Hemolytic anemia

Hemolytic anemia is a form of anemia due to hemolysis, the abnormal breakdown of red blood cells (RBCs), either in the blood vessels (intravascular hemolysis) or elsewhere in the human body (extravascular, but usually in the spleen). It has numerous possible consequences, ranging from relatively harmless to life-threatening. The general classification of hemolytic anemia is either inherited or acquired. Treatment depends on the cause and nature of the breakdown.

Hemolytic anemia
Other namesHaemolytic anaemia

Symptoms of hemolytic anemia are similar to other forms of anemia (fatigue and shortness of breath), but in addition, the breakdown of red cells leads to jaundice and increases the risk of particular long-term complications, such as gallstones[1] and pulmonary hypertension.[2]

Signs and symptoms

In general, signs of anemia (pallor, fatigue, shortness of breath, and potential for heart failure) are present. In small children, failure to thrive may occur in any form of anemia.[3][4] Certain aspects of the medical history can suggest a cause for hemolysis, such as drugs, consumption of fava beans due to Favism, the presence of prosthetic heart valve, or other medical illness.

Chronic hemolysis leads to an increased excretion of bilirubin into the biliary tract, which in turn may lead to gallstones.[1] The continuous release of free hemoglobin has been linked with the development of pulmonary hypertension (increased pressure over the pulmonary artery);[2] this, in turn, leads to episodes of syncope (fainting), chest pain, and progressive breathlessness. Pulmonary hypertension eventually causes right ventricular heart failure, the symptoms of which are peripheral edema (fluid accumulation in the skin of the legs) and ascites (fluid accumulation in the abdominal cavity).


They may be classified according to the means of hemolysis, being either intrinsic in cases where the cause is related to the red blood cell (RBC) itself, or extrinsic in cases where factors external to the RBC dominate.[5] Intrinsic effects may include problems with RBC proteins or oxidative stress handling, whereas external factors include immune attack and microvascular angiopathies (RBCs are mechanically damaged in circulation).

Intrinsic causes

Hereditary (inherited) hemolytic anemia can be due to :

Extrinsic causes

Acquired hemolytic anemia may be caused by immune-mediated causes, drugs and other miscellaneous causes.

Site of RBC destruction


Hemolytic anemia involves the following:

  1. Abnormal and accelerated destruction of red cells and, in some anemias, their precursors
  2. Increased breakdown of hemoglobin, which may result in:
    1. increased bilirubin level (mainly indirect-reacting) with jaundice
    2. increased fecal and urinary urobilinogen
    3. Hemoglobinemia, methemalbuminemia, hemoglobinuria and hemosiderinuria (where there is significant intravascular hemolysis).
  3. Bone marrow compensatory reaction:
    1. Erythroid hyperplasia with accelerated production of red cells, reflected by reticulocytosis, and slight macrocytosis in peripheral blood
    2. Expansion of bone marrow in infants and children with severe chronic hemolysis – changes in bone configuration visible on X-ray
  4. The balance between red cell destruction and marrow compensation determines the severity of anemias.

In a healthy person, a red blood cell survives 90 to 120 days in the circulation, so about 1% of human red blood cells break down each day. The spleen (part of the reticulo-endothelial system) is the main organ that removes old and damaged RBCs from the circulation. In healthy individuals, the breakdown and removal of RBCs from the circulation is matched by the production of new RBCs in the bone marrow.

In conditions where the rate of RBC breakdown is increased, the body initially compensates by producing more RBCs; however, breakdown of RBCs can exceed the rate that the body can make RBCs, and so anemia can develop. Bilirubin, a breakdown product of hemoglobin, can accumulate in the blood, causing jaundice.

In general, hemolytic anemia occurs as a modification of the RBC life cycle. That is, instead of being collected at the end of its useful life and disposed of normally, the RBC disintegrates in a manner allowing free iron-containing molecules to reach the blood. With their complete lack of mitochondria, RBCs rely on glycolysis for the materials needed to reduce oxidative damage. Any limitations of glycolysis can result in more susceptibility to oxidative damage and a short or abnormal lifecycle. If the cell is unable to signal to the reticuloendothelial phagocytes by externalizing phosphatidylserine, it is likely to lyse through uncontrolled means.[9][10][11]

The distinguishing feature of intravascular hemolysis is the release of RBC contents into the blood stream. The metabolism and elimination of these products, largely iron-containing compounds capable of doing damage through Fenton reactions, is an important part of the condition. Several reference texts exist on the elimination pathways, for example.[12][13][14] Free hemoglobin can bind to haptoglobin, and the complex is cleared from the circulation; thus, a decrease in haptoglobin can support a diagnosis of hemolytic anemia. Alternatively, hemoglobin may oxidize and release the heme group that is able to bind to either albumin or hemopexin. The heme is ultimately converted to bilirubin and removed in stool and urine.[12] Hemoglobin may be cleared directly by the kidneys resulting in fast clearance of free hemoglobin but causing the continued loss of hemosiderin loaded renal tubular cells for many days.

Additional effects of free hemoglobin seem to be due to specific reactions with NO.[15]


The diagnosis of hemolytic anemia can be suspected on the basis of a constellation of symptoms and is largely based on the presence of anemia, an increased proportion of immature red cells (reticulocytes) and a decrease in the level of haptoglobin, a protein that binds free hemoglobin. Examination of a peripheral blood smear and some other laboratory studies can contribute to the diagnosis. Symptoms of hemolytic anemia include those that can occur in all anemias as well as the specific consequences of hemolysis. All anemias can cause fatigue, shortness of breath, decreased ability to exercise when severe. Symptoms specifically related to hemolysis include jaundice and dark colored urine due to the presence of hemoglobin (hemoglobinuria). When restricted to the morning hemoglobinuria may suggest paroxysmal nocturnal haemoglobinuria. Direct examination of blood under a microscope in a peripheral blood smear may demonstrate red blood cell fragments called schistocytes, red blood cells that look like spheres (spherocytes), and/or red blood cells missing small pieces (bite cells). An increased number of newly made red blood cells (reticulocytes) may also be a sign of bone marrow compensation for anemia. Laboratory studies commonly used to investigate hemolytic anemia include blood tests for breakdown products of red blood cells, bilirubin and lactate dehydrogenase, a test for the free hemoglobin binding protein haptoglobin, and the direct Coombs test to evaluate antibody binding to red blood cells suggesting autoimmune hemolytic anemia.


Definitive therapy depends on the cause:

  • Symptomatic treatment can be given by blood transfusion, if there is marked anemia. A positive Coombs test is a relative contraindication to transfuse the patient. In cold hemolytic anemia there is advantage in transfusing warmed blood.
  • In severe immune-related hemolytic anemia, steroid therapy is sometimes necessary.
  • In steroid resistant cases, consideration can be given to rituximab or addition of an immunosuppressant (azathioprine, cyclophosphamide).
  • Association of methylprednisolone and intravenous immunoglobulin can control hemolysis in acute severe cases.
  • Sometimes splenectomy can be helpful where extravascular hemolysis, or hereditary spherocytosis, is predominant (i.e., most of the red blood cells are being removed by the spleen).[16]

Other animals

Hemolytic anemia affects nonhuman species as well as humans. It has been found, in a number of animal species, to result from specific triggers.[17]

Some notable cases include hemolytic anemia found in black rhinos kept in captivity, with the disease, in one instance, affecting 20% of captive rhinos at a specific facility.[18][19][20] The disease is also found in wild rhinos.[21]

Dogs and cats differ slightly from humans in some details of their RBC composition and have altered susceptibility to damage, notably, increased susceptibility to oxidative damage from consumption of onion. Garlic is less toxic to dogs than onion.[22]


  1. Trotman, BW (1991). "Pigment gallstone disease". Gastroenterology clinics of North America. 20 (1): 111–26. ISSN 0889-8553. PMID 2022417.
  2. Machado, Roberto F.; Gladwin, Mark T. (2010). "Pulmonary Hypertension in Hemolytic Disorders". Chest. Elsevier BV. 137 (6): 30S–38S. doi:10.1378/chest.09-3057. ISSN 0012-3692. PMC 2882115. PMID 20522578.
  3. Kahre, Tiina; Teder, Maris; Panov, Maarja; Metspalu, Andres (2004). "Severe CF manifestation with anaemia and failure to thrive in a 394delTT homozygous patient". Journal of Cystic Fibrosis. Elsevier BV. 3 (1): 58–60. doi:10.1016/j.jcf.2003.12.009. ISSN 1569-1993.
  4. Hypoproteinemia, Anemia, and Failure to Thrive in an Infant
  5. Current Medical Diagnosis and Treatment 2009 By Stephen J. McPhee, Maxine A. Papadakis page 436 https://books.google.com/books?id=zQlH4mXSziYC&pg=PT454&dq=hemoglobin+hemosiderin+hemolysis+bilirubin&ei=Z2P_SuzwA6D2ygT9vOz3Dg#v=onepage&q=hemoglobin%20hemosiderin%20hemolysis%20bilirubin&f=false
  6. Telford RD, Sly GJ, Hahn AG, Cunningham RB, Bryant C, Smith JA (January 2003). "Footstrike is the major cause of hemolysis during running". J. Appl. Physiol. 94 (1): 38–42. doi:10.1152/japplphysiol.00631.2001. PMID 12391035.
  7. Lippi G, Schena F, Salvagno GL, Aloe R, Banfi G, Guidi GC (July 2012). "Foot-strike haemolysis after a 60-km ultramarathon". Blood Transfus. 10 (3): 377–383. doi:10.2450/2012.0167-11. PMC 3417738. PMID 22682343.
  8. Wise, Donald Lee (2000). Biomaterials Engineering and Devices: Orthopedic, dental, and bone graft applications. ISBN 978-0-89603-859-2.
  9. Kolb S, Vranckx R, Huisse MG, Michel JB, Meilhac O (July 2007). "The phosphatidylserine receptor mediates phagocytosis by vascular smooth muscle cells". The Journal of Pathology. 212 (3): 249–59. doi:10.1002/path.2190. PMID 17534843.
  10. Bosman GJ, Willekens FL, Werre JM (2005). "Erythrocyte aging: a more than superficial resemblance to apoptosis?" (PDF). Cellular Physiology and Biochemistry. 16 (1–3): 1–8. doi:10.1159/000087725. PMID 16121027.
  11. Bratosin D, Mazurier J, Tissier JP, et al. (February 1998). "Cellular and molecular mechanisms of senescent erythrocyte phagocytosis by macrophages. A review". Biochimie. 80 (2): 173–95. doi:10.1016/S0300-9084(98)80024-2. PMID 9587675.
  12. Hematology in clinical practice: a guide to diagnosis and management By Robert S. Hillman, Kenneth A. Ault, Henry M. Rinder page 136-139 https://books.google.com/books?id=NJs1VpA8SEoC&pg=PA138&dq=hemoglobin+hemosiderin+hemolysis+bilirubin&ei=Z2P_SuzwA6D2ygT9vOz3Dg#v=onepage&q=hemoglobin%20hemosiderin%20hemolysis%20bilirubin&f=false
  13. Wintrobe's Clinical Hematology, Volume 1 By John P. Greer https://books.google.com/books?id=68enzUD7BVgC&pg=PA161&dq=hemoglobin+hemosiderin+hemolysis+bilirubin&ei=Z2P_SuzwA6D2ygT9vOz3Dg#v=onepage&q=hemoglobin%20hemosiderin%20hemolysis%20bilirubin&f=false page 160
  14. Bradencarter (21 January 2017). "What is Hemolytic Anemia?". hemolyticanemia.org. Retrieved 21 January 2017.
  15. Boretti FS, Buehler PW, D'Agnillo F, et al. (August 2009). "Sequestration of extracellular hemoglobin within a haptoglobin complex decreases its hypertensive and oxidative effects in dogs and guinea pigs" (PDF). The Journal of Clinical Investigation. 119 (8): 2271–80. doi:10.1172/JCI39115. PMC 2719941. PMID 19620788.
  16. "Hemolytic Anemias, F. Spherocytosis". http://MedicalAssistantOnlinePrograms.org/. Retrieved 6 November 2013. External link in |website= (help)
  17. Mary Anna Thrall, Dale C. Baker, E. Duane Lassen, Veterinary hematology and clinical chemistry, ISBN 0-7817-6850-0, 2004.
  18. Edward F. Gibbons, Barbara Susan Durrant, Jack Demarest, Conservation of endangered species in captivity: an interdisciplinary approach, page 324, 2005, ISBN 0-7914-1911-8
  19. Oliver A. Ryder, Zoological Society of San Diego, Rhinoceros biology and conservation, Zoological Society of San Diego, 1993, page 312, 335.
  20. Texas Monthly, Oct 1992, Vol. 20, No. 10, ISSN 0148-7736, page 98-100.
  21. Jutta Meister, ed. Catharine E. Bell, Encyclopedia of the world's zoos, Volume 3, page 1008, ISBN 1-57958-174-9, 2001.
  22. Kovalkovičová N, Sutiaková I, Pistl J, Sutiak V (2009). "Some food toxic for pets". Interdisciplinary Toxicology. 2 (3): 169–76. doi:10.2478/v10102-009-0012-4. PMC 2984110. PMID 21217849.
External resources
This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.