Anemia of chronic disease differential diagnosis: Difference between revisions

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Revision as of 23:21, 29 November 2018

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

Overview

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

Differential Diagnosis

Concomitant iron deficiency

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

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

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

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

ACD: Normal to increased iron in bone marrow macrophages while erythroid precursors may show decreased to absent iron
Iron deficiency: No stainable iron in macrophages and erythroid precursors

Myelodysplastic syndromes

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

Sideroblastic anemias

Presence of ring sideroblasts on bone marrow examination

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

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

Endocrine disorders

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

Miscellaneous

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Disease	Genetics	Clinical manifestation					Lab findings
		History	Symptoms	Signs	Hemolysis	Intrinsic/ Extrinsic	Hb concentration	MCV	RDW	Reticulocytosis	Haptoglobin levels	Hepcidin	Iron studies					Specific finding on blood smear
		History	Symptoms	Signs	Hemolysis	Intrinsic/ Extrinsic	Hb concentration	MCV	RDW	Reticulocytosis	Haptoglobin levels	Hepcidin	Serum iron	Serum Tfr level	Transferrin or TIBC	Ferritin	Transferrin saturation	Specific finding on blood smear
Iron deficiency anemia^[6]	−	Menorrhagia GI loss GI surgery Pregnancy	Koilonychia Pica	Glossitis Cheilosis Dysphagia	−	−	Hypochromic	Microcytic	↑	Nl or ↓	Nl	Nl	↓	↑	↑	↓	↓↓↓	Central pallor
Iron deficiency anemia (early phase)^[7]	−	Pica Glossitis Cheilosis	Fatigue Headache	Koilonychia Conjunctival pallor Dry skin	−	−	Normochromic	Normocytic	↑	↓	Nl	Nl	↓	↑	↑	↓	↓	Pencil cells Elliptocytosis Hypochromasia
Lead poisoning^[8]	−	House painted with chipped paint	Burtonian lines Basophilic stippling Wrist drop Foot drop	Wrist drop Foot drop Burtonian lines	−	−	Hypochromic	Microcytic	Nl	Nl or ↓	Nl	Nl	Nl to ↓	Nl	Nl	Nl to ↓	−	RBCs retain aggregates of rRNA Basophilic stippling
Sideroblastic anemia^[9]	Defect in ALA synthase gene Autosomal dominant Autosomal recessive X-linked	Alcohol abuse Isoniazid use Chloramphenicol use Idiopathic	Seborrheic dermatitis Glossy Tongue Tingling	Patient present with symptoms of Vitamin B6, copper deficiency symptoms	−	−	Hypochromic	Microcytic	Nl	Nl or ↓	Nl	Nl	↑	Nl	Nl to ↓	↑	−	Ringed sideroblasts
Disease	Genetics	History	Symptoms	Signs	Hemolysis	Intrinsic/ Extrinsic	Hb concentration	MCV	RDW	Reticulocytosis	Haptoglobin levels	Hepcidin	Serum iron	Serum Tfr level	IBC	Ferritin	Transferrin saturation	Specific finding on blood smear
Anemia of chronic disease^[10]	−	Rheumatoid arthritis SLE Neoplasm Chronic kidney disease	Headache Shortness of breath	−	−	−	Hypochromic	Microcytic	Nl	Nl or ↓	Nl	↑	↓	Nl	↓	↑	−	NA
Thalassemia^[11]	α-thalassemia α- globin gene deletions Cis deletions Trans deletions β-thalassemia Point mutation in splice sites and promoter sequences	Associated with parvovirus B19	α-thalassemia Hydrops fetalis β-thalassemia Skeletal deformities Chipmunk facies	Hepatomegaly Splenomegaly	−	−	Hypochromic	Microcytic	Nl	Thalassemia trait: Nl or ↓ Thalassemia Syndromes: ↑	Nl	Nl	Nl to ↑	Nl	Nl	↑	Nl to ↑	Target cells Anisopoikilocytosis
G6PD deficiency^[12]	Defect in G6PD enzyme X-Linked recessive	History of using Sulfa drugs Antimalarials Fava Beans Infections	Back pain Hemoglobinuria	Back pain	+	Intrinsic	Normochromic	Normocytic	↑	↑ but usually causes resolution within 4-7 days	↓	↓	Nl to ↑	Nl	↑	↑	↑	RBC with Heinz bodies Bite cells Blister cells
Pyruvate kinase deficiency^[13]	Mutation in the PKLR and PKM gene Autosomal recessive	Gallstones	Hydrops fetalis Neonatal hyperbilirubinemia Iron overload Perinatal complications	Skin ulcers Splenomegaly	+	Intrinsic	Normochromic	Normocytic	↑	↑	↓	Nl	↑	Nl	Nl	↑	−	Prickle cells Polychromatophilic erythrocytes
Disease	Genetics	History	Symptoms	Signs	Hemolysis	Intrinsic/ Extrinsic	Hb concentration	MCV	RDW	Reticulocytosis	Haptoglobin levels	Hepcidin	Serum iron	Serum Tfr level	IBC	Ferritin	Transferrin saturation	Specific finding on blood smear
Sickle cell anemia^[14]	HbS point mutation causes a single amino acid replacement in β chain	High altitude Low Oxygen Acidosis African-American race Parvovirus B19 infection	Painful crisis Dactylitis Priapism Acute chest syndrome Avascular Necrosis Stroke Autosplenectomy Salmonella osteomyelitis	Dactylitis Priapism	+	Intrinsic	Normochromic	Normocytic	↑	↑	↓	Nl or moderately ↑	Nl	Nl	Nl or moderately ↑	↓	Nl	Increased erythropoiesis Howell-Jolly bodies Anisocytosis
HbC disease^[15]	Glutamic acid–to-lysine mutation in β-globin	Gallstone	Joint pains Increased risk of infections	Splenomegaly Cholelithiasis Avascular necrosis of the femoral head	+	Intrinsic	Normochromic	Normocytic	↑	↑	↓	Nl	Nl	Nl	Nl	↓	−	Hemoglobin crystals inside RBCs Target cells
Paroxysmal nocturnal hemoglobinuria^[16]^[17]	PIGA gene mutations Impaired synthesis of GPI anchor for decay-accelerating factor	Associated with aplastic anemia Thrombosis	Fatigue Chest pain Dyspnea on exertion Headache	Chronic hemolysis Hepatomegaly Ascites Papilledema Skin nodules	+	Intrinsic	Normochromic	Normocytic	↑	↑	↓	Nl	↓	Nl	↑	↓	−	NA
Hereditary spherocytosis^[18]	Mutations in Ankyrin, Band 3, Protein 4.2, and spectrin	Associated with parvovirus B19 Cholelithiasis Megaloblastic crisis	Aplastic crisis	Splenomegaly	+	Intrinsic	Normochromic	Normocytic	↑	↑	↓	Nl	↓	Nl	↑	Nl	−	Small, round RBCs with less surface area and no central pallor
Disease	Genetics	History	Symptoms	Signs	Hemolysis	Intrinsic/ Extrinsic	Hb concentration	MCV	RDW	Reticulocytosis	Haptoglobin levels	Hepcidin	Serum iron	Serum Tfr level	IBC	Ferritin	Transferrin saturation	Specific finding on blood smear
Microangiopathic hemolytic anemia^[19]^[20]	−	Associated with DIC TTP HUS SLE HELLP syndrome Hypertensive emergency	Purpura Confusion Aphasia Diplopia	Numbness of an arm or hand Jaundice Pale conjunctiva	+	Extrinsic	Normochromic	Normocytic	↑	↑	↓	Nl	↓	Nl	−	↑	−	Helmet cells
Macroangiopathic hemolytic anemia^[21]	Autoimmune	Associated with Prosthetic heart valves Aortic stenosis	Pallor Fatigue	Signs of anemia Complications of hemolysis Decreased vascular volume	+	Extrinsic	Normochromic	Normocytic	↑	↑	↓	Nl	↓	Nl	−	−	−	Spherocytes or schistocytes
Autoimmune hemolytic anemia^[22]	−	Associated with: SLE CLL Mycoplasma pneumonia	Painful blue fingers and toes on exposure to cold temperature Chest pain Chills Dizziness Tachycardia Headache Fatigue	Painful, blue fingers and toes with cold weather	+	Extrinsic	Normochromic	Normocytic	↑	↑	↓	Nl	↓	Nl	−	−	−	RBC agglutination
Aplastic anemia^[23]	Constitutive expression of Tbet Mutations in the perforin gene Mutations in SAP gene	Exposure to Radiation Drugs like Benzene, chloramphenicol, alkylating agents Viral infections like EBV, HIV, Hepatitis Fanconi anemia Idiopathic like Immune mediated, primary stem cell defect	Symptoms based on underlying condition	Short stature Cafe-au-lait spots Thumb defects Radial defects	−	−	Normochromic	Normocytic	↑	↓	Nl	Nl	↓	↓	Nl	↑	↓	Pancytopenia Fatty infiltration
Disease	Genetics	History	Symptoms	Signs	Hemolysis	Intrinsic/ Extrinsic	Hb concentration	MCV	RDW	Reticulocytosis	Haptoglobin levels	Hepcidin	Serum iron	Serum Tfr level	IBC	Ferritin	Transferrin saturation	Specific finding on blood smear
Folate deficiency^[24]	Impaired DNA synthesis	Alcohol consumption History of using drugs like methotrexate, trimethoprim, and phenytoin Low socioeconomic groups with poor nutrition Older people Pregnant and lactating women	No neurological symptoms vs B12 deficiency Odynophagia Angular stomatitis	Glossitis Signs of heart failure Anencephaly and spina bifida	−	−	Anisochromic	Macrocytic	↑	↓	Nl	Nl	↑	↑	↓	↑	↑	RBC macrocytosis Hypersegmented neutrophils Pancytopenia in severe cases
Vitamin B12 deficiency^[25]	Impaired DNA synthesis	Pernicious anemia Crohn's disease Gastrectomy Veganism Diphyllobothrium latum infection	Psychosis Insomnia Depression Cognitive slowing Restless leg syndrome	Neurological deficit Myelopathy Memory loss with reduced attention span Nystagmus Positive romberg sign Positive Lhermitte's sign	−	−	Anisochromic	Macrocytic	↑	↓	Nl	Nl	↑	↑	↓	↑	↑	Senile neutrophil Anisocytosis Ovalocytes
Orotic aciduria^[26]	Autosomal recessive Deficiency of enzyme UMPS	Episodic vomiting Rhabdomyolysis	Coma Gastrointestinal manifestation	Neurological manifestation	−	−	Anisochromic	Macrocytic	↑	↓	Nl	Nl	↑	↑	↓	↑	↑	NA
Fanconi anemia^[27]	Autosomal recessive X-linked recessive	History of anemia at age 16	Hypopigmentation Cafe-au-lait patches Radial ray anomaly	Significant for bilateral short thumbs	−	−	Anisochromic	Macrocytic	↑	↓	Nl	Nl	↑	↑	↓	↑	↑	Nl appearing WBC, RBC and Platelets But the number is greatly reduced
Disease	Genetics	History	Symptoms	Signs	Hemolysis	Intrinsic/ Extrinsic	Hb concentration	MCV	RDW	Reticulocytosis	Haptoglobin levels	Hepcidin	Serum iron	Serum Tfr level	IBC	Ferritin	Transferrin saturation	Specific finding on blood smear
Diamond-Blackfan anemia^[28]	Mutations in: RPL5 RPL11 RPL35A RPS7 RPS10 RPS17 RPS19 RPS24 RPS26	Associated with myelodysplastic syndrome Increased risk of AML	Pale skin Sleepiness Heart murmurs	Triphalangeal thumbs Short stature Microcephaly Hypertelorism Ptosis Micrognathia	−	−	Anisochromic	Macrocytic	Nl	↓	Nl	Nl	↑	↑	↓	↑	↑	NA
Infections^[29]	−	Associated with Malaria Babesia	Fever	Fever Signs of shock Headache	+	Extrinsic	Normochromic	Normocytic	↑	↑	↓	Nl	Nl	Nl	−	−	−	Trophozoite Maltese crosses
Chronic kidney disease^[30]	−	Pericarditis Encephalopathy Rectal incontinence Decreased libido Restless leg syndrome	Polyuria Hematuria Edema	Hypertension	−	−	Normochromic	Normocytic	↑	Nl/↑	Nl	↑	↓	−	↓	↑	↓	Nl
Liver disease^[31]	−	Hepatitis Binge drinking Gall bladder disease	Jaundice Abdominal pain Itchy skin	Ascites Right upper quadrant pain Hepatomegaly Swelling in the legs Ankle swelling	−	−	Anisochromic	Macrocytic	↑	↑	Nl	Nl	↑	↑	↓	↑	↑	Round macrocytes Target macrocytes
Alcoholism^[32]	−	History of increased alcohol intake Folic acid deficiency	Memory impairment Nausea Sweating	Truncal obesity Asterixis Encephalopathy Spider angiomas Hematemesis Gynecomastia	−	−	Anisochromic	Macrocytic	↑	↑	Nl	Nl	↑	↑	↓	↑	↑	Oval macrocytes Hypersegmented neutrophils
Disease	Genetics	History	Symptoms	Signs	Hemolysis	Intrinsic/ Extrinsic	Hb concentration	MCV	RDW	Reticulocytosis	Haptoglobin levels	Hepcidin	Serum iron	Serum Tfr level	IBC	Ferritin	Transferrin saturation	Specific finding on blood smear

References

↑ Archer NM, Shmukler BE, Andolfo I, Vandorpe DH, Gnanasambandam R, Higgins JM, Rivera A, Fleming MD, Sachs F, Gottlieb PA, Iolascon A, Brugnara C, Alper SL, Nathan DG (December 2014). "Hereditary xerocytosis revisited". Am. J. Hematol. 89 (12): 1142–6. doi:10.1002/ajh.23799. PMC 4237618. PMID 25044010.
↑ Brugnara C (October 2003). "Iron deficiency and erythropoiesis: new diagnostic approaches". Clin. Chem. 49 (10): 1573–8. PMID 14500582.
↑ Thomas C, Thomas L (July 2002). "Biochemical markers and hematologic indices in the diagnosis of functional iron deficiency". Clin. Chem. 48 (7): 1066–76. PMID 12089176.
↑ Theurl I, Mattle V, Seifert M, Mariani M, Marth C, Weiss G (May 2006). "Dysregulated monocyte iron homeostasis and erythropoietin formation in patients with anemia of chronic disease". Blood. 107 (10): 4142–8. doi:10.1182/blood-2005-08-3364. PMID 16434484.
↑ DeLoughery TG (October 2014). "Microcytic anemia". N. Engl. J. Med. 371 (14): 1324–31. doi:10.1056/NEJMra1215361. PMID 25271605.
↑ Camaschella C (May 2015). "Iron-deficiency anemia". N. Engl. J. Med. 372 (19): 1832–43. doi:10.1056/NEJMra1401038. PMID 25946282.
↑ 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.
↑ Bain BJ (December 2014). "Lead poisoning". Am. J. Hematol. 89 (12): 1141. doi:10.1002/ajh.23852. PMID 25220013.
↑ 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.
↑ Roy CN (2010). "Anemia of inflammation". Hematology Am Soc Hematol Educ Program. 2010: 276–80. doi:10.1182/asheducation-2010.1.276. PMID 21239806.
↑ 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.
↑ 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.
↑ 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.
↑ 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.
↑ 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.
↑ Bunyaratvej A, Butthep P (January 1992). "Cytometric analysis of paroxysmal nocturnal hemoglobinuria erythrocytes". J Med Assoc Thai. 75 Suppl 1: 237–42. PMID 1402472.
↑ 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.
↑ 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.
↑ 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.
↑ 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.
↑ Westphal RG, Azen EA (May 1971). "Macroangiopathic hemolytic anemia due to congenital cardiovascular anomalies". JAMA. 216 (9): 1477–8. PMID 5108522.
↑ Hill QA (October 2015). "Autoimmune hemolytic anemia". Hematology. 20 (9): 553–4. doi:10.1179/1024533215Z.000000000401. PMID 26447931.
↑ 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.
↑ 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.
↑ Hunt A, Harrington D, Robinson S (September 2014). "Vitamin B12 deficiency". BMJ. 349: g5226. PMID 25189324.
↑ 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.
↑ 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.
↑ 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.
↑ 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.
↑ Drawz P, Rahman M (June 2015). "Chronic kidney disease". Ann. Intern. Med. 162 (11): ITC1–16. doi:10.7326/AITC201506020. PMID 26030647.
↑ 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.
↑ 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.

Template:WikiDoc Sources

[pmid25044010-1] Archer NM, Shmukler BE, Andolfo I, Vandorpe DH, Gnanasambandam R, Higgins JM, Rivera A, Fleming MD, Sachs F, Gottlieb PA, Iolascon A, Brugnara C, Alper SL, Nathan DG (December 2014). "Hereditary xerocytosis revisited". Am. J. Hematol. 89 (12): 1142–6. doi:10.1002/ajh.23799. PMC 4237618. PMID 25044010.

[pmid14500582-2] Brugnara C (October 2003). "Iron deficiency and erythropoiesis: new diagnostic approaches". Clin. Chem. 49 (10): 1573–8. PMID 14500582.

[pmid12089176-3] Thomas C, Thomas L (July 2002). "Biochemical markers and hematologic indices in the diagnosis of functional iron deficiency". Clin. Chem. 48 (7): 1066–76. PMID 12089176.

[pmid16434484-4] Theurl I, Mattle V, Seifert M, Mariani M, Marth C, Weiss G (May 2006). "Dysregulated monocyte iron homeostasis and erythropoietin formation in patients with anemia of chronic disease". Blood. 107 (10): 4142–8. doi:10.1182/blood-2005-08-3364. PMID 16434484.

[pmid25271605-5] DeLoughery TG (October 2014). "Microcytic anemia". N. Engl. J. Med. 371 (14): 1324–31. doi:10.1056/NEJMra1215361. PMID 25271605.

[pmid25946282-6] Camaschella C (May 2015). "Iron-deficiency anemia". N. Engl. J. Med. 372 (19): 1832–43. doi:10.1056/NEJMra1401038. PMID 25946282.

[pmid24972460-7] De Andrade Cairo RC, Rodrigues Silva L, Carneiro Bustani N, Ferreira Marques CD (June 2014). "Iron deficiency anemia in adolescents; a literature review". Nutr Hosp. 29 (6): 1240–9. doi:10.3305/nh.2014.29.6.7245. PMID 24972460.

[pmid25220013-8] Bain BJ (December 2014). "Lead poisoning". Am. J. Hematol. 89 (12): 1141. doi:10.1002/ajh.23852. PMID 25220013.

[pmid25064706-9] Bottomley SS, Fleming MD (August 2014). "Sideroblastic anemia: diagnosis and management". Hematol. Oncol. Clin. North Am. 28 (4): 653–70, v. doi:10.1016/j.hoc.2014.04.008. PMID 25064706.

[pmid21239806-10] Roy CN (2010). "Anemia of inflammation". Hematology Am Soc Hematol Educ Program. 2010: 276–80. doi:10.1182/asheducation-2010.1.276. PMID 21239806.

[pmid25500521-11] Zainal NZ, Alauddin H, Ahmad S, Hussin NH (December 2014). "α-Thalassemia with Haemoglobin Adana mutation: prenatal diagnosis". Malays J Pathol. 36 (3): 207–11. PMID 25500521.

[pmid24372186-12] Luzzatto L, Seneca E (February 2014). "G6PD deficiency: a classic example of pharmacogenetics with on-going clinical implications". Br. J. Haematol. 164 (4): 469–80. doi:10.1111/bjh.12665. PMC 4153881. PMID 24372186.

[pmid26087744-13] Grace RF, Zanella A, Neufeld EJ, Morton DH, Eber S, Yaish H, Glader B (September 2015). "Erythrocyte pyruvate kinase deficiency: 2015 status report". Am. J. Hematol. 90 (9): 825–30. doi:10.1002/ajh.24088. PMC 5053227. PMID 26087744.

[pmid25431087-14] Singh PC, Ballas SK (March 2015). "Emerging drugs for sickle cell anemia". Expert Opin Emerg Drugs. 20 (1): 47–61. doi:10.1517/14728214.2015.985587. PMID 25431087.

[pmid25335812-15] Lemonne N, Billaud M, Waltz X, Romana M, Hierso R, Etienne-Julan M, Connes P (2016). "Rheology of red blood cells in patients with HbC disease". Clin. Hemorheol. Microcirc. 61 (4): 571–7. doi:10.3233/CH-141906. PMID 25335812.

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@@ Line 296: / Line 296: @@
 * 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="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
@@ Line 385: / Line 385: @@
 ! 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
+* HbS [[point mutation]] causes a single [[Amino acid|amino acid]] replacement in β chain
 | align="left" style="background:#F5F5F5;" |
 * [[High altitude]]


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