Anemia

2025-07-09
15:12
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ID: 15934

Disorders of Red blood cells

Anemia

Disorders of Iron metabolism and heme synthesis
- Iron deficiency and related disorders
- Sidroblastic anemia
- Hemochromatosis
- Porphyrias

Hemolytic anemia

Intrinsic red blood cell abnormalities
- Sickle cell anemia and other sickling syndroms
- Thalassemias and related disorders
- Pyruvate kinase deficiency (PKD)
- Glucose-6-phosphate dehydrogenase (G6PD) deficiency
- Hereditary spherocytosis and elliptocytosis
- Paroxymal nocturnal hemoglobinuria (PNH)

Disorders of extrinsic to the red blood cells
- autoimmunehemolytic anemia (AIHA)
Cold antibody
Warm antibody
Drug and toxin-induced
Hemolytic uremic syndrome
Paroxysmal cold hemoglobinuria
Thrombotic thrombocytopenic purpura

Hereditary disorders of hemoglobin structure and synthesis
Sickle cell anemia and other sickling syndroms
Thalassemias and related disorders
Hemoglobins with alterd oxygen affinity, unstable hemoglobins, M-hemoglobins and dyshemoglobinemias

Other red cell disorders
- Megaloblastic anemias: Disorders of impaired DNA synthesis
- Inherited aplastic anemia syndromes
- Acquired aplastic anemia
- Red cell aplasia: acquired and congenital disorders
- Congenital dyserythropoietic anemia
- Anemia secondary to chronic disease and systemic disorders
- Anemia during pregnancy and the postpartum period
- Anemias unique to the fetus and neonate
- Erythrocytosis

Anemia

General information:

Anemia has been defined as a reduction in one or more of the major red blood cell (RBC) measurements obtained as a part of the complete blood count (CBC): hemoglobin concentration, hematocrit (HCT), or RBC count According to age, sex and physiological conditions. In practice, however, a low hemoglobin concentration or a low hematocrit is most widely employed for this purpose.

Disorders of Iron metabolism and heme synthesis
- Iron deficiency and related disorders

Definition:

Iron deficiency anemia is the most common type of anemia in which usually intake of iron is not enough. Women with heavy menstrual periods, pregnant, people with major surgery or gastrointestinal disease such as celiac disease, IBD, vegetarians and children are at risk for iron-deficiency anemia. Red blood cells tend to be microcytic and hypochromic and iron stores are low, by serum level ferritin and low serum total iron-binding capacity. Symptoms of iron deficiency of anemia are associated with reduced oxygen delivery and include: fatigue, chest pain, weakness, rapid heartbeat, headache, picophagi, fragile nails and hair loss. (See the algorithm)

Lab tests:

CBC with Platelet Count and Automated Differential

Reticulocytes, Percent and Number

Blood Smear with Interpretation

Serum Iron and Iron Binding Capacity

Ferritin

Vitamin B12

Hemoglobin Electrophoresis

Soluble transferrin Receptor

Erythrocyte Porphyrin (EP)

References:

Sidroblastic anemia

Definition:

Sidroblastic anemias are a various group of erythropoietic disorders in which iron deposits in erythroblast mitochondria and lead to different abnormality in heme synthesis and mitochondrial function. These iron-filled mitochondria bordering the nucleus of red blood cell and give the ring shape under the microscope. It can be classified in to congenital and acquired forms and both types have distinct causes, treatment and prognoses.

Panel test:

Genetics test:

ALAS2– X-linked sideroblastic anemia (XLSA)
SLC25A38,HSPA9, and GLRX5 (Autosomal recessive nonsyndromic sideroblastic anemias)
ABCB7– XLSA with ataxia (XLSA/A)
NDUFB11– X-linked sideroblastic anemia with variable syndromic features such as short stature, developmental delay or myopathy
TRNT1– Sideroblastic anemia with immunodeficiency, periodic fevers, and developmental delay (SIFD)
PUS1, YARS2, NDUFB11, MT-ATP6, and LARS2– Myopathy, acidosis, and sideroblastic anemia (MLASA) and MLASA variants
SLC19A2– Thiamine-responsive megaloblastic anemia (TRMA)
FECH– Erythropoietic protoporphyria (EPP)
Mitochondrial DNA deletions and rearrangements – Pearson marrow-pancreas syndrome

In the MDS disorders with ring sideroblasts, acquired mutations in two genes are very common:

SF3B1– All three MDS/MPN disorders with ring sideroblasts
JAK2 V617F mutation – MPN with ring sideroblasts and thrombocytosis

Lab tests:

CBC with Platelet Count and Automated Differential

Reticulocytes, Percent and Number

Blood Smear with Interpretation

Bone marrow examination (for ring sideroblasts)

Iron and Iron Binding Capacity

Ferritin

Vitamin B12

Hemoglobin Electrophoresis

Soluble transferrin Receptor

Erythrocyte Porphyrin (EP)

References:

Bergmann AK, Campagna DR, McLoughlin EM, et al. Systematic molecular genetic analysis of congenital sideroblastic anemia: evidence for genetic heterogeneity and identification of novel mutations. Pediatr Blood Cancer 2010; 54:273.
Liu G, Guo S, Kang H, et al. Mutation spectrum in Chinese patients affected by congenital sideroblastic anemia and a search for a genotype-phenotype relationship. Haematologica 2013; 98:e158.
Ducamp S, Kannengiesser C, Touati M, et al. Sideroblastic anemia: molecular analysis of the ALAS2 gene in a series of 29 probands and functional studies of 10 missense mutations. Hum Mutat 2011; 32:590.
Bottomley SS. Sideroblastic anemias. In: Wintrobe’s Clinical Hematology, 13th ed, Greer JP, Arber DA, Glader B, et al. (Eds), Lippincott, Williams and Wilkins, Philadelphia 2014. p.643.

Hemochromatosis

Definition:

Hemochromatosis is a disorder in which intestinal iron absorption is increased and overload of iron can build up in the organs and cause organ failure. There are two types of hemochromatosis: primary is caused by a defect in the certain genes that control absorption of iron. Secondary hemochromatosis is the result of another chronic disorders.

Panel test:

Genetics test:

HFE (type I): is very common in patients.
Juvenile hemochromatosis (type II):
Type IIA: Mutation in HJV
Type IIB: Mutation in HAMP
Transferrin receptor 2 mutation (type III)
Ferroportin mutations (type IV):
Macrophage type: Loss of function
Hepati type: Gain of function

Lab tests:

CBC and Automated Differential

Blood Smear with Interpretation

Iron and Iron Binding Capacity

Serum Ferritin

Vitamin B12

Soluble transferrin Receptor

Transferrin saturation

Liver function tests

References:

ACG Clinical Guideline: Hereditary Hemochromatosis Kris V. Kowdley, MD, FACG1, Kyle E. Brown, MD, MSc2,3,4, Joseph Ahn, MD, MS, MBA, FACG (GRADE Methodologist)5 and Vinay Sundaram, MD, MSc. Am J Gasroenterol 2019; 114: 1202-1218.

Porphyrias

Definition:

Porphyria is a group of blood disorders in which altered activities of enzymes involved the heme biosynthesis due to accumulation of porphyrin in the body. Porhyrias are classified to acute porphyrias and cutaneous porphyrias depending on the primary symptoms.

Lab tests:

Urine Porphobilinogen (PBG)- Acute attack symptomes

Total porphyrins in plasma or urine- blistering skin photosensitivity with or without acute symptomes

Erythrocyte total protopophyrin- in nonblistering photosensitivity

Fecal porphyrins

Urine ALA

HMBS activity (poephovilinogen deaminase) in RBCs

Genetics test:

ALAS2, ALAD, HMBS, UROS, UROD, CPOX, PPOX, FECH

Algorithm:

References:

Stölzel, U., Doss, M. O., & Schuppan, D. (2019). Clinical Guide and Update on Porphyrias. Gastroenterology. 2019; 1-17.

Hemolytic anemia

General information:

Hemolysis refers to lysis (destruction) of red blood cells (RBCs). Hemolytic anemia refers to anemia caused by hemolysis; some patients with hemolysis in whom production of new RBCs can be increased to compensate for RBC destruction may not be anemic. Hemolysis and hemolytic anemia can be classified in several ways, all of which are helpful in the patient evaluation and management:

Intrinsic red blood cell abnormalities

definition:

Defects intrinsic to the RBC that can cause hemolysis involve abnormalities of the RBC membrane, cell metabolism, or hemoglobin structure. Abnormalities include hereditary cell membrane disorders, acquired cell membrane disorders), disorders of RBC metabolism). Quantitative and functional abnormalities of certain RBC membrane proteins (alpha- and beta-spectrin, protein 4.1, F-actin, ankyrin) cause hemolytic anemias.

Sickle cell anemia and other sickling syndromes

Definition:

Homozygosity for a unique hemoglobin gene mutation (HBB glu6val, GAG —> GTG, sickle hemoglobin, HbS), located on chromosome 11, causes sickle cell anemia (SCA). Upon deoxygenation, HbS molecules polymerize into intracellular fibers, forming a high molecular weight gel and causing the sickle cell deformity. This process initiates an elaborate and incompletely understood pathophysiological cascade that includes injury to the sickle red cell; intravascular and extravascular hemolysis; adhesive interactions among sickle cells, endothelial cells, other blood cells, and plasma factors; reperfusion injury; and inflammation. As a result of this cascade, vital tissues are injured, impairing their function, causing localized pain (ie, the sickle cell vaso-oclusive crisis) and, in many cases, premature death for the affected individual.

Lab tests:

CBC and Automated Differential

Blood Smear with Interpretation

Solubility testing

Hemoglobin electrophoresis

DNA testing (Prenatal diagnosis)

Thalassemias and related disorders

Definition:

Thalassemia refers to a group of inherited hemoglobinopathies where there is a quantitative defect in the production of alpha globin or beta globin chains. The resulting imbalance in the ratio of alpha to beta globin chains leads to precipitation of the unpaired chains, which in turn causes destruction of developing red blood cell precursors in the bone marrow that can lead to ineffective erythropoiesis, anemia, and iron overload.

Lab tests:

CBC and Automated Differential

Blood Smear with Interpretation

Iron and TIBC

Hemoglobin electrophoresis

DNA testing (Prenatal diagnosis)

Pyruvate kinase deficiency (PKD)

Definition:

Pyruvate kinase (PK) deficiency is an inherited (autosomal recessive) red blood cell (RBC) enzyme disorder that causes chronic hemolysis. It is the second most common RBC enzyme defect but is the commonest cause of hemolytic anemia from an RBC enzyme deficiency.

Lab tests:

CBC and Automated Differential

Blood Smear with Interpretation

Reticulocyte count

Iron and TIBC

LDH

Indirect bilirubin

Haptoglobin

Direct and Indirect antiglobulin (coombs) test

Alanine aminotransferase (ALT)

Other tests can be helpful:

Hemoglobin electrophoresis

RBC enzyme assay

Flow cytometry

Cold agglutinins

Osmotic fragility

Glucose-6-phosphate dehydrogenase (G6PD) deficiency

Definition:

Glucose-6-phosphate dehydrogenase (G6PD) deficiency, an X-linked disorder, is the most common enzymatic disorder of red blood cells in humans, affecting more than 400 million people worldwide. The clinical expression of G6PD variants encompasses a spectrum of hemolytic syndromes. Affected patients are most often asymptomatic, but many patients have episodic anemia, while a few have chronic hemolysis. With most G6PD variants, hemolysis is induced in children and adults by the sudden destruction of older, more deficient erythrocytes after exposure to drugs having a high redox potential (including the antimalarial drug primaquine and certain sulfa drugs) or to fava beans, selected infections, or metabolic abnormalities. However, in the neonate with G6PD deficiency, decreased bilirubin elimination may play an important role in the development of jaundice.

Lab tests:
CBC and Automated Differential
Blood Smear with Interpretation
Reticulocyte count
Evaluation of G6PD
Auto hemolysis test
Heinz body stain
LDH (lactate dehydrogenase)
Indirect and direct bilirubin level
Serum Haptoglobin
Urinalysis
Urinary hemosiderin

Hereditary Elliptocytosis syndromes:

Definition:

HE syndromes are a group of inherited erythrocyte disorders defined by elliptical RBC on the peripheral blood smear. The clinical symptoms are extremely variable, from asymptomatic condition to a moderate hemolytic anemia. The HE is occurred by abnormalities of spectrin, Ankyrin, Protein 4.2, Protein 4.1, Band 3 protein and Glycophorin C.

Lab tests:

CBC and Automated Differential

Blood Smear with Interpretation

Iron and Iron Binding Capacity

Serum Ferritin

Reticulocyte count

LDH (lactate dehydrogenase)

Haptoglobin

Direct antiglobulin test (coombs)

Analysis of RBC proteins

Osmotic gradient ektacytometry

Paroxymal nocturnal hemoglobinuria (PNH)

Definition:

Paroxymal nocturnal hemoglobinuria (PNH) is a rare acquired disorder characterized by intravascular hemolysis and hemoglobinuria. Leukopenia, thrombocytopenia, arterial and venous thromboses and episodic crises are common. Subsequent investigations have clarified much of the pathogenesis of the disease, including the genetic defect and the mechanism of complement-mediated hemolysis.

Lab tests:

CBC and Automated Differential

Blood Smear with Interpretation

Reticulocyte count

LDH (lactate dehydrogenase)

Coombs test

Indirect and direct bilirubin level

Urinalysis

Flow cytometry test

References:

Disorders extrinsic to the red blood cells

Definition:

It is caused by factors outside the red blood cell, such as antibodies from an autoimmune disorder, burns, or medications. In these conditions, red blood cells are usually healthy when they are produced by the bone marrow, but later they are destroyed directly in the bloodstream or get prematurely trapped and recycled in the spleen.

Autoimmunehemolytic anemia (AIHA)

Definition:

Autoimmune hemolytic anemia (AIHA) is a collection of disorders characterized by the presence of autoantibodies (warm or cold antibodies) that bind to the patient’s own erythrocytes, leading to premature red cell destruction (ie, hemolysis) and, when the rate of hemolysis exceeds the ability of the bone marrow to replace the destroyed red cells, to anemia and its attendant signs and symptoms. Hemolysis is usually extravascular.

Cold agglutinin disease

Definition:

Cold agglutinin disease is relatively uncommon in children, amounting to approximately 10 percent of cases, most commonly occurring after Mycoplasma pneumoniae or Epstein-Barr virus (EBV) infection. In this disorder, immunoglobulin M (IgM) autoantibodies bind erythrocyte I/i antigens at colder temperatures and fix complement, which leads to anemia, either due to complement-mediated intravascular hemolysis or immune-mediated extravascular clearance, mainly by hepatic macrophages.

Warm – reactive AIHA

Definition:

The most common form of primary AIHA in children, accounting for 60 to 90 percent of cases, involves warm-reactive autoantibodies, usually immunoglobulin G (IgG), that bind preferentially to the red cells at 37°C, leading to extravascular hemolysis mainly in the spleen, with resulting anemia, jaundice and, occasionally, splenomegaly. In some cases, IgG is present in sufficient quantity and proximity to fix complement, resulting in features of concomitant intravascular hemolysis.

Paroxysmal cold hemoglobinuria

Definition:

Paroxysmal cold hemoglobinuria (PCH) is an AIHA seen almost exclusively in children, most commonly after a viral-like illness. PCH is characterized by IgG autoantibodies that bind preferentially at colder temperatures, fix complement efficiently, and cause intravascular hemolysis with hemoglobinemia, hemoglobinuria, and anemia. PCH is discussed in greater detail separately.

Drug and toxin-induced

Definition:

Although not common in children, erythrocyte autoantibodies and hemolysis in association with drug exposure may cause secondary AIHA. This process was described classically after therapy with methyldopa, but red cell autoantibodies have been reported in association with many different pharmaceutical agents. Medications that are particularly important in causing AIHA in children include penicillins, cephalosporins, tetracycline, erythromycin, probenecid, acetaminophen, and ibuprofen. The mechanism of drug-induced hemolytic anemia typically results from generation of autoantibodies, although the drug may be required to form a hapten or even a ternary complex with the erythrocyte.

Toxins which can induced hemolytic anemia are: Lead, cooper (Wilson disease), Interferon alfa, insect, spider and snake bites.

Thrombotic thrombocytopenic purpura

Definition:

Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy caused by severely reduced activity of the von Willebrand factor-cleaving protease ADAMTS13. It is characterized by small-vessel platelet-rich thrombi that cause thrombocytopenia and microangiopathic hemolytic anemia (MAHA). Some patients may have neurologic abnormalities, mild renal insufficiency, and low-grade fever. Most cases of TTP are acquired, caused by autoantibody inhibition of ADAMTS13 activity. Hereditary TTP, caused by ADAMTS13 gene mutations, is much less common.

Hemolytic uremic syndrome

Definition:

The hemolytic uremic syndrome (HUS) is defined by the simultaneous occurrence of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. It is one of the main causes of acute kidney injury in children. Although all pediatric cases exhibit the classic triad of findings that define HUS, there are a number of various etiologies of HUS that result in differences in presentation, management, and outcome

Lab tests:

CBC and Automated Differential

Blood Smear with Interpretation

Reticulocyte count

LDH (lactate dehydrogenase)

Indirect and direct bilirubin level

Haptoglobin

Free hemoglobin in plasma, serum or urine

Urinalysis (hemosiderin)

Evaluation of G6PD

Direct and indirect antiglobulin test (coombs)

Hemolytic disease of the fetus and newborn

Definition:

Hemolytic disease of the fetus and newborn (HDFN), also known as alloimmune HDFN or erythroblastosis fetalis, is caused by the destruction of red blood cells (RBCs) of the neonate or fetus by maternal immunoglobulin G (IgG) antibodies. These antibodies are produced when fetal erythrocytes, which express an RBC antigen not expressed in the mother, gain access to the maternal circulation.

Lab tests:

CBC and Automated Differential

Blood Smear with Interpretation

Reticulocyte count

Coombs test (Direct and indirect antiglobulin test)

Evaluation of G6PD

Indirect and direct bilirubin level

Urinalysis

References:

Oski FA, Brugnara C, Nathan DG. A diagnostic approach to the anemic patient. In: Nathan and Oski’s Hematology of Infancy and Childhood, 6th, Nathan DG, Orkin SH, Ginsberg D, Look AT (Eds), WB Saunders, Philadelphia 2003. p.409.
Bottomley SS. Sideroblastic anemias. In: Wintrobe’s Clinical Hematology, 13th ed, Greer JP, Arber DA, Glader B, et al. (Eds), Lippincott, Williams and Wilkins, Philadelphia 2014. p.643.

Hereditary disorders of hemoglobin structure and synthesis
Sickle cell anemia and other sickling syndroms

Definition:

Lab tests:
CBC and Automated Differential
Blood Smear with Interpretation
Solubility testing
Hemoglobin electrophoresis
DNA testing (Prenatal diagnosis)

References:

Bunn HF. Pathogenesis and treatment of sickle cell disease. N Engl J Med 1997; 337:762.

Thalassemias and related disorders

Definition:

Lab tests:

CBC and Automated Differential

Blood Smear with Interpretation

Iron and TIBC

Hemoglobin electrophoresis

DNA testing (Prenatal diagnosis)

References:

http://www.thalassaemia.org.cy/uploads/1466152679tifguidelinesformanagementfinalmerged.pdf (Accessed on May 12, 2017).
http://thalassemia.com/#gsc.tab=0 (Accessed on May 12, 2017).
Rachmilewitz EA, Giardina PJ. How I treat thalassemia. Blood 2011; 118:3479.
Higgs DR, Engel JD, Stamatoyannopoulos G. Thalassaemia. Lancet 2012; 379:373.
Liu C, Grossman BJ. Red blood cell transfusion for hematologic disorders. Hematology Am Soc Hematol Educ Program 2015; 2015:454.

Hemoglobins with alterd oxygen affinity, unstable hemoglobins, M-hemoglobins and dyshemoglobinemias

Definition:

Over 1000 different mutations of the globin chains of the human hemoglobin molecule have been discovered. They are classified according to the type of mutation (eg, insertion, deletion, base change), the affected globin subunit (eg, alpha chain, beta chain), and by the clinical and hematologic phenotype. Abnormal hemoglobins can be detected by a number of protein-based and DNA-based methods. High frequency mutations are: HbS, C, E and low frequency mutations are HbDLosAngeles, HbG-Philadelphia, Hb Hasharon. Hb H is composed of a tetramer of normal Beta chains in which there is markedly decreased production of normal alpha chain. Other abnormal hemoglobines are: Hb Koln (ustable hemoglobins), Hb Chesapeake (high oxygen affinity hemoglobins), Hb Kansas (Low oxygen affinity hemoglobins), Hb M (methemoglobin in which heme iron is locked in the ferric form), Hb constant spring and Hb O-Arab.

Lab tests:

CBC and Automated Differential

Blood Smear with Interpretation

Iron and TIBC

Hemoglobin electrophoresis

DNA testing (Prenatal diagnosis)

References:

Disorders of Hemoglobin: Genetics, Pathophysiology, Clinical Management, Forget BG, Higgs DR, Nagel RL, et al. (Eds), Cambridge University Press, UK 1999.
http://globin.cse.psu.edu (Accessed on April 02, 2010).
Charache S, Weatherall DJ, Clegg JB. Polycythemia associated with a hemoglobinopathy. J Clin Invest 1966; 45:813.

Other red cell disorders
- Megaloblastic anemias: Disorders of impaired DNA synthesis

Definition:

megaloblastic anemia is a form of macrocytic anemia in which nucleic acid metabolism is impaired, leading to reduced efficiency of cell division and nuclear-cytoplasmic dyssynchrony. Causes of megaloblastic anemia include deficiency of vitamin B12, folate, or copper, as well as a number of medications that interfere with purine or pyrimidine metabolism.

Lab tests:

CBC and Automated Differential

Blood Smear with Interpretation

Reticulocyte count

B12 vitamin

Iron and TIBC

Bone marrow examination

LDH

References:

Inherited aplastic anemia syndromes

Definition:

Aplastic anemia (AA) is a life-threatening form of bone marrow failure which, if untreated, is associated with very high mortality. AA refers to pancytopenia in association with bone marrow hypoplasia/aplasia, most often due to immune injury to multipotent hematopoietic stem cells. The term “aplastic anemia” is a misnomer because the disorder is characterized by pancytopenia rather than anemia alone. The four major inherited causes for AA in children are:

Fanconi anemia (FA)
Dyskeratosis congenita (DC)
Shwachman-Diamond syndrome (SDS)
Congenital amegakaryocytic thrombocytopenia (CAMT)

Lab tests:

CBC and Automated Differential

Blood Smear with Interpretation

Bone marrow aspiration and biopsy

Serum B12 vitamin

Erythrocyte folate level

Serologic tests for viruses associated with AA

Chromosomal breakage testing with mitomycin c (MMC) or diepoxybutane (DEB) screening for Fanconi anemia

Telomere length measurements for Dyskeratosis congenita

References:

Alter BP. Inherited Bone Marrow Failure Syndromes. In: Nathan and Oski’s Hematology of Infancy and Childhood, Nathan DG, Orkin SH, Ginsburg D, Look AT (Eds), W.B. Saunders, Philadelphia 2003. p.280.
Young NS. Acquired aplastic anemia. Ann Intern Med 2002; 136:534.
Brodsky RA, Jones RJ. Aplastic anaemia. Lancet 2005; 365:1647.

Acquired aplastic anemia

Definition:

Acquired AA, characterized by pancytopenia and hypocellular bone marrow in the absence of abnormal infiltrates and without increased reticulin, accounts for most cases of AA in children and young adults. The peripheral blood typically exhibits pancytopenia, reticulocytopenia, and normocytic or macrocytic erythrocytes. Patients with AA have an increased risk of developing paroxysmal nocturnal hemoglobinuria (PNH), myelodysplastic syndrome (MDS), or acute leukemia.

Lab tests:

CBC and Automated Differential

Blood Smear with Interpretation

Liver function test

Viral hepatitis studies

LDH

Serum bilirubin

Serum B12 vitamin

Erythrocyte folate level

Fibrinogen

Bone marrow aspiration and biopsy

diepoxybutane (DEB) screening for Fanconi anemia Telomere length measurements for Dyskeratosis congenital

HLA-typing (HLA-DRB1*15)

References:

Red cell aplasia: acquired and congenital disorders

Definition:

Pure red cell aplasia (PRCA) is a rare, generally chronic condition of profound anemia characterized by a severe reduction in the number of reticulocytes in the peripheral blood and the virtual absence of erythroid precursors in the bone marrow. All other cell lineages are present and appear morphologically normal. A congenital form of red cell aplasia is known as Diamond-Blackfan anemia (DBA). DBA is associated with a number of congenital abnormalities, risk of malignancy, and marked unresponsiveness to prednisone. Acquired pure red cell aplasia (PRCA) is a rare condition of profound anemia characterized by a very low reticulocyte count and the virtual absence of erythroid precursors in the bone marrow. All other cell lines are present and seem quantitatively and morphologically normal. Many cases of acquired PRCA are idiopathic. In others, underlying conditions, such as thymoma, myelodysplastic syndromes, lymphoma, leukemia, systemic autoimmune disorders, and viral infection (ie, parvovirus B19), or treatment with drugs, such as phenytoin or chloramphenicol, are identified. PRCA has also been described in patients treated with epoetin (EPO), resulting from the induction of neutralizing antibodies directed against the EPO molecule. Most reported cases have been in patients receiving EPO for chronic kidney disease (CKD)-related anemia.

Lab tests:

CBC and Automated Differential

Blood Smear with Interpretation

Reticulocyte count

Serum bilirubin

Haptoglobin

LDH

Direct antiglobulin (Coombs)

Iron and TIBC

Bone marrow aspiration and biopsy

Liver function test

Renal function test

Antinuclear antibody

Congenital dyserythropoietic anemia

Definition:

The congenital dyserythropoietic anemias (CDAs) are a heterogeneous group of inherited blood disorders characterized by anemia and morphologic abnormalities of erythroid precursors in the bone marrow, a consequence of dyserythropoiesis and ineffective erythropoiesis. CDAs were classified into three different types: type I, type II, and type III. CDA I is inherited in an autosomal recessive pattern and it represents the second most common form of CDA. Type II CDA is the most common type of CDA that is inherited in an autosomal recessive pattern. Type III CDA is the rarest CDA variant with a familial and a sporadic form. The familia form is inherited in an autosomal dominant and the sporadic form is inherited in an autosomal recessive pattern.

Lab tests:

CBC and Automated Differential

Blood Smear with Interpretation

Reticulocyte count

Serum bilirubin

LDH

Direct antiglobulin (Coombs)

Iron and TIBC

Bone marrow aspiration and biopsy

Anemia secondary to chronic disease and systemic disorders

Definition:

The anemia of chronic disease (ACD, also called the anemia of inflammation, anemia of chronic inflammation, or hypoferremia of inflammation) was initially thought to be associated primarily with infectious, inflammatory, or neoplastic disease. However, other observations have shown that ACD can be seen in a variety of conditions, including chronic kidney disease, severe trauma, diabetes mellitus, anemia of older adults, and in those with acute or chronic immune activation. The anemia is typically normochromic, normocytic, hypoproliferative, and mild in degree.

Lab tests:

CBC and Automated Differential

Blood Smear with Interpretation

Reticulocyte count

Iron and TIBC

Bone marrow studies

CRP and ESR

Fibrinogen

Haptoglobin

Soluble transferrin receptor

sTfR – ferritin index

Anemia during pregnancy and the postpartum period

Definition:

By the second trimester of pregnancy, at least a mild degree of maternal anemia (defined as a hemoglobin concentration or hematocrit below the lower limit of normal for healthy adult females) is almost universal. Significant anemia (defined as a hemoglobin concentration <10 g/dl) occurs with a prevalence ranging between 2% and 26%, depending upon the population studied. In all populations, but particularly in the less-developed countries of the world, anemia is a major contributor to maternal and fetal morbidity and mortality.

Lab tests:

CBC and Automated Differential

Blood Smear with Interpretation

Reticulocyte count

Iron and TIBC

Serum B12 vitamin

Erythrocyte folate level

Bone marrow studies

Anemias unique to the fetus and neonate

Definition:

The reference ranges used to define normal hematocrit, hemoglobin, erythrocyte count, and the erythrocyte indices, change considerably during fetal life as well as in the weeks after birth. Consequently, the laboratory findings that define anemia in a fetus or neonate are highly dependent on the gestational and postnatal age. The most common cause of anemia in fetus and neonate is hemolytic anemia. Causes of hemolytic anemia in newborns are immune medicated (Rh and ABO incompatibility), congenital erythrocyte enzyme defects and hereditary erythrocyte membrane disorders.

Lab tests:

CBC and Automated Differential

Blood Smear with Interpretation

Reticulocyte count

Hb electrophoresis

Iron and TIBC

Coombs test (Direct and indirect antiglobulin test)

Evaluation of G6PD

Indirect and direct bilirubin level

Urinanalysis

Erythrocytosis

Definition:

Erythrocytosis is a laboratory finding in which there is an increased number of red blood cells (RBC), along with an accompanying increase in the concentration of hemoglobin in the peripheral blood. In absolute polycythemia (also called erythrocytosis) there is an increased RCM. Patients are further categorized into primary and secondary forms. Primary polycythemia is caused by an acquired or inherited mutation leading to an abnormality within RBC progenitors; it includes polycythemia vera (PV) and rare familial variants. Secondary polycythemia is caused by a circulating factor stimulating erythropoiesis, usually erythropoietin (Epo). It is most often due to an Epo response to hypoxia, but can also result from an Epo-secreting tumor.

Lab tests:

CBC and Automated Differential

Blood Smear with Interpretation

Reticulocyte count

Blood volume measurement

Serum erythropoietin

JAK2 mutation testing

Bone marrow aspiration and biopsy

References:

oung NS, Bacigalupo A, Marsh JC. Aplastic anemia: pathophysiology and treatment. Biol Blood Marrow Transplant 2010; 16:S119.
Guinan EC. Acquired aplastic anemia in childhood. Hematol Oncol Clin North Am 2009; 23:171.
Mehta, Paulette. “Wintrobe’s Clinical Hematology.” JAMA 302.22 (2009): 2488-2493.

Anemia

Anemia

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