Hemolytic Anemias

Hemolytic anemias, which result from premature destruction of red blood cells (RBCs), may be hereditary or acquired. Hemolytic anemias can be due to numerous causes, including RBC membrane disorders, RBC enzyme defects, immune conditions, hemoglobinopathies, and thrombotic microangiopathies, among other causes (see Classification section). Common hemolytic anemias include glucose-6-phosphate dehydrogenase (G6PD) deficiency, pyruvate kinase (PK) deficiency, and hereditary spherocytosis. Laboratory testing includes an initial evaluation for hemolysis, secondary testing to determine the etiology of hemolytic anemia, and, in some cases, molecular testing to confirm the diagnosis or determine recurrence risk.

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Clinical Overview

Quick Answers

What is the clinical presentation of hemolytic anemia?

Hemolytic anemia is a clinically heterogeneous disorder with equally heterogeneous presentations. Patients may be asymptomatic or may present with anemia and related symptoms (eg, fatigue, dyspnea, tachycardia) or hemolysis-related symptoms (jaundice, hematuria). Patients with chronic hemolysis may exhibit hepatosplenomegaly, lymphadenopathy, cholestasis, and choledocholithiasis. Additional disease-specific symptoms may occur (eg, Raynaud phenomenon in patients with cold agglutinin syndrome).

Which initial tests should be ordered in cases of suspected hemolytic anemia?

The first step in the evaluation of suspected hemolytic anemia is confirmation of hemolysis. A standard workup for hemolysis includes lactate dehydrogenase (LDH), unconjugated bilirubin, and haptoglobin tests, as well as a reticulocyte count. Hemolysis is confirmed by increases in the reticulocyte count, LDH, and unconjugated bilirubin, along with decreased haptoglobin. A peripheral smear should be ordered after hemolysis is confirmed to provide clues to the etiology of hemolytic anemia.

What can and cannot be deduced from a peripheral smear?

Although findings on a peripheral smear may suggest a particular etiology for disease (refer to Peripheral Smear section), the peripheral smear is not a standalone diagnostic test. Most findings are not specific for hemolytic anemia or particular etiologies thereof. A workup for hemolysis is recommended to confirm hemolytic anemia and inform secondary testing. In the absence of hemolysis, the use of flow cytometry tests may be considered to begin investigation of abnormal cells on the peripheral smear.

Hemolytic Anemias Testing Algorithm

Indications for Testing

Patients with unexplained anemia, particularly with reticulocytosis and/or evidence of hemolysis, should be evaluated for hemolytic anemias. Suggestive symptoms that may prompt investigation include acute jaundice and hematuria, as well as nonspecific symptoms of anemia such as dyspnea and fatigue.

Classification

The hemolytic anemias are a clinically heterogeneous group of disorders that can be classified by class or type, mechanism, and whether hemolysis is intravascular or extravascular.

Types of Hemolytic Anemia
Type	Examples	Related ARUP Consult Topics and Test Fact Sheets
RBC enzyme defects	G6PD deficiency PK deficiency Glucose phosphate isomerase deficiency Glutathione reductase deficiency Phosphoglycerate kinase deficiency Triosephosphate isomerase deficiency Adenylate kinase 1 deficiency P5N deficiency Hexokinase 1 deficiency	G6PD Deficiency Test Fact Sheet
RBC membrane defects	Hereditary spherocytosis Hereditary elliptocytosis Hereditary pyropoikilocytosis HSt PNH	Hereditary Spherocytosis Test Fact Sheet Paroxysmal Nocturnal Hemoglobinuria
Hemoglobin synthesis abnormalities	Qualitative hemoglobinopathies (eg, sickle cell disease) Thalassemias	Hemoglobinopathies Unstable Hemoglobinopathies Thalassemias
Immune, infectious causes	Cytomegalovirus Epstein-Barr virus Hepatitis C HIV Leptospira Plasmodium Mycoplasma pneumoniae Parvovirus Babesia microti	Cytomegalovirus Test Fact Sheet Epstein-Barr Virus Hepatitis C Virus Human Immunodeficiency Virus Leptospira Species - Leptospirosis Plasmodium Species - Malaria Mycoplasma pneumoniae Infection Parvovirus B19 Babesia microti - Babesiosis
Immune, autoimmune	Warm autoimmune hemolytic anemia (primary or secondary) Cold agglutinin syndrome (including cold hemagglutinin disease and paroxysmal cold hemoglobinuria) Mixed autoimmune hemolytic anemia (primary or secondary)	Cold Agglutinin Disease
Immune, microangiopathic RBC destruction	TTP HUS aHUS DIC HELLP syndrome	Thrombotic Microangiopathies Disseminated Intravascular Coagulation HELLP Syndrome
Other	Physical disruption (eg, due to mechanical valves) Envenomation (eg, from brown recluse spider venom) Systemic disease (eg, malignant hypertension) Drug induced (>150 associated drugs)
aHUS, atypical hemolytic uremic syndrome; DIC, disseminated intravascular coagulation; HELLP, hemolysis, elevated liver function tests, and low platelet count; HSt, hereditary stomatocytosis; HUS, hemolytic uremic syndrome; PNH, paroxysmal nocturnal hemoglobinuria; P5N, pyrimidine 5’-nucleotidase; TTP, thrombotic thrombocytopenic purpura

Laboratory Testing

Initial Evaluation

CBC and Workup for Hemolysis

The first step in the evaluation of hemolytic anemia is a CBC, along with a complete clinical examination and family history. If the CBC reveals normocytic or macrocytic anemia, a reticulocyte count should be performed. A standard workup for hemolysis, including lactate dehydrogenase (LDH), haptoglobin, and unconjugated bilirubin tests, is also recommended. Urinalysis may be useful, and may reveal hemoglobinuria even in the absence of visible RBCs. Urinary hemosiderin may be detected a week after onset in cases of intravascular hemolysis.

The reticulocyte count is generally increased in hemolytic anemia, which indicates the bone marrow response to hemolysis, unless there is simultaneous iron deficiency or bone marrow suppression. LDH and unconjugated bilirubin are usually elevated. Haptoglobin is most often decreased. Together, reticulocytosis, elevated LDH, elevated unconjugated bilirubin, and decreased haptoglobin confirm hemolysis.

Peripheral Smear

If not performed with the CBC, a peripheral smear with Heinz body stain should be obtained following confirmation of hemolysis. Findings noted on the peripheral smear may suggest possible diagnoses that can be determined with the appropriate secondary tests (see Secondary Testing). For a complete testing strategy based on peripheral smear morphology, see the Hemolytic Anemias Testing Algorithm.

Possible Etiologies of Hemolysis Based on Peripheral Smear Findings
Finding	Possible Etiologies
Spherocytes, elliptocytes, poikilocytes	Hereditary spherocytosis Hereditary elliptocytosis Hereditary pyropoikilocytosis Immune-mediated hemolytic anemias (eg, autoimmune hemolytic anemia, cold agglutinin disease, paroxysmal cold hemoglobinuria)
Schistocytes/fragmented cells	DIC TTP HELLP syndrome HUS aHUS Physical disruption (eg, of mechanical cardiac valve) Vasculitis Malignant hypertension
Polychromasia without other morphologic abnormality, with or without platelet decrease	PNH RBC enzyme defects
Sickle cells, target cells	Hemoglobinopathy
Stomatocytes	HSt (including dehydrated HSt, or xerocytosis; and overhydrated HSt, or hydrocytosis)
Basophilic stippling	Lead poisoning P5N deficiency
Positive Heinz body stain	Hemoglobinopathy G6PD deficiency Chemical or toxin exposure
Agglutination	Cold agglutinin disease Warm autoimmune hemolytic anemia
Unusual RBC inclusions	Infection

Direct Coombs Test

A direct Coombs test (also known as a direct antiglobulin test, or DAT) is useful to distinguish between immune and nonimmune hemolysis. The detection of immunoglobulins (IgG, IgM, or IgA) or complement (C3) in the context of hemolysis suggests immune hemolytic anemia, although the direct Coombs test is not specific. In some cases of immune hemolytic anemia, a direct Coombs test will not result in the detection of antibodies; if hemolysis cannot be otherwise explained after a negative direct Coombs test result, consider retesting with a column agglutination method, followed by secondary tests.

Secondary Testing

RBC Enzyme Defects

RBC enzymopathies are diagnosed primarily by exclusion of other potential causes of hemolysis. In patients with RBC enzymopathies, the direct Coombs test will be negative for antibodies, and the results of an osmotic fragility or cryohemolysis test will be normal.Specific abnormalities will not be observed on the peripheral smear, although nonspecific features (eg, basophilic stippling in P5N deficiency, Heinz bodies in G6PD deficiency, and poikilocytosis in PK deficiency) may be present with certain RBC enzymopathies.

To identify the specific RBC enzymopathy responsible for hemolysis, tests for reduced enzyme activity are recommended. Screening tests exist for the most common RBC enzymopathies, including G6PD and PK deficiency. For other RBC enzymopathies, activity is generally determined using a spectrophotometric assay for enzyme activity, and such assays are recommended even for the more common RBC enzymopathies. All enzyme activity assays require careful interpretation because results may be influenced by erythrocyte age, recent transfusion, the presence of leukocytes, and other factors. Molecular genetic testing is considered complementary to enzyme testing and is often required to make a definitive diagnosis of a suspected RBC enzymopathy.

RBC Membrane Defects

Suggestive findings on the peripheral smear may indicate an RBC membrane defect such as hereditary spherocytosis (indicated by spherocytes), hereditary elliptocytosis (suggested by elliptocytes), hereditary pyropoikilocytosis (suggested by poikilocytes), or HSt (indicated by stomatocytes or target cells). Additional testing may confirm or lead to a diagnosis.

Hereditary Spherocytosis

Patients with spherocytes on the peripheral smear who have a family history of hereditary spherocytosis, clinical features consistent with this disorder, an increased mean corpuscular hemoglobin concentration (MCHC), and reticulocytosis do not require any additional testing. Screening tests for hereditary spherocytosis in uncertain cases include the osmotic fragility test, acid glycerol lysis time test, osmotic gradient ektacytometry, and the eosin-5’-maleimide (EMA) binding test. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) is recommended if the clinical phenotype is more severe than would be predicted by RBC morphology or when the morphology is more severe than would be expected from studies in an affected family member. If there is ambiguity in the diagnosis, SDS-PAGE is recommended before proceeding with splenectomy. Although not generally required in cases of hereditary spherocytosis, molecular genetic testing may be useful if clinical suspicion persists despite negative test results.

Hereditary Elliptocytosis

Secondary testing for hereditary elliptocytosis is recommended if there is no family history and if there are only a few elliptocytes visible on the peripheral smear. A diagnosis of hereditary elliptocytosis can be confirmed via SDS-PAGE for protein 4.1 and spectrin analysis, ektacytometry, or laser-assisted optical rotational cell analyzer (LORCA). Molecular genetic testing may also be useful.

Hereditary Stomatocytosis

There are several different subtypes of HSt, including dehydrated HSt (also known as xerocytosis), overhydrated HSt (also known as hydrocytosis), cryohydrocytosis (CHC), and familial pseudohyperkalemia (FP). Obtaining an accurate diagnosis is particularly important in HSt because treatment differs for different subtypes of the disease. Ion flux measurement, ektacytometry, LORCA, or molecular genetic testing can be used to diagnose HSt and identify the subtype.

Hereditary Pyropoikilocytosis

A mean corpuscular volume (MCV) of 50-60 fL or a greatly reduced mean cell fluorescence (MCF) as detected by EMA support a diagnosis of hereditary pyropoikilocytosis. The diagnosis can be confirmed via spectrin analysis, ektacytometry, LORCA, or molecular genetic testing.

Autoimmune Hemolytic Anemias

Because autoimmune hemolytic anemia may arise from a number of causes, including recent transfusion, infections, other autoimmune conditions, drugs, and lymphoproliferative malignancies, careful consideration of the clinical picture is required.

Autoimmune hemolytic anemia is suggested by a positive result (in the absence of another explanation) on the direct Coombs test. However, a negative result does not rule out an autoimmune cause of hemolysis. The specific antibodies detected by the direct Coombs test may point to a particular etiology of hemolytic anemia (eg, a positive IgG without positive C3 suggests warm autoimmune hemolytic anemia). A positive direct Coombs test may also point to additional testing (eg, a positive C3 may warrant a cold agglutinins test for cold agglutinin disease or, in the applicable clinical circumstances, a Donath Landsteiner test for paroxysmal cold hemoglobinuria).

Microangiopathic RBC Destruction

Microangiopathic RBC destruction occurs due to RBC fragmentation and is suggested by the presence of schistocytes on the peripheral smear. A number of conditions may lead to microangiopathic RBC destruction.

Conditions with Microangiopathic RBC Destruction
Cause of RBC Fragmentation	Detailed Laboratory Testing Information
Thrombotic thrombocytic purpura	Thrombotic Microangiopathies
Hemolytic uremic syndrome
Atypical hemolytic uremic syndrome
Disseminated intravascular coagulation	Disseminated Intravascular Coagulation
Hemolysis, elevated liver function tests, and low platelet count constellation (HELLP syndrome)	HELLP Syndrome

Hemoglobinopathies and Thalassemias

For more information on secondary testing for hemoglobinopathies, including unstable hemoglobinopathies and thalassemias, see the Hemoglobinopathies, Unstable Hemoglobinopathies, and Thalassemias ARUP Consult topics and the Hemoglobinopathies Testing Algorithm.

Other Causes of Hemolytic Anemia

The clinical history, initial evaluation, and peripheral smear may suggest another cause for hemolytic anemia (eg, abnormal inclusions on the peripheral smear in cases of infection). Selecting the appropriate laboratory tests requires careful clinical judgment. See the Hemolytic Anemias Testing Algorithm for a suggested testing strategy based on peripheral smear and clinical findings.

Molecular Genetic Testing

Genetic testing can be performed to confirm a diagnosis, determine a diagnosis, or assess recurrence risk for a hereditary hemolytic anemia. Panel testing may be useful to distinguish between disorders with overlapping clinical presentations. Genes tested, clinical sensitivity, costs, and methodology vary between panels; clinical judgment is required to select the appropriate panel test. Familial variant testing may be useful to confirm or rule out a diagnosis in at-risk family members if a known familial variant exists. More comprehensive testing (eg, whole exome sequencing) may also be useful in certain circumstances.

Genes Involved in Hereditary Hemolytic Anemias
Condition	Genes	Inheritance
Hereditary RBC Enzyme Defects
G6PD deficiency	G6PD	XR
PK deficiency	PKLR	AR
Glucose phosphate isomerase deficiency	GP1	AR
Glutathione reductase deficiency	GSR	AR
Phosphoglycerate kinase deficiency	PGK1	XL
Triosephosphate isomerase deficiency	TPI1	AR
Adenylate kinase 1	AK1	AR
P5N	NT5C3	AR
Hexokinase 1	HK1	AR
Phosphofructokinase deficiency (glycogen storage disease VII, Tauri disease)	PFKM	AR
Hereditary RBC Membrane Defects
Condition	Genes	Inheritance
Hereditary spherocytosis	ANK1, SLC4A1, SPTB, EPB42	AD/AR
Hereditary elliptocytosis/pyropoikilocytosis	SPTA1, SPTB, EPB41	AD/AR
HSt	PIEZO1, KCNN4	AD
AD, autosomal dominant; AR, autosomal recessive; XL, X-linked; XR, X-linked recessive

Testing in Neonates

Autoimmune Hemolytic Anemias

If a mother has a positive direct Coombs result during pregnancy, or if autoimmune hemolytic anemia is diagnosed, cord blood should be tested with a direct Coombs test following delivery. If jaundice is observed, or if the direct Coombs tests is positive, a CBC, reticulocyte count, and bilirubin test are recommended. Monitoring for anemia and hyperbilirubinemia is recommended.

ARUP Lab Tests

Evaluate for hemolysis, thrombocytopenia, and leukopenia

CBC with Platelet Count and Automated Differential 0040003

Method: Automated Cell Count/Differential

Assess bone marrow response to anemia

Reticulocytes, Percent and Number 0040022

Method: Flow Cytometry

Assess hemolysis

Lactate Dehydrogenase, Serum or Plasma 0020006

Method: Quantitative Enzymatic

Bilirubin, Total, Serum or Plasma 0020032

Method: Spectrophotometry

Haptoglobin 0050280

Method: Quantitative Immunoturbidimetry

Evaluate cellular morphology

Blood Smear with Interpretation 3001947

Method: Cytochemical Stain

Use as a nonspecific screen for hemolysis due to drugs/toxins, enzyme deficiencies, thalassemias, and unstable hemoglobins

Heinz Body Stain 0049090

Method: Supravital Stain

Detect in vivo coating of RBCs with immunoglobulin and complement degradation products on the patient's RBCs

Useful for antibody identification and evaluation of transfusion reactions, hemolytic disease of the fetus and newborn (HDFN), and autoimmune hemolytic anemia associated with disease and/or drugs

Direct Coombs (Anti-Human Globulin) 0013008

Method: Hemagglutination

May be detected a week after onset in cases of intravascular hemolysis

Hemosiderin, Urine 0020222

Method: Semi-Quantitative Microscopy

RBC Membrane Defects

Functional testing of RBC sensitivity to osmotic stress

Do not use to distinguish between spherocytes in hereditary spherocytosis and acquired autoimmune hemolytic anemia

Osmotic Fragility, Erythrocyte 2002257

Method: Spectrophotometry

Preferred initial screening test for G6PD deficiency

Glucose-6-Phosphate Dehydrogenase 0080135

Method: Quantitative Enzymatic

Preferred initial screening test for PK deficiency

Pyruvate Kinase 0080290

Method: Quantitative Enzymatic

RBC Membrane Defects

Functional testing of RBC sensitivity to osmotic stress

Do not use to distinguish between spherocytes in hereditary spherocytosis and acquired autoimmune hemolytic anemia

Osmotic Fragility, Erythrocyte 2002257

Method: Spectrophotometry

Confirm diagnosis of hereditary spherocytosis when hemolytic anemia and spherocytes are present

RBC Band 3 Protein Reduction in Hereditary Spherocytosis 2008460

Method: Qualitative Flow Cytometry

Autoimmune Hemolytic Anemias

Determine if Donath-Landsteiner antibodies are present

Diagnose paroxysmal cold hemoglobinuria

Donath Landsteiner 0013039

Method: Hemolysis

Identify antibodies as cause of hemolysis

Cold Agglutinins 0050175

Method: Semi-Quantitative Hemagglutination

Molecular Genetic Testing

Determine etiology, elicit inheritance pattern, and assess recurrence risk in individuals with unexplained hemolytic anemia, unexplained hyperbilirubinemia, family history of unexplained hemolytic anemia, or pregnancy with hydrops fetalis of unknown etiology

Hereditary Hemolytic Anemia Panel Sequencing 2012052

Method: Massively Parallel Sequencing

Preferred genetic test for individuals of African descent

Glucose-6-Phosphate Dehydrogenase (G6PD) 2 Mutations 0051684

Method: Polymerase Chain Reaction/ TaqMAN

Preferred test for individuals of high-risk ethnic backgrounds other than those of African descent

Appropriate test for symptomatic individuals of African descent who do not carry the A- allele

For initial screening for GP6D deficiency, refer to glucose-6-phosphate dehydrogenase

Glucose-6-Phosphate Dehydrogenase Deficiency (G6PD) Sequencing 2007163

Method: Polymerase Chain Reaction/Sequencing

Confirm PK deficiency in individuals with abnormal PK enzyme activity and/or clinical findings

Assess carrier status for PK deficiency

Pyruvate Kinase Deficiency (PKLR) Sequencing 3002059

Method: Polymerase Chain Reaction/Sequencing

Test for a known familial sequence variant previously identified in a family member

Familial Mutation, Targeted Sequencing 2001961

Method: Polymerase Chain Reaction/Sequencing

Test Fact Sheet(s)

Hereditary Hemolytic Anemia Panel, Sequencing

Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency

Medical Experts

Agarwal, Archana Mishra, MD, Medical Director, Hematopathology and Special Genetics, at ARUP Laboratories; Associate Professor of Clinical Pathology, University of Utah

References

Phillips J, Henderson AC. Hemolytic Anemia: Evaluation and Differential Diagnosis. Am Fam Physician. 2018; 98(6): 354-361. PubMed
Hill QA, Stamps R, Massey E, Grainger JD, Provan D, Hill A, British Society for Haematology. The diagnosis and management of primary autoimmune haemolytic anaemia. Br J Haematol. 2017; 176(3): 395-411. PubMed
Koralkova P, van Solinge WW, van Wijk R. Rare hereditary red blood cell enzymopathies associated with hemolytic anemia - pathophysiology, clinical aspects, and laboratory diagnosis. Int J Lab Hematol. 2014; 36(3): 388-97. PubMed
Gallagher PG. Diagnosis and management of rare congenital nonimmune hemolytic disease. Hematology Am Soc Hematol Educ Program. 2015; 2015: 392-9. PubMed
King M, Garçon L, Hoyer JD, Iolascon A, Picard V, Stewart G, Bianchi P, Lee S, Zanella A, International Council for Standardization in Haematology. ICSH guidelines for the laboratory diagnosis of nonimmune hereditary red cell membrane disorders. Int J Lab Hematol. 2015; 37(3): 304-25. PubMed
Bolton-Maggs PH, Stevens RF, Dodd NJ, Lamont G, Tittensor P, King M, General Haematology Task Force of the British Committee for Standards in Haematology. Guidelines for the diagnosis and management of hereditary spherocytosis. Br J Haematol. 2004; 126(4): 455-74. PubMed

Additional Resources

Barcellini W. Immune Hemolysis: Diagnosis and Treatment Recommendations. Semin Hematol. 2015; 52(4): 304-12. PubMed

Bass GF, Tuscano ET, Tuscano JM. Diagnosis and classification of autoimmune hemolytic anemia. Autoimmun Rev. 2014; 13(4-5): 560-4. PubMed

Cappellini MD, Fiorelli G. Glucose-6-phosphate dehydrogenase deficiency. Lancet. 2008; 371(9606): 64-74. PubMed

Grace RF, Zanella A, Neufeld EJ, Morton H, Eber S, Yaish H, Glader B. Erythrocyte pyruvate kinase deficiency: 2015 status report. Am J Hematol. 2015; 90(9): 825-30. PubMed

Höchsmann B, Schrezenmeier H. Congenital CD59 Deficiency. Hematol Oncol Clin North Am. 2015; 29(3): 495-507. PubMed

Michel M. Classification and therapeutic approaches in autoimmune hemolytic anemia: an update. Expert Rev Hematol. 2011; 4(6): 607-18. PubMed

Naik R. Warm autoimmune hemolytic anemia. Hematol Oncol Clin North Am. 2015; 29(3): 445-53. PubMed

Shanbhag S, Spivak J. Paroxysmal cold hemoglobinuria. Hematol Oncol Clin North Am. 2015; 29(3): 473-8. PubMed

Zantek ND, Koepsell SA, Tharp DR, Cohn CS. The direct antiglobulin test: a critical step in the evaluation of hemolysis. Am J Hematol. 2012; 87(7): 707-9. PubMed

Resources from the ARUP Institute for Clinical and Experimental Pathology®

Agarwal AM, Nussenzveig RH, Reading NS, Patel JL, Sangle N, Salama ME, Prchal JT, Perkins SL, Yaish HM, Christensen RD. Clinical utility of next-generation sequencing in the diagnosis of hereditary haemolytic anaemias. Br J Haematol. 2016; PubMed

Christensen RD, Agarwal AM, Nussenzveig RH, Heikal N, Liew MA, Yaish HM. Evaluating eosin-5-maleimide binding as a diagnostic test for hereditary spherocytosis in newborn infants. J Perinatol. 2015; 35(5): 357-61. PubMed

Christensen RD, Yaish HM, Nussenzveig RH, Agarwal AM. Siblings with severe pyruvate kinase deficiency and a complex genotype. Am J Med Genet A. 2016; 170(9): 2449-52. PubMed

Christensen RD, Yaish HM, Nussenzveig RH, Reading S, Agarwal AM, Eggert LD, Prchal JT. Acute kernicterus in a neonate with O/B blood group incompatibility and a mutation in SLC4A1. Pediatrics. 2013; 132(2): e531-4. PubMed

Reading S, Ruiz-Bonilla JA, Christensen RD, Cáceres-Perkins W, Prchal JT. A patient with both methemoglobinemia and G6PD deficiency: A therapeutic conundrum. Am J Hematol. 2017; 92(5): 474-477. PubMed

Reading S, Sirdah MM, Shubair ME, Nelson BE, Al-Kahlout MS, Al-Tayeb JM, Aboud LN, Shaban MA, Luzzatto L, Prchal JT. Favism, the commonest form of severe hemolytic anemia in Palestinian children, varies in severity with three different variants of G6PD deficiency within the same community. Blood Cells Mol Dis. 2016; 60: 58-64. PubMed

Sirdah M, Reading S, Perkins SL, Shubair M, Aboud L, Prchal JT. Hemolysis and Mediterranean G6PD mutation (c.563 C>T) and c.1311 C>T polymorphism among Palestinians at Gaza Strip. Blood Cells Mol Dis. 2012; 48(4): 203-8. PubMed

Sirdah M, Reading S, Vankayalapati H, Perkins SL, Shubair ME, Aboud L, Roper D, Prchal JT. Molecular heterogeneity of glucose-6-phosphate dehydrogenase deficiency in Gaza Strip Palestinians. Blood Cells Mol Dis. 2012; 49(3-4): 152-8. PubMed

Sirdah MM, Shubair ME, Al-Kahlout MS, Al-Tayeb JM, Prchal JT, Reading S. Possible association of 3' UTR +357 A>G, IVS11-nt 93 T>C, c.1311 C>T polymorphism with G6PD deficiency. Hematology. 2017; 22(6): 370-374. PubMed

Swierczek S, Agarwal AM, Naidoo K, Lorenzo FR, Whisenant J, Nussenzveig RH, Agarwal N, Coetzer TL, Prchal JT. Novel exon 2 α spectrin mutation and intragenic crossover: three morphological phenotypes associated with four distinct α spectrin defects. Haematologica. 2013; 98(12): 1972-9. PubMed

Testing Algorithms

Hemolytic Anemias Testing Algorithm

Read more about Hemolytic Anemias Testing Algorithm

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November 2019

Last Update: November 2019

Hemolytic Anemias

Quick Answers

What is the clinical presentation of hemolytic anemia?

Which initial tests should be ordered in cases of suspected hemolytic anemia?

What can and cannot be deduced from a peripheral smear?

Hemolytic Anemias Testing Algorithm

Indications for Testing

Classification

Laboratory Testing

Initial Evaluation

CBC and Workup for Hemolysis

Peripheral Smear

Direct Coombs Test

Secondary Testing

RBC Enzyme Defects

RBC Membrane Defects

Hereditary Spherocytosis

Hereditary Elliptocytosis

Hereditary Stomatocytosis

Hereditary Pyropoikilocytosis

Autoimmune Hemolytic Anemias

Microangiopathic RBC Destruction

Hemoglobinopathies and Thalassemias

Other Causes of Hemolytic Anemia

Molecular Genetic Testing

Testing in Neonates

ARUP Lab Tests

Initial Evaluation

Secondary Evaluation

Test Fact Sheet(s)

Medical Experts

References

Additional Resources

Resources from the ARUP Institute for Clinical and Experimental Pathology®

Hemolytic Anemias Testing Algorithm

ARUP Laboratories

ARUP Websites

ARUP Consult


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Hemolytic Anemias

Quick Answers

What is the clinical presentation of hemolytic anemia?

Which initial tests should be ordered in cases of suspected hemolytic anemia?

What can and cannot be deduced from a peripheral smear?

Hemolytic Anemias Testing Algorithm

Indications for Testing

Classification

Laboratory Testing

Initial Evaluation

CBC and Workup for Hemolysis

Peripheral Smear

Direct Coombs Test

Secondary Testing

RBC Enzyme Defects

RBC Membrane Defects

Hereditary Spherocytosis

Hereditary Elliptocytosis

Hereditary Stomatocytosis

Hereditary Pyropoikilocytosis

Autoimmune Hemolytic Anemias​

Microangiopathic RBC Destruction

Hemoglobinopathies and Thalassemias​

Other Causes of Hemolytic Anemia

Molecular Genetic Testing

Testing in Neonates

ARUP Lab Tests

Initial Evaluation

Secondary Evaluation

Test Fact Sheet(s)

Medical Experts

References

Additional Resources

Resources from the ARUP Institute for Clinical and Experimental Pathology®

Hemolytic Anemias Testing Algorithm

ARUP Laboratories

ARUP Websites

ARUP Consult

Autoimmune Hemolytic Anemias

Hemoglobinopathies and Thalassemias