eMedicine Specialties > Hematology > Red Blood Cells and Disorders

Hemolytic Anemia

Author: Paul Schick, MD, Emeritus Professor, Department of Internal Medicine, Thomas Jefferson University Medical College; Research Professor, Department of Internal Medicine, Drexel University College of Medicine; Adjunct Professor of Medicine, Lankenau Hospital, Wynnewood, PA
Contributor Information and Disclosures

Updated: Apr 27, 2009

Introduction

Background

Hemolysis is the premature destruction of erythrocytes, and it leads to hemolytic anemia when bone marrow activity cannot compensate for the erythrocyte loss. Clinical presentation depends on whether the onset of hemolysis is gradual or abrupt and on the severity of erythrocyte destruction. A patient with mild hemolysis may be asymptomatic. In more serious cases, the anemia can be life threatening, and patients can present with angina and cardiopulmonary decompensation. The clinical presentation also reflects the underlying cause for hemolysis. For example, sickle cell anemia is associated with a painful occlusive crisis (see Image 4 or below).

Peripheral blood smear with sickled cells at 1000...

Peripheral blood smear with sickled cells at 1000X magnification. Image courtesy of Ulrich Woermann, MD.

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Peripheral blood smear with sickled cells at 1000...

Peripheral blood smear with sickled cells at 1000X magnification. Image courtesy of Ulrich Woermann, MD.


For excellent patient education resources, visit eMedicine's Blood and Lymphatic System Center. Also, see eMedicine's patient education article Anemia.

Pathophysiology

Hemolysis is the final event triggered by a large number of hereditary and acquired disorders. The etiology of premature erythrocyte destruction is diverse and can be due to conditions such as intrinsic membrane defects, abnormal hemoglobins, erythrocyte enzymatic defects, immune destruction of erythrocytes, mechanical injury, and hypersplenism. Hemolysis is associated with a release of hemoglobin and lactic acid dehydrogenase (LDH). An increase in indirect bilirubin and urobilinogen is derived from released hemoglobin.

A patient with mild hemolysis may have normal hemoglobin levels if increased production matches the rate of erythrocyte destruction. Alternatively, patients with mild hemolysis may experience marked anemia if their bone marrow erythrocyte production is transiently shut off by viral (parvovirus B19) or other infections, resulting in uncompensated destruction of erythrocytes (aplastic hemolytic crisis, in which a decrease in the erythrocytes occurs in a patient with ongoing hemolysis). Skull and skeletal deformities can occur with a marked increase in hematopoiesis, expansion of bone in infancy, and early childhood disorders such as sickle cell anemia or thalassemia.

Polychromasia.

Polychromasia.

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Polychromasia.

Polychromasia.


Spherocytes. One arrow points to a spherocyte; th...

Spherocytes. One arrow points to a spherocyte; the other, to a normal RBC with a central pallor.

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Spherocytes. One arrow points to a spherocyte; th...

Spherocytes. One arrow points to a spherocyte; the other, to a normal RBC with a central pallor.


Frequency

International

Hemolytic anemia represents approximately 5% of all anemias.

Mortality/Morbidity

The overall incidence of death is low in cases of hemolytic anemia. However, older patients and patients with cardiovascular impairment are at an increased risk. Morbidity is dependent on the etiology of the hemolysis and the underlying disorder such as sickle cell anemia or malaria.

  • Tachycardia and dyspnea symptoms occur when the onset of hemolysis is abrupt and the anemia is severe.
  • Angina and heart failure symptoms can occur in patients with underlying cardiovascular disease and severe uncompensated hemolysis.
  • Hemosiderosis, leg ulcers, folate deficiency, and gallstones can also occur.

Race

Most of the disorders that lead to hemolysis are not specific to any race.

  • Sickle cell disorders are found primarily in Africans, African Americans, some Arabic peoples, and Aborigines in southern India.
  • Several variants of glucose-6-phosphate dehydrogenase (G6PD) deficiency exist. The A variant is generally found in West Africans and African Americans. Approximately 10% of African Americans carry at least 1 copy of the gene for this variant. The Mediterranean variant occurs in individuals of Mediterranean descent and in some Asians.

Sex

  • Most cases of hemolytic anemia are not sex specific.
  • Autoimmune hemolytic anemia (AIHA) is slightly more likely to occur in females than in males.
  • G6PD deficiency is an X-linked recessive disorder. Males are usually affected, and females are carriers.

Age

  • Hemolytic anemia can occur in persons of any age.
  • Hereditary disorders are usually evident early in life.
  • Autoimmune hemolytic anemia is more likely to occur in middle-aged and older individuals.

Clinical

History

Symptoms of hemolytic anemia are diverse and are due to the anemia, the extent of compensation, previous treatment, and the underlying disorder.

  • Patients with minimal or long-standing hemolytic anemia can be asymptomatic, so hemolysis is often found incidentally during routine laboratory testing.
  • In intravascular hemolysis, iron deficiency due to chronic hemoglobinuria can exacerbate anemia and weakness.
  • Tachycardia, dyspnea, angina, and weakness occur in patients with severe anemia. Cardiac function is sensitive to anoxia. Angina and evidence of cardiac decompensation occurs if anemia is severe or if the onset is rapid.
  • Gallstones may cause abdominal pain. Bilirubin stones can develop in patients with persistent hemolysis.
  • Bronze skin color and diabetes result from hemochromatosis due to multiple transfusions or erroneously administered iron therapy.
  • Hemoglobinuria produces dark urine. It can occur in patients with intravascular hemolysis and has similar results to a transfusion of ABO-incompatible blood.
  • Patients with thrombotic thrombocytopenic purpura (TTP) may experience fever, neurologic signs, renal failure, petechiae, and hemolysis because of the widespread occlusion of small vessels.
  • Leg ulcers may develop in patients with sickle cell anemia and other hemolytic disorders as a result of decreased red blood cell deformity and endothelial changes.
  • Penicillin, quinine, quinidine, L-dopa, and other agents may cause immune hemolysis (see Medical Care).
  • Oxidant drugs (see Diet) and stress from infections can trigger hemolysis in patients with G6PD deficiency.
  • Fava beans can induce hemolysis in susceptible individuals with the Mediterranean variant of G6PD deficiency.
  • A patient who needs a transfusion but does not show evidence of blood loss or bone marrow suppression may have hemolytic anemia.

Physical

The physical examination in an individual with hemolytic anemia can reveal signs of anemia, erythrocyte destruction, complications of hemolysis, and evidence of an underlying disease.

  • General pallor and pale conjunctivae and fingernails indicate anemia but are not specific for hemolytic anemias.
  • Tachycardia, tachypnea, and hypotension due to anoxia and decreased vascular volume usually occur in severe anemias but are not specific for hemolytic anemias.
  • Jaundice may occur because of a modest increase in indirect bilirubin in hemolysis. The rise is not specific for hemolytic disorders and may occur in liver disease, biliary obstruction, and hereditary liver disorders. Bilirubin levels are rarely greater than 4 mg/dL in hemolysis unless complicated by hepatic disease or cholelithiasis.
  • Splenomegaly
  • Leg ulcers
  • Right upper abdominal quadrant tenderness may indicate gallbladder disease.
  • Bleeding and petechiae indicate thrombocytopenia due to Evans syndrome or thrombotic thrombocytopenic purpura if neurologic signs are also present.
  • Butterfly malar rash and arthritis suggest SLE.
  • Lymphadenopathy with splenomegaly may indicate an underlying chronic CLL.

Causes

More than 200 causes for hemolysis exist. Only the main categories and some examples of hemolytic disorders are considered in this article.

  • Hereditary disorders include erythrocyte membrane and enzymatic defects and hemoglobin abnormalities. Some hereditary disorders include the following:
  • Acquired hemolytic conditions can be due to immune disorders, toxic chemicals and drugs, antiviral agents (eg, ribavirin1 ) physical damage, and infections. They can include the following:
    • Autoimmune hemolytic anemia (AIHA) may result from warm or cold autoantibody types; rarely, mixed types occur.2,3,4 Most warm autoantibodies are immunoglobulin (Ig) G and can be detected with the direct Coombs test, which is also known as the direct antiglobulin test (DAT).
    • AIHA may occur after allogeneic hematopoietic stem cell transplantation. The 3-year cumulative incidence in this population has been reported at 4.44%.5
    • Microangiopathic anemia is found in patients with disseminated intravascular coagulation (DIC) or hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura.6 Fragmented erythrocytes (schistocytes) also occur with defective prosthetic cardiac valves.
  • Autoimmune hemolytic anemia and hereditary spherocytosis are classified as examples of extravascular hemolysis because the red blood cells are destroyed in the spleen and other reticuloendothelial organs.
  • Intravascular hemolysis occurs in hemolytic anemia due to prosthetic cardiac valves, G6PD deficiency, thrombotic thrombocytopenic purpura, disseminated intravascular coagulation, and paroxysmal nocturnal hemoglobinuria (PNH).

More on Hemolytic Anemia

Overview: Hemolytic Anemia
Differential Diagnoses & Workup: Hemolytic Anemia
Treatment & Medication: Hemolytic Anemia
Follow-up: Hemolytic Anemia
Multimedia: Hemolytic Anemia
References
Further Reading
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References

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Further Reading

Related eMedicine Topics

Clinical Trials

National Guidelines Clearinghouse

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Keywords

hemolytic anemia, autoimmune hemolytic anemia, anemia, hemolysis, microangiopathic anemia, premature erythrocyte destruction, hereditary hemoglobin abnormalities, glucose-6-phosphate dehydrogenase deficiency, G6PD deficiency, G-6-PD deficiency, hereditary spherocytosis, sickle cell anemia, sickle cell trait, sickle cell disease, AIHA, disseminated intravascular coagulation, DIC, hemolytic uremic syndrome, HUS, hemolytic-uremic syndrome, TTP, thrombotic thrombocytopenic purpura, defective prosthetic cardiac valves, parvovirus B19 infection

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Contributor Information and Disclosures

Author

Paul Schick, MD, Emeritus Professor, Department of Internal Medicine, Thomas Jefferson University Medical College; Research Professor, Department of Internal Medicine, Drexel University College of Medicine; Adjunct Professor of Medicine, Lankenau Hospital, Wynnewood, PA
Paul Schick, MD is a member of the following medical societies: American College of Physicians, American Heart Association, American Society of Hematology, International Society on Thrombosis and Haemostasis, and New York Academy of Sciences
Disclosure: Nothing to disclose.

Medical Editor

Rodger L Bick, MD, PhD, FACP, Clinical Professor of Medicine, University of Texas Southwestern Medical Center; Director, Dallas and Pacific Thrombosis Hemostasis and Vascular Medicine Clinical Center
Rodger L Bick, MD, PhD, FACP is a member of the following medical societies: American Association for Cancer Research, American Association for the Advancement of Science, American Association of Blood Banks, American Cancer Society, American College of Angiology, American College of Physicians, American Geriatrics Society, American Heart Association, American Medical Association, American Society for Clinical Pathology, American Society of Hematology, Association of Clinical Scientists, California Medical Association, California Thoracic Society, International College of Angiology, International Society of Hematology, International Society on Thrombosis and Haemostasis, New York Academy of Sciences, and Southwest Oncology Group
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Ronald A Sacher, MB, BCh, MD, FRCPC, Director of the Hoxworth Blood Center, Professor, Departments of Internal Medicine and Pathology, University of Cincinnati Medical Center
Ronald A Sacher, MB, BCh, MD, FRCPC is a member of the following medical societies: American Society of Hematology
Disclosure: Glaxo Smith Kline Honoraria Speaking and teaching; Talecris Honoraria Board membership

CME Editor

Rajalaxmi McKenna, MD, FACP, Consulting Staff, Department of Medicine, Southwest Medical Consultants, SC, Good Samaritan Hospital, Advocate Health Systems
Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis
Disclosure: Nothing to disclose.

Chief Editor

Emmanuel C Besa, MD, Professor, Department of Medicine, Division of Hematologic Malignancies, Kimmel Cancer Center, Thomas Jefferson University
Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, and New York Academy of Sciences
Disclosure: Nothing to disclose.

 
 
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