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| pronounce =| field = Hematology| symptoms =| complications =| onset =| duration =| types =| causes = Hemolysis| risks =| diagnosis =| differential =| prevention =| treatment =| medication =| prognosis =| frequency =| deaths =}}Hemolytic anemia or haemolytic anaemia 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).BOOK, Capriotti, Theresa, Pathophysiology : introductory concepts and clinical perspectives, Frizzell, Joan Parker, 2016, 978-0-8036-1571-7, Philadelphia, 900626405, This most commonly occurs within the spleen, but also can occur in the reticuloendothelial system or mechanically (prosthetic valve damage). Hemolytic anemia accounts for 5% of all existing anemias. It has numerous possible consequences, ranging from general symptoms to life-threatening systemic effects. The general classification of hemolytic anemia is either intrinsic or extrinsic.WEB,www.chop.edu/conditions-diseases/hemolytic-anemia, Hemolytic Anemia, Philadelphia, The Children’s Hospital of, 2014-03-30, chop.edu, en, 2020-02-25, Treatment depends on the type and cause of the hemolytic anemia.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 gallstonesJOURNAL, Trotman, BW, Pigment gallstone disease., Gastroenterology Clinics of North America, 20, 1, 1991, 0889-8553, 2022417, 111–26, 10.1016/S0889-8553(21)00536-7, and pulmonary hypertension.JOURNAL, Machado, Roberto F., Gladwin, Mark T., Pulmonary Hypertension in Hemolytic Disorders, Chest, Elsevier BV, 137, 6, 2010, 0012-3692, 20522578, 2882115, 10.1378/chest.09-3057, 30S–38S,

Signs and symptoms

Symptoms of hemolytic anemia are similar to the general signs of anemia. General signs and symptoms include fatigue, pallor, shortness of breath, and tachycardia. In small children, failure to thrive may occur in any form of anemia.JOURNAL, Kahre, Tiina, Teder, Maris, Panov, Maarja, Metspalu, Andres, Severe CF manifestation with anaemia and failure to thrive in a 394delTT homozygous patient, Journal of Cystic Fibrosis, Elsevier BV, 3, 1, 2004, 1569-1993, 10.1016/j.jcf.2003.12.009, 15463888, 58–60, free, Hypoproteinemia, Anemia, and Failure to Thrive in an Infant In addition, symptoms related to hemolysis may be present such as chills, jaundice, dark urine, and an enlarged spleen. Certain aspects of the medical history can suggest a cause for hemolysis, such as drugs, medication side effects, autoimmune disorders, blood transfusion reactions, 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.JOURNAL, Levitt, Robert E., Ostrow, Donald J., 1980, Hemolytic Jaundice and Gallstones,www.gastrojournal.org/article/0016-5085(80)90690-3/pdf, Gastroenterology, 78, 4, 821–830, 10.1016/0016-5085(80)90690-3, 7353766, free, 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.JOURNAL, 10.2215/CJN.01960408, Pulmonary Hypertension, Right Ventricular Failure, and Kidney, 2008, Schrier, Robert W., Bansal, Shweta, Clinical Journal of the American Society of Nephrology, 3, 5, 1232–1237, 18614776, 4571151, 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

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.BOOK, McPhee, Stephen J.,books.google.com/books?id=zQlH4mXSziYC&q=hemoglobin+hemosiderin+hemolysis+bilirubin&pg=PT454, CURRENT Medical Diagnosis and Treatment 2009, Papadakis, Maxine A., 2008-10-31, McGraw Hill Professional, 978-0-07-164137-1, en, 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 :

• Defects of red blood cell membrane production (as in hereditary spherocytosis and hereditary elliptocytosis).
• Defects in hemoglobin production (as in thalassemia, sickle-cell disease and congenital dyserythropoietic anemia).
• Defective red cell metabolism (as in glucose-6-phosphate dehydrogenase deficiency and pyruvate kinase deficiency).JOURNAL, Eisa, Mahmoud S., Mohamed, Shehab F., Ibrahim, Firyal, Shariff, Khalid, Sadik, Nagham, Nashwan, Abdulqadir, Yassin, Mohamed A., 2019-11-01, Paroxysmal Nocturnal Hemoglobinuria with Glucose-6-Phosphate Dehydrogenase Deficiency: A Case Report and Review of the Literature, Case Reports in Oncology, 12, 3, 838–844, 10.1159/000503817, 1662-6575, 6873095, 31762758, JOURNAL, Grace, Rachael F., Bianchi, Paola, van Beers, Eduard J., Eber, Stefan W., Glader, Bertil, Yaish, Hassan M., Despotovic, Jenny M., Rothman, Jennifer A., Sharma, Mukta, McNaull, Melissa M., Fermo, Elisa, 2018-05-17, Clinical spectrum of pyruvate kinase deficiency: data from the Pyruvate Kinase Deficiency Natural History Study,ashpublications.org/blood/article/131/20/2183/6537/Clinical-spectrum-of-pyruvate-kinase-deficiency, Blood, en, 131, 20, 2183–2192, 10.1182/blood-2017-10-810796, 29549173, 0006-4971, free,
• Wilson’s disease may infrequently present with hemolytic anemia without due to excessive inorganic copper in blood circulation, which destroys red blood cells (though the mechanism of hemolysis is still unclear).JOURNAL, Sharma, Sunita, Toppo, Anupa, Rath, B., Harbhajanka, Aparna, Lalita Jyotsna, P., Hemolytic Anemia as a Presenting Feature of Wilson’s Disease: A Case Report, Indian Journal of Hematology and Blood Transfusion, September 2010, 26, 3, 101–102, 10.1007/s12288-010-0034-2, 21886393, 3002091,

Extrinsic causes

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

• Immune-mediated causes could include transient factors as in Mycoplasma pneumoniae infection (cold agglutinin disease)JOURNAL, Khoury, Tawfik, Abu Rmeileh, Ayman, Kornspan, Jonathan David, Abel, Roy, Mizrahi, Meir, Nir-Paz, Ran, 2015-02-19, Mycoplasma pneumoniae Pneumonia Associated With Methemoglobinemia and Anemia: An Overlooked Association?, Open Forum Infectious Diseases, 2, 1, ofv022, 10.1093/ofid/ofv022, 2328-8957, 4438901, 26034771, or permanent factors as in autoimmune diseases like autoimmune hemolytic anemiaJOURNAL, Hill, Anita, Hill, Quentin A., 2018-11-30, Autoimmune hemolytic anemia, Hematology, en, 2018, 1, 382–389, 10.1182/asheducation-2018.1.382, 30504336, 6246027, 1520-4391, (itself more common in diseases such as systemic lupus erythematosus, rheumatoid arthritis, Hodgkin’s lymphoma, and chronic lymphocytic leukemia).
• Spur cell hemolytic anemiaPrivitera, G., & Meli, G. (2016). An unusual cause of anemia in cirrhosis: spur cell anemia, a case report with review of literature. Gastroenterology and hepatology from bed to bench, 9(4), 335–339.
• Any of the causes of hypersplenism (increased activity of the spleen), such as portal hypertension.JOURNAL, Li, Hao, Guan, Dongyao, Xu, Junqiang, Jin, Enhao, Sun, Shu, January 2020, Atraumatic splenic rupture was attributed to intra-cystic haemorrhage and hypersplenism in a patient with cirrhosis and portal hypertension: A case report, SAGE Open Medical Case Reports, en, 8, 2050313X2090190, 10.1177/2050313X20901900, 2050-313X, 6984417, 32047630,
• Acquired hemolytic anemia is also encountered in burns and as a result of certain infections (e.g. malaria).JOURNAL, 10.4274/tjh.2017.0466, Spurious thrombocytosis in the setting of hemolytic anemia and microcytosis secondary to extensive burn injury, 2018, Zahid, Mohammad Faizan, Alsammak, Mohamed S., Turkish Journal of Hematology, 35, 3, 205–206, 29391327, 6110454,
• Paroxysmal nocturnal hemoglobinuria (PNH), sometimes referred to as Marchiafava-Micheli syndrome, is a rare, acquired, potentially life-threatening disease of the blood characterized by complement-induced intravascular hemolytic anemia.JOURNAL, Brodsky, Robert A., 2014-10-30, Paroxysmal nocturnal hemoglobinuria, Blood, 124, 18, 2804–2811, 10.1182/blood-2014-02-522128, 0006-4971, 4215311, 25237200,
• Lead poisoning resulting from the environment causes non-immune hemolytic anemia.JOURNAL, Valentine, W N, Paglia, D E, Fink, K, Madokoro, G, October 1976, Lead poisoning: association with hemolytic anemia, basophilic stippling, erythrocyte pyrimidine 5’-nucleotidase deficiency, and intraerythrocytic accumulation of pyrimidines., Journal of Clinical Investigation, 58, 4, 926–932, 10.1172/JCI108545, 0021-9738, 965496, 333255,
• Similarly, poisoning by arsine or stibine also causes hemolytic anemia.JOURNAL, Correia, Nuno, Carvalho, Catarina, Friões, Fernando, Araújo, José P, Almeida, Jorge, Azevedo, Ana, 2009-08-11, Haemolytic anaemia secondary to arsenic poisoning: a case report, Cases Journal, 2, 7768, 10.4076/1757-1626-2-7768, 1757-1626, 2769370, 19918480,
• Runners can develop hemolytic anemia due to “footstrike hemolysis”, owing to the destruction of red blood cells in feet at foot impact.JOURNAL, Telford RD, Sly GJ, Hahn AG, Cunningham RB, Bryant C, Smith JA, Footstrike is the major cause of hemolysis during running, J. Appl. Physiol., 94, 1, 38–42, January 2003, 12391035, 10.1152/japplphysiol.00631.2001, 5750453, JOURNAL, Lippi G, Schena F, Salvagno GL, Aloe R, Banfi G, Guidi GC, Foot-strike haemolysis after a 60-km ultramarathon, Blood Transfus, 377–383, July 2012, 3417738, 22682343, 10.2450/2012.0167-11, 10, 3,
• Low-grade hemolytic anemia occurs in 70% of prosthetic heart valve recipients, and severe hemolytic anemia occurs in 3%.BOOK,books.google.com/books?id=bJF2zgOhJcoC&q=Biomaterials+Engineering+and+Devices-Human+applications+D.L.Wise&pg=PA203, Biomaterials Engineering and Devices: Orthopedic, dental, and bone graft applications, 978-0-89603-859-2, Wise, Donald Lee, 2000, Humana Press, {{Dead link|date=March 2023 |bot=InternetArchiveBot |fix-attempted=yes }}

Mechanism

In hemolytic anemia, there are two principal mechanisms of hemolysis; intravascular and extravascular.Dhaliwal G, Cornett PA, Tierney LM., Jr Hemolytic anemia. Am Fam Physician. 2004;69:2599–606. [PubMed] [Google Scholar]

Intravascular hemolysis

Intravascular hemolysis describes hemolysis that happens mainly inside the vasculature.Stanley L Schrier, MD. William C Mentzer, MD, Jennifer S Tirnauer, MD (eds.). “Diagnosis of hemolytic anemia in the adult”. UpToDate. Archived from the original on 2017-12-26. Retrieved 2019-05-04. As a result, the contents of the red blood cell are released into the general circulation, leading to hemoglobinemia“Intravascular hemolysis”. eClinpath. Retrieved 2019-05-08. and increasing the risk of ensuing hyperbilirubinemia.Muller, Andre; Jacobsen, Helene; Healy, Edel; McMickan, Sinead; Istace, Fréderique; Blaude, Marie-Noëlle; Howden, Peter; Fleig, Helmut; Schulte, Agnes (2006). “Hazard classification of chemicals inducing haemolytic anaemia: An EU regulatory perspective” (PDF). Regulatory Toxicology and Pharmacology. Elsevier BV. 45 (3): 229–241. doi:10.1016/j.yrtph.2006.04.004. hdl:10029/5596. ISSN 0273-2300. PMID 16793184. Retrieved 2019-05-04Intravascular hemolysis may occur when red blood cells are targeted by autoantibodies, leading to complement fixation, or by damage by parasites such as Babesia.“Bilirubin and hemolytic anemia”. eClinpath. Retrieved 2019-05-08.

Extravascular hemolysis

Extravascular hemolysis refers to hemolysis taking place in the liver, spleen, bone marrow, and lymph nodes. In this case little hemoglobin escapes into blood plasma. The macrophages of the reticuloendothelial system in these organs engulf and destroy structurally-defective red blood cells, or those with antibodies attached, and release unconjugated bilirubin into the blood plasma circulation.Rhodes, Carl E.; Varacallo, Matthew (2019-03-04). “Physiology, Oxygen Transport”. NCBI Bookshelf. PMID 30855920. Retrieved 2019-05-04.’Sokol RJ, Hewitt S, Stamps BK (June 1981). “Autoimmune haemolysis: an 18-year study of 865 cases referred to a regional transfusion centre”. Br Med J (Clin Res Ed). 282’(6281): 2023–7. doi:10.1136/bmj.282.6281.2023. PMC 1505955. PMID 6788179. Typically, the spleen destroys mildly abnormal red blood cells or those coated with IgG-type antibodies,BRAUNSTEIN.EVAN (2019-05-03). “Overview of Hemolytic Anemia – Hematology and Oncology”. Merck Manuals Professional Edition (in Latin). Retrieved 2019-05-05.“Hypersplenism: MedlinePlus Medical Encyclopedia”. MedlinePlus. 2019-04-30. Retrieved 2019-05-08.’’ while severely abnormal red blood cells or those coated with IgM-type antibodies are destroyed in the circulation or in the liver.If extravascular hemolysis is extensive, hemosiderin can be deposited in the spleen, bone marrow, kidney, liver, and other organs, resulting in hemosiderosis.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.JOURNAL, Bosman, Giel J. C. G. M., 2013, Survival of red blood cells after transfusion: processes and consequences, Frontiers in Physiology, 4, 376, 10.3389/fphys.2013.00376, 1664-042X, 3866658, 24391593, free, {{Unreliable medical source|date=June 2020}} 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.JOURNAL, Alaarg, Amr, Schiffelers, Raymond M., van Solinge, Wouter W., van Wijk, Richard, 2013, Red blood cell vesiculation in hereditary hemolytic anemia, Frontiers in Physiology, 4, 365, 10.3389/fphys.2013.00365, 1664-042X, 3862113, 24379786, free, {{Unreliable medical source|date=June 2020}} 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 pentose phosphate pathway (PPP) for the materials needed to reduce oxidative damage. Any limitations of PPP can result in more susceptibility to oxidative damage and a short or abnormal lifecycle.JOURNAL, Kosenko, Elena A., Tikhonova, Lyudmila A., Montoliu, Carmina, Barreto, George E., Aliev, Gjumrakch, Kaminsky, Yury G., 2018-01-05, Metabolic Abnormalities of Erythrocytes as a Risk Factor for Alzheimer’s Disease, Frontiers in Neuroscience, 11, 728, 10.3389/fnins.2017.00728, 1662-453X, 5760569, 29354027, free, {{Unreliable medical source|date=June 2020}} If the cell is unable to signal to the reticuloendothelial phagocytes by externalizing phosphatidylserine, it is likely to lyse through uncontrolled means.JOURNAL, Kolb S, Vranckx R, Huisse MG, Michel JB, Meilhac O, The phosphatidylserine receptor mediates phagocytosis by vascular smooth muscle cells, The Journal of Pathology, 212, 3, 249–59, July 2007, 17534843, 10.1002/path.2190, 22923550, JOURNAL, Bosman GJ, Willekens FL, Werre JM, Erythrocyte aging: a more than superficial resemblance to apoptosis?, Cellular Physiology and Biochemistry, 16, 1–3, 1–8, 2005, 16121027, 10.1159/000087725, 2066/47441, 188974,repository.ubn.ru.nl/bitstream/2066/47441/1/47441.pdf, free, JOURNAL, Bratosin D, Mazurier J, Tissier JP, etal, Cellular and molecular mechanisms of senescent erythrocyte phagocytosis by macrophages. A review, Biochimie, 80, 2, 173–95, February 1998, 9587675, 10.1016/S0300-9084(98)80024-2, 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.BOOK, Hillman, Robert S.,books.google.com/books?id=NJs1VpA8SEoC&q=hemoglobin+hemosiderin+hemolysis+bilirubin&pg=PA138, Hematology in Clinical Practice, Ault, Kenneth A., Rinder, Henry, June 2005, McGraw Hill Professional, 978-0-07-144035-6, en, BOOK, Greer, John P.,books.google.com/books?id=68enzUD7BVgC&q=hemoglobin+hemosiderin+hemolysis+bilirubin&pg=PA161, Wintrobe’s Clinical Hematology, 2008, Lippincott Williams & Wilkins, 978-0-7817-6507-7, en, WEB, Bradencarter,www.thestackerz.com/hemolytic-anemia-types-causes-symptoms-treatment/, What is Hemolytic Anemia?, thestackerz.com, 21 January 2017, 21 January 2017, 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. 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.JOURNAL, Boretti FS, Buehler PW, D’Agnillo F, etal, 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, August 2009, 19620788, 2719941, 10.1172/JCI39115,www.zora.uzh.ch/20201/1/Boretti_2009_JVIM_Comparison1.pdf, 2018-10-31, 2022-02-11,www.zora.uzh.ch/id/eprint/20201/1/Boretti_2009_JVIM_Comparison1.pdf," title="web.archive.org/web/20220211025436www.zora.uzh.ch/id/eprint/20201/1/Boretti_2009_JVIM_Comparison1.pdf,">web.archive.org/web/20220211025436www.zora.uzh.ch/id/eprint/20201/1/Boretti_2009_JVIM_Comparison1.pdf, dead,

Diagnosis

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 (also called direct antiglobulin test or DAT) to evaluate complement factors and/or antibodies binding to red blood cells:(File:Algorithm in positive direct antiglobulin test (DAT, or direct Coombs test).png|500px|thumb|center|Algorithm for the main diagnoses in a positive DAT, using C3 to represent complement factors, and IgG as antibody type.Image by Mikael Häggström, MD. Source for conditions: WEB,www.bbguy.org/2017/02/27/028/, 028: Who DAT? with Sue Johnson, Joe Chaffin, 2017-02-27, Citing: C Feldman & J O’Connor.)

Treatment

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).WEB,www.medicalassistantonlineprograms.org/hemolytic-anemias/, Hemolytic Anemias, F. Spherocytosis, MedicalAssistantOnlinePrograms.org/, 6 November 2013, 8 January 2015,www.medicalassistantonlineprograms.org/hemolytic-anemias/," title="web.archive.org/web/20150108181659www.medicalassistantonlineprograms.org/hemolytic-anemias/,">web.archive.org/web/20150108181659www.medicalassistantonlineprograms.org/hemolytic-anemias/, dead,

Mitapivat was approved for medical use in the United States in February 2022.PRESS RELEASE, Agios Announces FDA Approval of Pyrukynd (mitapivat) as First Disease-Modifying Therapy for Hemolytic Anemia in Adults with Pyruvate Kinase Deficiency, Agios Pharmaceuticals, GlobeNewswire, 17 February 2022,www.globenewswire.com/news-release/2022/02/17/2387542/31990/en/Agios-Announces-FDA-Approval-of-PYRUKYND-mitapivat-as-First-Disease-Modifying-Therapy-for-Hemolytic-Anemia-in-Adults-with-Pyruvate-Kinase-Deficiency.html, 19 February 2022,

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.Mary Anna Thrall, Dale C. Baker, E. Duane Lassen, Veterinary hematology and clinical chemistry, {{ISBN|0-7817-6850-0}}, 2004.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.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}}Oliver A. Ryder, Zoological Society of San Diego, Rhinoceros biology and conservation, Zoological Society of San Diego, 1993, page 312, 335.Texas Monthly, Oct 1992, Vol. 20, No. 10, ISSN 0148-7736, page 98-100. The disease is also found in wild rhinos.Jutta Meister, ed. Catharine E. Bell, Encyclopedia of the world’s zoos, Volume 3, page 1008, {{ISBN|1-57958-174-9}}, 2001.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.JOURNAL, Kovalkovičová N, Sutiaková I, Pistl J, Sutiak V, Some food toxic for pets, Interdisciplinary Toxicology, 2, 3, 169–76, 2009, 21217849, 2984110, 10.2478/v10102-009-0012-4,

References

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External links

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