On the other hand deficiency of pyruvate kinase leads to extravascular hemolysis by splenic macrophages. Pdf intravascular hemolysis and the pathophysiology of. Complement in hemolytic anemia blood american society of. Autoimmune hemolytic anemia hematology and oncology. Learn vocabulary, terms, and more with flashcards, games, and other study tools. Autoimmune hemolytic anemia aiha is caused by the increased destruction of red blood. In extravascular hemolysis rbcs are phagocytized by macrophages in the spleen and liver. Hey got2study, i revised it, actually both of them cause increase urinary urobilinogen, but non of them causes bilirubin in the urin, the only deffirence is signs of intravascular hemolysis signs of intra or extravascular hemolysis. Causes include rbc membrane abnormalities such as bound immunoglobulin, or physical abnormalities restricting rbc deformability that prevent egress from the spleen.
Severely abnormal rbcs or rbcs coated with cold antibodies or complement c3 are destroyed within the circulation and in the liver. The oxidized free heme metheme binds to hemopexin a. Immune hemolytic anemia immune hemolytic anemias are mediated by antibod. As indicated above, extravascular hemolysis is always occurring and is usually seen alone without intravascular hemolysis. Nov 25, 2017 i have mentioned that hemoglobinhaptoglobin complex forms in the plasma, but this is not true. Start studying intravascular and extravascular hemolysis. Laboratory evaluation begins with examination of the peripheral blood smear. Decreased levels of haptoglobin, a hemoglobinbinding protein that is rapidly cleared from the circulation, is. In the hemolytic conditions, ldh mainly isoenzymes 1 and 2 is often increased and may be useful to distinguish extravascular versus intravascular hemolysis, being slightly increased in the former e. Pathogenesis and mechanisms of antibodymediated hemolysis. Hemolytic anemia in animals circulatory system merck. Extracellular hemoglobin hb has been found to trigger specific pathophysiologies that are associated with adverse clinical outcomes in patients with hemolysis, such as acute and chronic vascular disease, inflammation, thrombosis, and. Extravascular pool since 100% of the hemoglobin was converted to unconj bilir lets say we have 100 unconj. The unconjugated bilirubin is elevated, as is the lactate dehydrogenase ldh, reflecting rbc breakdown.
Reduced nitric oxide production by l arginine deficiency in lysinuric protein intolerance exacerbates intravascular. The hemoglobin dimers that remain in circulation are oxidized to methemoglobin, which disassociates into a free heme and globin chains. Yes, the bilirubin passing through the canaliculi is predominantly conjugated, and only trace amounts of unconjugated. Some microbes form substances called hemolysins that have the specific action of destroying red blood cells. How we reduced hemolyzed specimens throughout our hospital and. The clinical sequelae of intravascular hemolysis and extracellular. Common causes of extravascular hemolysis include autoimmune hemolytic anemia and hereditary disorders. Rother, phd leonard bell, md peter hillmen, mb, phd mark t. Premature destruction of red cells may result from corpuscular abnormalities within the red cell corpuscle, that is, abnormalities of membrane. Extravascular hemolysis definition of extravascular. Some countries have limited the maximum allowable storage duration for red cells to 5 weeks before transfusion. Hemolytic anemias are typically regenerative and result from lysis of rbcs in either the intra or extravascular space. Intravascular versus extravascular hemolysis usmle forums.
Extravascular hemolysis article about extravascular. Additionally, intravascular hemolysis may occur due to complementinduced mac formation on the rbc membrane as a consequence of strong complement. In the us, red blood cells can be stored for up to 6 weeks, but randomized trials have not assessed the effects of this final week of storage on clinical outcomes. A case of extravascular hemolysis with tkactivation. Although new red blood cells, or erythrocytes, are continuously created and old ones destroyed, an. Extravascular hemolysis occurs when rbcs are phagocytized by macrophages in the spleen, liver and bone marrow see image of an erythrophage to the right. Intravascular hemolysis may occur when red blood cells are targeted by autoantibodies, leading to complement fixation, or by damage by parasites such as babesia. The direct antiglobulin direct coombs test establishes the diagnosis and may suggest the cause. Intravenous administration of a hypotonic solution or plain distilled water will also destroy red blood. Intravascular vs extravascular hemolysis and the color of. If the damage is severe enough, immediate lysis occurs within the circulation intravascular hemolysis if the damage is less severe, the cell is destroyed within the monocytemacrophage system in the spleen, liver, bone marrow, and lymph nodes extravascular hemolysis iv. The clinical sequelae of intravascular hemolysis and. Intravascular hemolysis in pnh, for example results in hemoglobinuria following saturation of haptoglobin.
In this case little hemoglobin escapes into blood plasma. Extravascular hemolysis is characterized by spherocytes. Intravascular hemolysis results in hemoglobinemia and hemoglobinuria, whereas extravascular hemolysis does not. Amino acids from the globin chains are recycled and the fe removed from the heme and reused. The livers kupffer cells and the spleen are main parts of the reticuloendothelial system. Gladwin, mdh emoglobin is a highly conserved molecule found in speciesrangingfromsinglecell organisms to mammals, but the role of hemoglobin in different organisms varies. Hemolysis in the intravascular compartment results in a greater elevation of plasma. Reduced nitric oxide production by larginine deficiency in lysinuric protein intolerance exacerbates intravascular. We use some laboratory features to identify when intravascular hemolysis is occurring with extravascular hemolysis, as summarized in the table below. Dec 27, 2015 bilirubin is a good marker for extravascular and, to a lesser extent, also for intravascular hemolysis, where a minor fraction of the released heme binds to hemopexin and undergoes reticuloendothelial catabolism in the liver. Intravascular hemolysis may occur when red blood cells are targeted by. Rickard, bs, mtascp preanalytical manager your story tellers charlotte damato six sigmalean quality coach charlene h.
This hemolysis occurs primarily in the reticuloendothelial system res. Splenectomy is also employed to reduce extravascular hemolysis in hs, and a recent. Hemolytic anemia the student source university of virginia. Serum tests include ldh, haptoglobin, bilirubin, and reticulocyte count. Hemolysis occurs in many hematologic and nonhematologic diseases. So you can see why bilirubin would accumulate, not hgb. Hemolysis occurs normally in a small percentage of red blood cells as a means of removing aged cells from the bloodstream and freeing heme for iron. Extravascular hemolysis is always present in an animal with a hemolytic anemia in animals. Pdf a case of extravascular hemolysis with tkactivation. Splenectomy removes the largest reservoir of reticuloendothelial macrophages, and this may result in extended red cell survival, but perhaps more likelihood that the eventual demise of the red cell will be via intravascular hemolysis, rather than extravascular.
Dark urine and intra vs extravascular hemolysis student. 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. Hemolysis is the destruction or removal of red blood cells from the circulation before their normal life span of 120 days. Extravascular hemolysis occurs solely because macrophages are killing more rbcs. You need a significant amount of hemolysis chronic hemolysis to overload the liver increased bilirubin in urine. In intravascular hemolysis rbcs lyse in the circulation releasing hemoglobin into the plasma. A combination of all of these tests can give insight into whether or note hemolytic anemia is present and, if present, the degree of hemolysis. Intravascular hemolysis is the state when the red blood cell ruptures as a result of the complex of complement autoantibodies attached fixed on the surfaces of rbcs attack and rupture rbcs membranes, or a parasite such as babesia exits the cell that ruptures the rbcs membrane as it goes.
G6pd hemolysis is predominantly intravascular as hemolysis is due to increase oxidant stress inside rbc. Hemolytic anemia is a prominent part of the clinical presentation of patients infected with organisms such as the plasmodium sp. Under most circumstances, the diagnosis of intravascular hemolysis. Autoimmune hemolytic anemia is caused by autoantibodies that react with red blood cells at temperatures. When the rbcs are prematurely removed from the circulation and destroyed by the macrophages in the spleen and liver, it is referred to as extravascular. I have mentioned that hemoglobinhaptoglobin complex forms in the plasma, but this is not true.
Followup of partial splenectomy in children with hereditary. How we reduced hemolyzed specimens throughout our hospital and what we do to sustain those gains dana j. When large amounts of drug coat the cell surface, the antibody binds the cell membrane and causes extravascular hemolysis. Find out information about extravascular hemolysis. Hemolysis can occur due to different causes and leads to the release of hemoglobin into the bloodstream. Patients with atypical hemolytic uremic syndrome ahus develop a. Jun 01, 2004 hemolysis is the destruction or removal of red blood cells from the circulation before their normal life span of 120 days. Most pathologic hemolysis is extravascular and occurs when damaged or abnormal rbcs are cleared from the circulation by the spleen and liver. A case of extravascular hemolysis with tk activatio n. Such hemolysis following transfusion is reliably avoided in a donorrecipient pair, if one individual is negative for the cognate antigen to which the other has the antibody.
Hemolysis is caused by either abnormalities of the rbcs themselves abnormalities in hemoglobin, the rbc membrane or intracellular enzymes, also called corpuscular anemia, or by external causes immunemediated or mechanical damage, which is referred to as extracorpuscular anemia. Hemolytic anemia knowledge for medical students and. In dogs, the most common cause of hemolytic anemia is immune. Jci prolonged red cell storage before transfusion increases. Haematologica is, therefore, epublishing pdf files of an early version of manuscripts that. While hemolysis can be a lifelong asymptomatic condition, it most often. Hemolysis is the destruction of red blood cells in the circulation way before their life span is over. Immunemediated hemolytic anemia imha results from an immunemediated destruction of red blood cells rbcs that causes a decrease in the total rbc mass and often leads to life threatening anemia. Hemolytic anemia laboratory findings on the web most recent articles. Common causes include microangiopathic processes such as hemolytic uremic syndrome, or hus. Fa says extravascular, and of course has no explanation, because its fa.
Pleiotropic effects of intravascular hemolysis on vascular. In cats however, imha has been reported less often and, in. Malaria is the most common cause of hemolytic anemia on a worldwide basis, and much has been learned about how the parasite enters the erythrocyte and the mechanism of anemia. The potential adverse effects of haemolysis request pdf. Extravascular definition of extravascular by medical. Intravascular hemolysis is the destruction of red blood cells occurring intravascularly, or within the circulation. Extravascular hemolysis refers to hemolysis taking place in the liver, spleen, bone. Overview of hemolytic anemia msd manual professional edition. Occurs within monocytes and macrophage, also known as res. Bilirubin, produced in the periphery, is transported to the liver tightly bound to albumin namely, unconjugated bilirubin. The reticuloendothelial system is the part of the immune system consisting of cells whose job is to engulf and remove defective blood cells from the circulation. This most commonly occurs within the spleen, but also can occur in the reticuloendothelial system or mechanically prosthetic valve damage. Hemolysis resulting from highdose penicillin therapy is an example of the drugabsorption mechanism, in which a medication attached to the red blood membrane stimulates igg antibody production.
Gee six pee dee deficiency intraextravascular hemolysis. Request pdf the potential adverse effects of haemolysis. Most clinically relevant antibodies can be detected by sensitive in vitro assays. Hemolysis or haemolysis also known by several other names, is the rupturing lysis of red. The spleen usually contributes to hemolysis by destroying mildly abnormal rbcs or cells coated with warm antibodies. The engulfed hemoglobin is converted into iron for recycling and the globine portion becomes billirubin later.
Hemolysis is characterized by a compensatory reticulocytosis. This doesnt occur in extravascular hemolysis because the reticuloendothelial system is active. Understanding the intra and extravascular contri butions to the bold effect through simulations j. A deficiency of g6pd must be considered in the differential diagnosis of intra and extravascular hemolysis 7. Extravascular definition of extravascular by medical dictionary. Hemolytic anemia anemia of increased destruction normochromic, normochromic anemia shortened rbc survival reticulocytosis response to increased rbc destruction increased indirect bilirubin increased ldh. The degree of intravascular hemolysis is 10fold greater than extravascular one. Hemolysis may be either intravascular or extravascular.
So in rr path it says g6pd deficiency often leads to intravascular hemolysis, but im not sure the explanation given was really even relevant. Transfusion of packed red blood cells prbcs can result in intravascular haemolysis, in which the rbcs are destroyed within the circulation, and extravascular. Extravascular hemolysis refers to hemolysis taking place in the liver, spleen, bone marrow, and lymph nodes. Hemolysis, breakdown or destruction of red blood cells so that the contained oxygencarrying pigment hemoglobin is freed into the surrounding medium. By needle aspiration of the spleen in sickle cell patients, lichtman et al28 demonstrated that there was an increased number ofcells in the sickled shape encountered in the spleen as compared to the peripheral circulation. Normal red blood cells erythrocytes have a lifespan of about 120 days. Hb metabolism partly occurs in tissue macrophages, which can engulf senescent erythrocytes extravascular hemolysis or take up hb released from ruptured erythrocytes intravascular hemolysis and immature erythrocytes in the bone marrow. Several mechanisms of antibodymediated hemolysis are well understood. Hemolysis is usually described as intravascular hemolysis or extravascular hemolysis. The macrophages of the reticuloendothelial system in these organs engulf and destroy structurallydefective red blood cells. Apr 19, 2017 intravascular hemolysis hemoglobin release in the blood haptoglobin levels drop as it tries to capture free hgb hemoglobinuria dark urine is due to just hb extravascular hemolysis buildup of hgb breakdown products conjugating systems of liver are overwhelmed excess unconjugated bilirubin leaks into blood unconjugated bilirubinemia now, understand that. Objectives lab indication of hemolysis intravascular vs extravascular hemolysis dd of hemolytic anemia diagnose hemo. New insights in the pathogenesis of autoimmune hemolytic anemia.
Immunemediated hemolytic anemia imha in cats part 1. In extravascular hemolysis spleen and liver macrophage fc receptors bind immunoglobulin attached to rbcs and then either ingest small portions of the rbc membrane creating spherocytes or phagocytizing the rbcs. Now back to all the unconjugated bilirubin we have from our intra and extravasc hemolysis so lets say we have 2 pools 1. Understanding the intra and extravascular contributions. Complement c3 inhibition by compstatin cp40 prevents intraand. Decreased levels of haptoglobin, a hemoglobinbinding protein that is rapidly cleared from the circulation, is a more specific indicator of rbc bre. Hemolytic anemia approach to diagnosis an essential feature of hemolytic anemia is a reduction in the normal red cell survival of 120 days. Rbcs are coated with antibodies or have abnormal shape of membrane or abnormal inclusion such as heinz bodies in g6pd and so they are attacked prematurely by the liver and spleen phagocytes. A case of paroxysmal nocturnal hemoglobinuria caused by a. Overview of hemolytic anemia hematology and oncology. Extravascular hemolysis rbcs are coated with antibodies or have abnormal shape of membrane or abnormal inclusion such as heinz bodies in g6pd and so they are attacked prematurely by the liver and spleen phagocytes.
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