Hemolytic anemia

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Hemolytic anemia
Classification and external resources
ICD-10 D55-D59
ICD-9 282, 283, 773
DiseasesDB 5534
MedlinePlus 000571
eMedicine med/979
MeSH D000743

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). It has numerous possible causes, 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.

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 and pulmonary hypertension.

Basic features[edit]

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.

Signs and symptoms[edit]

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. 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. The continuous release of free hemoglobin has been linked with the development of pulmonary hypertension (increased pressure over the pulmonary artery); 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).

Causes[edit]

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.[1] 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[edit]

Hereditary (inherited) hemolytic anemia can be due to :

Extrinsic causes[edit]

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

Pathophysiology[edit]

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, and be excreted in the urine causing the urine to become a dark brown color.

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. It is perhaps then helpful to understand the physiology of the RBC and things that can go wrong to cause it to "die" prematurely. 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.[5][6][7] 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 onion or garlic.[8][9][10][11][12][13][14][15][16][17]

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.[18][19] Free hemoglobin can bind to haptoglobin, or it 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.[18] 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.[20]

Diagnosis[edit]

Treatment[edit]

Definitive therapy depends on the cause:

  • Symptomatic treatment can be given by blood transfusion, if there is marked anemia.
  • In severe immune-related hemolytic anemia, steroid therapy is sometimes necessary.
  • 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).[21]

Veterinary cases[edit]

Hemolytic anemia affects nonhuman species as well as humans. It has been found, in a number of animal species, to result from specific triggers.[22]

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.[23][24][25] The disease is also found in wild rhinos.[26]

References[edit]

  1. ^ Current Medical Diagnosis and Treatment 2009 By Stephen J. McPhee, Maxine A. Papadakis page 436 http://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
  2. ^ 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. 
  3. ^ Lippi G, Schena F, Salvagno GL, Aloe R, Banfi G, Guidi GC (July 2012). "Foot-strike haemolysis after a 60-km ultramarathon". Blood Transfus: 377–383. PMC 3417738. 
  4. ^ Wise, Donald Lee (2000). Biomaterials Engineering and Devices: Orthopedic, dental, and bone graft applications. ISBN 978-0-89603-859-2. 
  5. ^ 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. 
  6. ^ Bosman GJ, Willekens FL, Werre JM (2005). "Erythrocyte aging: a more than superficial resemblance to apoptosis?". Cellular Physiology and Biochemistry 16 (1–3): 1–8. doi:10.1159/000087725. PMID 16121027. 
  7. ^ 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. 
  8. ^ Chang HS, Yamato O, Sakai Y, Yamasaki M, Maede Y (January 2004). "Acceleration of superoxide generation in polymorphonuclear leukocytes and inhibition of platelet aggregation by alk(en)yl thiosulfates derived from onion and garlic in dogs and humans". Prostaglandins, Leukotrienes, and Essential Fatty Acids 70 (1): 77–83. doi:10.1016/j.plefa.2003.08.006. PMID 14643182. 
  9. ^ Yamato O, Hayashi M, Kasai E, Tajima M, Yamasaki M, Maede Y (April 1999). "Reduced glutathione accelerates the oxidative damage produced by sodium n-propylthiosulfate, one of the causative agents of onion-induced hemolytic anemia in dogs". Biochimica et Biophysica Acta 1427 (2): 175–82. doi:10.1016/S0304-4165(99)00023-9. PMID 10216234. 
  10. ^ Yamato O, Hayashi M, Yamasaki M, Maede Y (February 1998). "Induction of onion-induced haemolytic anemia in dogs with sodium n-propylthiosulphate". The Veterinary Record 142 (9): 216–9. doi:10.1136/vr.142.9.216. PMID 9533293. 
  11. ^ Yamoto O, Maede Y (January 1992). "Susceptibility to onion-induced hemolysis in dogs with hereditary high erythrocyte reduced glutathione and potassium concentrations". American Journal of Veterinary Research 53 (1): 134–7. PMID 1539905. 
  12. ^ Murase T, Maede Y (April 1990). "Increased erythrophagocytic activity of macrophages in dogs with Babesia gibsoni infection". Nippon Juigaku Zasshi 52 (2): 321–7. doi:10.1292/jvms1939.52.321. PMID 2348598. 
  13. ^ Ogawa E, Shinoki T, Akahori F, Masaoka T (August 1986). "Effect of onion ingestion on anti-oxidizing agents in dog erythrocytes". Nippon Juigaku Zasshi 48 (4): 685–91. doi:10.1292/jvms1939.48.685. PMID 3761777. 
  14. ^ Harvey JW, Rackear D (July 1985). "Experimental onion-induced hemolytic anemia in dogs". Veterinary Pathology 22 (4): 387–92. PMID 4035943. 
  15. ^ van Schouwenburg S (September 1982). "[Hemolytic anemia in a miniature dashshund caused by eating large amounts of onion (Allium cepa)]". Journal of the South African Veterinary Association (in Afrikaans) 53 (3): 212. PMID 7175912. 
  16. ^ Stallbaumer M (June 1981). "Onion poisoning in a dog". The Veterinary Record 108 (24): 523–4. doi:10.1136/vr.108.24.523. PMID 7257143. 
  17. ^ Spice RN (July 1976). "Hemolytic anemia associated with ingestion of onions in a dog". The Canadian Veterinary Journal. La Revue Vétérinaire Canadienne 17 (7): 181–3. PMC 1697286. PMID 949673. 
  18. ^ a b Hematology in clinical practice: a guide to diagnosis and management By Robert S. Hillman, Kenneth A. Ault, Henry M. Rinder page 136-139 http://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
  19. ^ Wintrobe's Clinical Hematology, Volume 1 By John P. Greer http://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
  20. ^ 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". The Journal of Clinical Investigation 119 (8): 2271–80. doi:10.1172/JCI39115. PMC 2719941. PMID 19620788. 
  21. ^ "Hemolytic Anemias, F. Spherocytosis". http://MedicalAssistantOnlinePrograms.org/. Retrieved 6 November 2013. 
  22. ^ Mary Anna Thrall, Dale C. Baker, E. Duane Lassen, Veterinary hematology and clinical chemistry, ISBN 0-7817-6850-0, 2004.
  23. ^ 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
  24. ^ Oliver A. Ryder, Zoological Society of San Diego, Rhinoceros biology and conservation, Zoological Society of San Diego, 1993, page 312, 335.
  25. ^ Texas Monthly, Oct 1992, Vol. 20, No. 10, ISSN 0148-7736, page 98-100.
  26. ^ Jutta Meister, ed. Catharine E. Bell, Encyclopedia of the world's zoos, Volume 3, page 1008, ISBN 1-57958-174-9, 2001.