Diagnosis of hemolytic anemia in the adult
- Stanley L Schrier, MD
Stanley L Schrier, MD
- Editor-in-Chief — Hematology
- Section Editor — Myeloproliferative Disorders; Red Blood Cell Disorders
- Professor of Medicine
- Stanford University School of Medicine
Hemolytic anemia is defined as anemia due to a shortened survival of circulating red blood cells (RBCs) due to their premature destruction. There are numerous causes of hemolytic anemia, including inherited and acquired conditions, acute and chronic processes, and mild to potentially life-threatening severity. Occasionally the cause will be obvious from the history, physical examination, or findings on the peripheral blood smear, but often the ultimate diagnosis requires a synthesis of all of this information and additional laboratory testing.
The key finding that suggests hemolytic anemia is an increase in the reticulocyte count that is not explained by recent bleeding or recent correction of iron deficiency or other nutrient deficiency. Patients may also have evidence of RBC destruction including increased lactate dehydrogenase (LDH) and bilirubin, decreased haptoglobin, and spherocytes on the peripheral blood smear.
The causes of hemolytic anemia and a diagnostic approach to the adult with unexplained hemolytic anemia are discussed here. Other topic reviews present general approaches to determining the cause of anemia and diagnosis of specific types of hemolytic anemia:
●General approach, child – (See "Approach to the child with anemia".)
●General approach, adult – (See "Approach to the adult patient with anemia".)To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- van Wijk R, van Solinge WW. The energy-less red blood cell is lost: erythrocyte enzyme abnormalities of glycolysis. Blood 2005; 106:4034.
- Poyart C, Wajcman H. Hemolytic anemias due to hemoglobinopathies. Mol Aspects Med 1996; 17:129.
- Jacobasch G, Rapoport SM. Hemolytic anemias due to erythrocyte enzyme deficiencies. Mol Aspects Med 1996; 17:143.
- Bossi D, Russo M. Hemolytic anemias due to disorders of red cell membrane skeleton. Mol Aspects Med 1996; 17:171.
- Walshe JM. The acute haemolytic syndrome in Wilson's disease--a review of 22 patients. QJM 2013; 106:1003.
- Kummerfeldt CE, Toma A, Badheka AO, et al. Severe hemolytic anemia and acute kidney injury after percutaneous continuous-flow ventricular assistance. Circ Heart Fail 2011; 4:e20.
- Qian Q, Nath KA, Wu Y, et al. Hemolysis and acute kidney failure. Am J Kidney Dis 2010; 56:780.
- Pimstone NR. Renal degradation of hemoglobin. Semin Hematol 1972; 9:31.
- Pollycove M. Iron metabolism and kinetics. Semin Hematol 1966; 3:235.
- Berlin NI, Berk PD. Quantitative aspects of bilirubin metabolism for hematologists. Blood 1981; 57:983.
- Coburn RF, Williams WJ, White P, Kahn SB. The production of carbon monoxide from hemoglobin in vivo. J Clin Invest 1967; 46:346.
- Landaw SA. Homeostasis, survival and red cell kinetics: Measurement and imaging of red cell production. In: Hematology. Basic Principles and Practice, 2nd ed, Hoffman R, Benz EJ, Shattil SJ (Eds), Churchill Livingstone, New York 1995. p.448.
- Liesveld JL, Rowe JM, Lichtman MA. Variability of the erythropoietic response in autoimmune hemolytic anemia: analysis of 109 cases. Blood 1987; 69:820.
- Erslev AJ. Reticulocyte enumeration. In: Williams' Hematology, 5th ed, Beutler E, Lichtman MA, Coller BS, et al. (Eds), McGraw-Hill, New York 1995. p.L28.
- Red blood cell diseases: Red cell production, red cell indices, and the reticulocyte count. In: Hematology. A Pathophysiological Approach, Babior BM, Stossel TP (Eds), Churchill Livingstone, New York 1984. p.13.
- Marchand A, Galen RS, Van Lente F. The predictive value of serum haptoglobin in hemolytic disease. JAMA 1980; 243:1909.
- Stahl WM. Acute phase protein response to tissue injury. Crit Care Med 1987; 15:545.
- Galen RS. Application of the predictive value model in the analysis of test effectiveness. Clin Lab Med 1982; 2:685.
- Conley CL, Lippman SM, Ness P. Autoimmune hemolytic anemia with reticulocytopenia. A medical emergency. JAMA 1980; 244:1688.
- Serjeant GR, Serjeant BE, Thomas PW, et al. Human parvovirus infection in homozygous sickle cell disease. Lancet 1993; 341:1237.
- Saarinen UM, Chorba TL, Tattersall P, et al. Human parvovirus B19-induced epidemic acute red cell aplasia in patients with hereditary hemolytic anemia. Blood 1986; 67:1411.
- Diehl LF, Ketchum LH. Autoimmune disease and chronic lymphocytic leukemia: autoimmune hemolytic anemia, pure red cell aplasia, and autoimmune thrombocytopenia. Semin Oncol 1998; 25:80.
- L'Acqua C, Hod E. New perspectives on the thrombotic complications of haemolysis. Br J Haematol 2015; 168:175.
- RBC TURNOVER IN HEMOLYTIC ANEMIA
- CONCEPTUAL FRAMEWORK
- Intracorpuscular versus extracorpuscular defects
- - Intracorpuscular defects
- - Extracorpuscular defects
- Immune versus non-immune
- Site of RBC destruction
- - Intravascular hemolysis
- - Extravascular hemolysis
- LIST OF CAUSES
- DIAGNOSTIC APPROACH
- Overview of the evaluation
- History and physical examination
- Laboratory confirmation of hemolysis
- - CBC/blood smear review
- - High reticulocyte count
- - High LDH and bilirubin; low haptoglobin
- Immediate management issues before the cause is identified
- Testing to determine the cause of hemolysis
- ATYPICAL PRESENTATIONS
- Hemolysis without reticulocytosis
- Hemolysis without anemia
- Reticulocytosis without hemolysis
- THROMBOTIC COMPLICATIONS
- SOCIETY GUIDELINE LINKS
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS