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.
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).
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. 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).
Hereditary (inherited) hemolytic anemia can be due to :
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
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. 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.
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. 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. 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.
Hemolytic anemia may affect non human species as well. It has been found in a number of animal species to result from specific triggers.
Some notable cases include hemolytic anemia found in black rhinos kept in captivity, with the disease affecting 20% of the animals in one instance. The disease is also found in wild rhinos.
^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 Pathology212 (3): 249–59. doi:10.1002/path.2190. PMID17534843.
^Bosman GJ, Willekens FL, Werre JM (2005). "Erythrocyte aging: a more than superficial resemblance to apoptosis?". Cellular Physiology and Biochemistry16 (1–3): 1–8. doi:10.1159/000087725. PMID16121027.
^Bratosin D, Mazurier J, Tissier JP, et al. (February 1998). "Cellular and molecular mechanisms of senescent erythrocyte phagocytosis by macrophages. A review". Biochimie80 (2): 173–95. doi:10.1016/S0300-9084(98)80024-2. PMID9587675.
^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 Acids70 (1): 77–83. doi:10.1016/j.plefa.2003.08.006. PMID14643182.
^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 Acta1427 (2): 175–82. doi:10.1016/S0304-4165(99)00023-9. PMID10216234.
^Yamato O, Hayashi M, Yamasaki M, Maede Y (February 1998). "Induction of onion-induced haemolytic anemia in dogs with sodium n-propylthiosulphate". The Veterinary Record142 (9): 216–9. doi:10.1136/vr.142.9.216. PMID9533293.
^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 Research53 (1): 134–7. PMID1539905.
^Murase T, Maede Y (April 1990). "Increased erythrophagocytic activity of macrophages in dogs with Babesia gibsoni infection". Nippon Juigaku Zasshi52 (2): 321–7. doi:10.1292/jvms1939.52.321. PMID2348598.
^Ogawa E, Shinoki T, Akahori F, Masaoka T (August 1986). "Effect of onion ingestion on anti-oxidizing agents in dog erythrocytes". Nippon Juigaku Zasshi48 (4): 685–91. doi:10.1292/jvms1939.48.685. PMID3761777.
^Harvey JW, Rackear D (July 1985). "Experimental onion-induced hemolytic anemia in dogs". Veterinary Pathology22 (4): 387–92. PMID4035943.
^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. PMID7175912.