to transfer oxygen to the tissues, causing tissue hypoxia. Since all human cells depend on oxygen for survival, varying degrees of anemia can have a wide range of clinical consequences. Hemoglobin (the oxygen-carrying protein in the red blood cells) must be present to ensure adequate oxygenation of all tissues and organs.

The three main classes of anemia include excessive blood loss (acutely such as a hemorrhage or chronically through low-volume loss), excessive blood cell destruction (hemolysis), or deficient red blood cell production (ineffective hematopoiesis). There are multiple subtypes of anemia within those major categories. Anemia is defined as a hemoglobin concentration (Hb) of less than 12 g/dL in women and less than 13 g/dL in men, or alternatively, hematocrit of less than 36% in women and less than 40% in men.

Classification

Here is a simplified schematic of this approach:

 
 
 
 
 
 
 
 
Anemia
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Reticulocyte production index shows inadequate production response to anemia.
 
 
 
Reticulocyte production index shows appropriate response to anemia = ongoing hemolysis or blood loss without RBC production problem.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No clinical findings consistent with hemolysis or blood loss: pure disorder of production.
 
Clinical findings and abnormal MCV: hemolysis or loss and chronic disorder of production*.
 
Clinical findings and normal MCV= acute hemolysis or loss without adequate time for bone marrow production to compensate**.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Macrocytic anemia (MCV>100)
 
Normocytic anemia (80<MCV<100)
 
 
Microcytic anemia (MCV<80)
 
 
 
 

* For instance, sickle cell anemia with superimposed iron deficiency; chronic gastric bleeding with B12 and folate deficiency; and other instances of anemia with more than one cause. ** Confirm by repeating reticulocyte count: ongoing combination of low reticulocyte production index, normal MCV and hemolysis or loss may be seen in bone marrow failure or anemia of chronic disease, with superimposed or related hemolysis or blood loss.

Classification Based on Red blood Cell Size

Here is a schematic representation of how to consider anemia with MCV as the starting point:

 
 
 
 
 
 
 
 
 
 
 
Anemia
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Macrocytic anemia (MCV>100)
 
 
 
 
 
Normocytic anemia (80<MCV<100)
 
 
 
 
 
Microcytic anemia (MCV<80)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
High reticulocyte count
 
 
 
 
 
Low reticulocyte count
 
 
 
 

Other characteristics visible on the peripheral smear may provide valuable clues about a more specific diagnosis; for example, abnormal white blood cells may point to a cause in the bone marrow.

Microcytic Anemia

Microcytic anemia is primarily a result of hemoglobin synthesis failure/insufficiency, which could be caused by several etiologies:

  • Iron deficiency anemia is the most common type of anemia overall and it has many causes. RBCs often appear hypochromic (paler than usual) and microcytic (smaller than usual) when viewed with a microscope.
  • Hemoglobinopathies are much rarer (apart from communities where these conditions are prevalent) such as Southeast Asia.

Normocytic Anemia

Normocytic anaemia occurs when the overall Hb levels are decreased, but the red blood cell size (MCV) remains normal. Causes include:

Macrocytic Anemia

  • Megaloblastic anemia is the most common cause of macrocytic anemia.
  • Megaloblastic anemia is due to a deficiency of either vitamin B12, folic acid (or both), or to autoimmune processes that cause deficiency in either, such as pernicious anemia. Liver disease and hypothyroidism can also contribute to megaloblastic anemia. Deficiency in folate and/or Vitamin B12 can be due either to inadequate intake or insufficient absorption. Folate deficiency normally does not produce neurological symptoms, while B12 deficiency does.
  • Alcoholism causes a macrocytosis, although not specifically anemia.
  • Methotrexate, zidovudine, and other drugs that inhibit DNA replication. This is the most common etiology in nonalcoholic patients.

Specific Anemias

Differentiating Anemia from Other Diseases

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[1] Hypochromic Microcytic Nl or ↓ Nl Nl ↓↓↓
Iron deficiency anemia (early phase)[2] Normochromic Normocytic Nl Nl
Lead poisoning[3]
  • 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[4] 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[5] Hypochromic Microcytic Nl Nl or ↓ Nl Nl NA
Thalassemia[6] 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[7]
  • History of using
+ Intrinsic Normochromic Normocytic ↑ but usually causes resolution within 4-7 days Nl to ↑ Nl
Pyruvate kinase deficiency[8] + 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[9] + Intrinsic Normochromic Normocytic Nl or moderately ↑ Nl Nl Nl or moderately ↑ Nl
HbC disease[10]
  • Glutamic acid–to-lysine mutation in β-globin
+ Intrinsic Normochromic Normocytic Nl Nl Nl Nl
Paroxysmal nocturnal hemoglobinuria[11][12] + Intrinsic Normochromic Normocytic Nl Nl NA
Hereditary spherocytosis[13] + 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[14][15] Associated with + Extrinsic Normochromic Normocytic Nl Nl
  • Helmet cells
Macroangiopathic hemolytic anemia[16] Associated with + Extrinsic Normochromic Normocytic Nl Nl
Autoimmune hemolytic anemia[17] Associated with:
  • Painful, blue fingers and toes with cold weather
+ Extrinsic Normochromic Normocytic Nl Nl
  • RBC agglutination
Aplastic anemia[18]
  • 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[19]
  • Impaired DNA synthesis
Anisochromic Macrocytic Nl Nl
Vitamin B12 deficiency[20] Anisochromic Macrocytic Nl Nl
Orotic aciduria[21]
  • Neurological manifestation
Anisochromic Macrocytic Nl Nl NA
Fanconi anemia[22]
  • 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[23] Mutations in:
  • RPL5
  • RPL11
  • RPL35A
  • RPS7
  • RPS10
  • RPS17
  • RPS19
  • RPS24
  • RPS26
Anisochromic Macrocytic Nl Nl Nl NA
Infections[24] Associated with + Extrinsic Normochromic Normocytic Nl Nl Nl
Chronic kidney disease[25] Normochromic Normocytic Nl/↑ Nl Nl
Liver disease[26]
  • Hepatitis
  • Binge drinking
  • Gall bladder disease
Anisochromic Macrocytic Nl Nl
Alcoholism[27] 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

Medical Therapy

If hemodynamic compromise is present, then immediate intervention is required which includes:

  • Administration of O2 as needed
  • Iron, folate, vitamin B12 supplements as necessary
  • IV fluids for maintenance of blood pressure
  • For hemoglobins <8 gm/dl, blood transfusions are indicated
  • Establishment of two large-bore IVs for cases of ongoing acute blood loss

There are many different treatments for anemia and the treatment depends on severity and the cause.

Iron deficiency from nutritional causes is rare in non-menstruating adults (men and post-menopausal women). The diagnosis of iron deficiency mandates a search for potential sources of loss such as gastrointestinal bleeding from ulcers or colon cancer. Mild to moderate iron deficiency anemia is treated by iron supplementation with ferrous sulfate or ferrous gluconate. Vitamin C may aid in the body's ability to absorb iron.

Vitamin supplements given orally (folic acid) or subcutaneously (vitamin B-12) will replace specific deficiencies.

In anemia of chronic disease, anemia associated with chemotherapy, or anemia associated with renal disease, some clinicians prescribe recombinant erythropoietin, epoetin alfa, to stimulate red cell production.

In severe cases of anemia, or with ongoing blood loss, a blood transfusion may be necessary. Transfusions can be complication by circulatory overload and iron overload so much be used with caution.

Contraindicated medications

Severe anemia is considered an absolute contraindication to the use of the following medications:

Blood Transfusions

  • Doctors attempt to avoid blood transfusion in general, since multiple lines of evidence point to increased adverse patient clinical outcomes with more intensive transfusion strategies. The physiological principle that reduction of oxygen delivery associated with anemia leads to adverse clinical outcomes is balanced by the finding that transfusion does not necessarily mitigate these adverse clinical outcomes.
  • In severe, acute bleeding, transfusions of donated blood are often lifesaving. Improvements in battlefield casualty survival is attributable, at least in part, to the recent improvements in blood banking and transfusion techniques.
  • Transfusion of the stable but anemic hospitalized patient has been the subject of numerous clinical trials, and transfusion is emerging as a deleterious intervention.
  • Four randomized controlled clinical trials have been conducted to evaluate aggressive versus conservative transfusion strategies in critically ill patients. All four of these studies failed to find a benefit with more aggressive transfusion strategies. [28][29][30][31]
  • In addition, at least two retrospective studies have shown increases in adverse clinical outcomes with more aggressive transfusion strategies.[32][33]
  • On the whole, these studies suggest that aggressive transfusions, at least for hospitalized patients, may at best not improve any clinical parameter, and at worst lead to adverse outcomes.
  • A recent report suggests that the culprit is the depletion of nitric oxide, an important vasodilator, in banked blood. The theory is that the transfusion of nitric oxide-depleted blood causes systemic vasoconstriction, and exacerbates hypoxia in tissues at risk.[34]

References

  1. Camaschella C (May 2015). "Iron-deficiency anemia". N. Engl. J. Med. 372 (19): 1832–43. doi:10.1056/NEJMra1401038. PMID 25946282.
  2. 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.
  3. Bain BJ (December 2014). "Lead poisoning". Am. J. Hematol. 89 (12): 1141. doi:10.1002/ajh.23852. PMID 25220013.
  4. 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.
  5. Roy CN (2010). "Anemia of inflammation". Hematology Am Soc Hematol Educ Program. 2010: 276–80. doi:10.1182/asheducation-2010.1.276. PMID 21239806.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. 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.
  11. Bunyaratvej A, Butthep P (January 1992). "Cytometric analysis of paroxysmal nocturnal hemoglobinuria erythrocytes". J Med Assoc Thai. 75 Suppl 1: 237–42. PMID 1402472.
  12. 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.
  13. 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.
  14. 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.
  15. 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.
  16. Westphal RG, Azen EA (May 1971). "Macroangiopathic hemolytic anemia due to congenital cardiovascular anomalies". JAMA. 216 (9): 1477–8. PMID 5108522.
  17. Hill QA (October 2015). "Autoimmune hemolytic anemia". Hematology. 20 (9): 553–4. doi:10.1179/1024533215Z.000000000401. PMID 26447931.
  18. 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.
  19. 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.
  20. Hunt A, Harrington D, Robinson S (September 2014). "Vitamin B12 deficiency". BMJ. 349: g5226. PMID 25189324.
  21. 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.
  22. 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.
  23. 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.
  24. 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.
  25. Drawz P, Rahman M (June 2015). "Chronic kidney disease". Ann. Intern. Med. 162 (11): ITC1–16. doi:10.7326/AITC201506020. PMID 26030647.
  26. 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.
  27. 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.
  28. Hébert PC, Wells G, Blajchman MA; et al. (1999). "A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group". N. Engl. J. Med. 340 (6): 409–17. PMID 9971864.
  29. Bush RL, Pevec WC, Holcroft JW (1997). "A prospective, randomized trial limiting perioperative red blood cell transfusions in vascular patients". Am. J. Surg. 174 (2): 143–8. PMID 9293831.
  30. Bracey AW, Radovancevic R, Riggs SA; et al. (1999). "Lowering the hemoglobin threshold for transfusion in coronary artery bypass procedures: effect on patient outcome". Transfusion. 39 (10): 1070–7. PMID 10532600.
  31. McIntyre LA, Fergusson DA, Hutchison JS; et al. (2006). "Effect of a liberal versus restrictive transfusion strategy on mortality in patients with moderate to severe head injury". Neurocritical care. 5 (1): 4–9. PMID 16960287.
  32. Corwin HL, Gettinger A, Pearl RG; et al. (2004). "The CRIT Study: Anemia and blood transfusion in the critically ill--current clinical practice in the United States". Crit. Care Med. 32 (1): 39–52. doi:10.1097/01.CCM.0000104112.34142.79. PMID 14707558.
  33. Vincent JL, Baron JF, Reinhart K; et al. (2002). "Anemia and blood transfusion in critically ill patients". JAMA. 288 (12): 1499–507. PMID 12243637.
  34. MEDICAL SCIENCES S-nitrosohemoglobin deficiency: A mechanism for loss of physiological activity in banked blood James D. Reynolds*, Gregory S. Ahearn{dagger}, Michael Angelo{dagger}, Jian Zhang{dagger}, Fred Cobb{dagger},{ddagger}, and Jonathan S. Stamler Published online before print October 11, 2007 Proc. Natl. Acad. Sci. USA, 10.1073/pnas.0707958104 Accessed 10/15/07