Anemia of prematurity differential diagnosis

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

Overview

Anemia of prematurity should be differentiated from anemia due to increased red blood cell destruction, increased blood loss, and decreased red blood cell production. It should also be differentiated from other causes of normocytic normochromic anemia.

Differential Diagnosis

Anemia of prematurity should be differentiated from anemia due to increased red blood cell destruction, increased blood loss, and decreased red blood cell production. Anemia of prematurity should also be differentiated from other causes of normocytic normochromic anemia.

Increased RBC destruction

Anemia of prematurity should be differentiated from anemia due to increased red blood cell destruction:

Decrease RBC production

Anemia of prematurity should be differentiated from anemia due to decreased red blood cell production:

Increase blood loss

Anemia of prematurity should be differentiated from anemia due to increased blood loss:

Normocytic Normochromic anemia

Differentiating Anemia of prematurity from other diseases

Anemia of prematurity 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
Anemia of prematurity Normochromic Normocytic Nl Nl Nl ↓↓↓ Predominant red blood cell precursors
Iron deficiency anemia Hypochromic Microcytic Nl or ↓ Nl Nl ↓↓↓
Iron deficiency anemia (early phase) Normochromic Normocytic Nl Nl
Lead poisoning
  • 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 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 Hypochromic Microcytic Nl Nl or ↓ Nl Nl NA
Thalassemia 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
  • History of using
+ Intrinsic Normochromic Normocytic ↑ but usually causes resolution within 4-7 days Nl to ↑ Nl
Pyruvate kinase deficiency + 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 + Intrinsic Normochromic Normocytic Nl or moderately ↑ Nl Nl Nl or moderately ↑ Nl
HbC disease
  • Glutamic acid–to-lysine mutation in β-globin
+ Intrinsic Normochromic Normocytic Nl Nl Nl Nl
Paroxysmal nocturnal hemoglobinuria + Intrinsic Normochromic Normocytic Nl Nl NA
Hereditary spherocytosis + 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 Associated with + Extrinsic Normochromic Normocytic Nl Nl
  • Helmet cells
Macroangiopathic hemolytic anemia Associated with + Extrinsic Normochromic Normocytic Nl Nl
Autoimmune hemolytic anemia Associated with:
  • Painful, blue fingers and toes with cold weather
+ Extrinsic Normochromic Normocytic Nl Nl
  • RBC agglutination
Aplastic anemia
  • 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
  • Impaired DNA synthesis
Anisochromic Macrocytic Nl Nl
Vitamin B12 deficiency Anisochromic Macrocytic Nl Nl
Orotic aciduria
  • Neurological manifestation
Anisochromic Macrocytic Nl Nl NA
Fanconi anemia
  • 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 Mutations in:
  • RPL5
  • RPL11
  • RPL35A
  • RPS7
  • RPS10
  • RPS17
  • RPS19
  • RPS24
  • RPS26
Anisochromic Macrocytic Nl Nl Nl NA
Infections Associated with + Extrinsic Normochromic Normocytic Nl Nl Nl
Chronic kidney disease Normochromic Normocytic Nl/↑ Nl Nl
Liver disease
  • Hepatitis
  • Binge drinking
  • Gall bladder disease
Anisochromic Macrocytic Nl Nl
Alcoholism Anisochromic Macrocytic Nl Nl
Disease Genetics History Symptoms Signs Hemolysis Intrinsic/

Extrinsic

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

References

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