Extravascular hemolysis does not cause hemoglobinemia and hemoglobinuria but usually causes hemolytic icterus. Amino acids from the globin chains are recycled and the fe removed from the heme and reused. Scott koepsell, md, phd autoimmune hemolytic anemia is a rare disorder caused by autoreactive red blood cell rbc antibodies that destroy rbcs. Intravascular hemolysis in pnh, for example results in hemoglobinuria following saturation of haptoglobin. Pdf diagnostic approach to hemolytic anemias in the adult. We present an unusual case of red urine in a 20yearold male who was subsequently diagnosed with intravascular hemolysis due to an aortoatrial fistula. Splenectomy can be used in the management of some hematological diseases, such as bthalassemia, to reduce spleendriven extravascular hemolysis 14.
When a patient presents with anemia, a stepwise approach should be followed. Extravascular hemolysis refers to hemolysis taking place in the liver, spleen. How do gsh and g6pd interact to protect rbc membrane from damage by oxidants. Extravascular definition of extravascular by medical dictionary. The spleen usually contributes to hemolysis by destroying mildly abnormal rbcs or cells coated with warm antibodies. Hemolysis may occur in vivo or in vitro inside or outside the body one cause of hemolysis is the action of hemolysins, toxins that are produced by certain pathogenic. This doesnt occur in extravascular hemolysis because the reticuloendothelial system is active. Hemolytic anemia knowledge for medical students and. Hemolysis, breakdown or destruction of red blood cells so that the contained oxygencarrying pigment hemoglobin is freed into the surrounding medium. Decreased levels of haptoglobin, a hemoglobinbinding protein that is rapidly cleared from the circulation, is.
Extravascular hemolysis intravascular hemolysis chronic inflammation c1 c5 1. The clinical sequelae of intravascular hemolysis and. Hemolysis of transfused rbcs is the major sequelae prevented by crossmatching blood prior to transfusion. Intravascular hemolysis may occur when red blood cells are targeted by autoantibodies, leading to complement fixation, or by damage by parasites such as babesia. Alloimmmune hemolytic anemia hemolytic disease of newborn incompatible blood transfusion 3. Blood is a vital liquid that lows through your veins and arteries. This oftenupdated app combines a large number of pdf files from your android device, as well as many other useful features. Find out information about extravascular hemolysis. Most has, such as warm autoimmune hemolytic anemia aiha, sickle cell disease scd, and hereditary spherocytosis hs, are characterized by extravascular hemolysis. Hemolytic anemia caused by shortening of the red cell life span the red cells may break down in the reticuloendothelial system i.
Attachment of igg or igm causes fixation of complement to c3b on red cell membranes. Hemolytic anemia anemia of increased destruction normochromic, normochromic anemia shortened rbc survival reticulocytosis response to increased rbc destruction increased indirect bilirubin increased ldh. Red cell destruction may occur chiefly in the reticuloendothelial system extravascular hemolysisthe usual situation in most types of hemolytic anemia or in the blood intravascular hemolysisuncommon, largely restricted to physical lysis of red cells, as in microangiopathy, or to complementmediated lysis, or in some combination of the. Extravascular hemolysis occurs when rbcs are phagocytized by macrophages in the spleen, liver and bone marrow see image of an erythrophage to the right. Click, drag, and drop to reorder files or press delete to remove any content you dont want. On the other hand deficiency of pyruvate kinase leads to extravascular hemolysis by splenic macrophages. Autoimmune hemolytic anemia is initially treated with highdose corticosteroids, typically oral at 1 to 2 milligramskg per day for 3 to 4 weeks, with improvement expected in 80% to 85% of patients but complete remission in only up to 30% of patients. The phenomena leading to in vivo hemolysis can be categorized as intravascular and extravascular hemolysis on the basis of the site of red blood cell destruction. Effects of cellfree plasma hemoglobin and nitric oxide no depletion during intravascular hemolysis.
Premature destruction of red cells may result from corpuscular abnormalities within the red cell corpuscle, that is, abnormalities of membrane. With picmonic, get your life back by studying less and remembering more. Activated c1 triggers the classical complement pathway leading to potentially serious chronic hemolysis8 understand the mechanism and diagnosis of cold agglutinin disease. Nonimmune hemolytic anemia microangiopathic hemolytic anemiasdic,ttp,hus trauma. The engulfed hemoglobin is converted into iron for recycling and the globine portion becomes billirubin later. Oxidants can damage rbc membrane causing hemolysis, gsh is a reducing agent that removes oxidants in rbc, process is as follows. Most often causes by deposition of fibrin strands from coag system, intra and extravascular hemolysis.
Hemoglobin is the most direct indicator of clinical severity in hemolytic diseases. Extravascular hemolysis article about extravascular. G6pd hemolysis is predominantly intravascular as hemolysis is due to increase oxidant stress inside rbc. Approach to a case of extracorpuscular hemolytic anemia dr.
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. The peripheral blood smear displays abnormal rbc morphology consistent with hemolysis. In severe immune reactions, large numbers of antibodies attach to the. In cats however, imha has been reported less often and, in. 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. The unconjugated bilirubin is elevated, as is the lactate dehydrogenase ldh, reflecting rbc breakdown. Gillette, md, new york the existence of hemolysis in sickle cell disease has been documented by both indi rect and direct methods. Immunemediated hemolytic anemia imha in cats part 1. Start studying intravascular and extravascular hemolysis. Despite this precaution, occasionally one observes the hemolysis of crossmatchcompatible blood. Classification of common hemolytic anemias extravascular hemolysis is mediated by the reticuloendothelial system res of the spleen and liver. In extravascular hemolysis, the peripheral smear will show microspherocytes or with cold agglutinins, erythrocyte agglutination if the blood is not warmed upon collection. Pdf intravascular hemolysis and the pathophysiology of. The association of acute pancreatitis and hemolysis is less widely appreciated than the association of pancreatitis with lipemic serum.
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. Without c5b, the membrane attack complex does not form, and pnh red cells are protected from intravascular hemolysis. Basic functionality is available without a fee, while an adfree experience can be had with inapp purchases. Gladwin, mdh emoglobin is a highly conserved molecule found in speciesrangingfromsinglecell organisms to mammals, but the role of hemoglobin in different organisms varies. In some cases, an intravascular htr and an immediate extravascular reaction may occur concurrently. Diagnostic approach to hemolytic anemias in the adult ncbi. Extravascular or intravascula r two basi mechanismc explais thn immune e destruction of red blood cells. Extravascular hemolysis refers to hemolysis taking place in the liver, spleen, bone marrow, and lymph nodes. Positive coombs test results direct antibody test for c3d three main criteria must be met. You need a significant amount of hemolysis chronic hemolysis to overload the liver increased bilirubin in urine. Many patients with invasive infections with this organism develop significant hemolysis, but the mechanism has been unclear. Intravascular hemolysis is a rare but potentially life threatening cause of red urine characterized by brisk hemolysis and release of large amounts of hemoglobin into the urine. Erythrocytes may be also destroyed in macrophages extravascular hemolysis or intracellular hemolysis of the mononuclear phagocytic system of the spleen, liver, and bone marrow. Anemia occurs when your body makes too few rbcs, destroys too.
Several hemolytic markers are available to guide the differential diagnosis and to monitor treatment of hemolytic conditions. Clinical applications of hemolytic markers in the differential. 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. The laboratory findings characteristic of acquired hemolytic anemia demonstrate hemolysis of rbcs, hemoglobin breakdown, and compensatory rbc production table 2371. Hemolysis is usually described as intravascular hemolysis or extravascular hemolysis.
What links here related changes upload file special pages permanent link. Immediate or acute extravascular htrs occur either during the transfusion or within a few. 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. Hemolysis or haemolysis also known by several other names, is the rupturing lysis of red. Dark urine and intra vs extravascular hemolysis student. Extravascular hemolysis mimicking severe obstructive jaundice. 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. Tables 71 and 72 list the causes of hemolytic anemia due to corpuscular and extracorpuscular defects, respectively. The capsular polysaccharide of hemophilus influenzae type b, polyribosyl ribitol phosphate prp, is released from growing organisms during human infection and can be found in body fluids. Intravascular versus extravascular hemolysis usmle forums. Hemolytic anemia approach to diagnosis an essential feature of hemolytic anemia is a reduction in the normal red cell survival of 120 days. Autoimmune hemolytic anemia warm antibodies cold anti bodies 2.
The presence of significant intravascular hemolysis was always associated with significant extravascular hemolysis. The more common extravascular hemolysis is the removal and destruction of red blood cells with membrane alterations by the mac rophages of the spleen and. 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. Intravascular hemolysis is an important part of many anemias depending on its severity, hemolysis may contribute to vascular complications pulmonary hypertension, stroke, blood clots, leg ulcers, priapism screening strategies and treatments have been developed in scd. After completing this article, readers should be able to.
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. This is a common cause of extravascular hemolysis in the dog. Pathophysiology of hemolysis in infections with hemophilus. Persistent hemolysis in a patient with pancreatitis. Although autoimmune hemolytic anemia is rare, rbc autoantibodies are encountered frequently and. Some degree of hemolysis is acceptable and expected. Extravascular hemolysis after transfusion progressively increased with. Intravascular hemolysis refer to breakdown of red cells in the circulating blood. Hemolysis of stored red cells is a normal process and increases with storage times. Diagnostic approach to hemolytic anemias in the adult. While hemolysis can be a lifelong asymptomatic condition, it most often. Explain the role of immune reactions, red blood cell membrane defects, red blood cell enzyme defects, or hemoglobin abnormalities in the development of hemolytic anemia. Daven port transfusion medicine division, department of pathology, university of michigan, ann arbor, michigan. Hemolysis is characterized by a compensatory reticulocytosis.
Bilirubin, produced in the periphery, is transported to the liver tightly bound to albumin namely, unconjugated bilirubin. Its levels may be close to normal values in mild forms hb 10 gdl or importantly reduced in moderate hb 810 gdl, severe hb 68 gdl, and very severe hb 6 gdl forms. Red cells coated with igg and c3b will be mainly sequestered by macrophages in the liver, but splenic macrophages may also be involved. Learn vocabulary, terms, and more with flashcards, games, and other study tools.
The existence of bonemarrow erythroid hyperplasia, reticu locytosis, indirect hyperbilirubinemia, and elevations of plasma hemoglobin and serum lactic acid dehydrogenase values. Nov 25, 2017 i have mentioned that hemoglobinhaptoglobin complex forms in the plasma, but this is not true. Hemolytic anemias are a group of conditions characterized by the breakdown of red blood cells. How to merge pdfs and combine pdf files adobe acrobat dc. Jan 18, 2012 this feature is not available right now. Group of disorderscharacterized by fragmentation of rbcs as they pass through abnormal arterioles, resulting in intravascular hemolysis. Hemolysis can be caused by an acquired or inherited condition. Extravascular hemolysis is more common with rbc membrane disorders such as hereditary spherocytosis. Pdf extravascular hemolysis mimicking severe obstructive. Extravascular hemolysis is always present in an animal with a hemolytic anemia in animals. Laboratory demonstration of the presence of a hemolytic process 3. Associate professor, the university of texas medical branch, galveston, tx.
Re d bloo celld coats ed wit igh g ar destroyee primarild in thy e. Intravascular hemolysis and the pathophysiology of sickle cell disease article pdf available in journal of clinical investigation 1273. Extravascular hemolysis definition of extravascular. 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. Classification of hemolytic anemias 2 extracorpuscular factors immune hemolytic anemias autoimmune hemolytic anemia transfusion of incompatible blood nonimmune hemolytic anemias chemicals bacterial infections, parasitic infections malaria, venons hemolysis due to physical trauma hemolytic uremic syndrome hus. 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. Anemia healthy changes national heart, lung, and blood. Consequent complement activation can impact the clinical picture and is an emerging target for therapeutic approaches. Macrophages possess receptors for the fc portion of igg and igm as well as for c3b, thus causing red blood cells with attached immunoglobulin or c3b to be phagocytized. In 2007, eculizumab became the first us food and drug administration fdaapproved drug for the treatment of pnh. 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. Click add files and select the files you want to include in your pdf. This hemolysis occurs primarily in the reticuloendothelial system res. Overview of hemolytic anemia hematology and oncology.
Schistocytes and other poikilocytes seen, degree of hemolysis correlates with amount of thrombosis present. You can merge pdfs or a mix of pdf documents and other files. They include increased reticulocytes, an indicator of marrow compensatory response, elevated lactate dehydrogenase, a marker of intravascular hemolysis, reduced haptoglobin, and unconjugated hyperbilirubinemia. Pdf a case of extravascular hemolysis with tkactivation. With extravascular hemolysis which is normally how effete rbc are removed from the circulation, i. In some cases, hemolysis of crossmatchcompatible blood is an immunemediated mechanism that involves undetected antibodies. Moreover, it is essential to distinguish the acute or chronic characteristics of anemia, the features of intra or extravascular hemolysis, and the. The livers kupffer cells and the spleen are main parts of the reticuloendothelial. 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. Jun 01, 2004 hemolysis is the destruction or removal of red blood cells from the circulation before their normal life span of 120 days. Despite some limitations in the free edition of this app, including a maximum file size of 2.
Even though hemolytic anemias has are not very common, their diagnosis. Prolonged red cell storage before transfusion increases. Hemolysis is the break down of red cells and the subsequent release of hemoglobin, the pigmented protein in red cells. Rother, phd leonard bell, md peter hillmen, mb, phd mark t. Hemopoiesis increase to compensats e for red bloo celd losl s the norma lifl e spa n of red blood cell iss 100. Autoimmune hemolytic anemia aiha is a decompensated acquired hemolysis caused by the hosts immune system acting against its own red cell antigens. Rearrange individual pages or entire files in the desired order. Intravascular hemolysis secondary to aortoatrial fistula. In a recent large retrospective study of 308 cases of primary aiha, hemoglobin values at diagnosis were the.
Why are intravascular and extravascular hemolysis dangerous. 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. Autoimmune hemolytic anemia and red blood cell autoantibodies erin quist, md. Most pathologic hemolysis is extravascular and occurs when damaged or abnormal rbcs are cleared from the circulation by the spleen and liver. Extravascular hemolysis occurs when red cells are coated with antibody or complement and are taken up macrophages and destroyed outside the circulating blood. Although new red blood cells, or erythrocytes, are continuously created and old ones destroyed, an. Hazard classification of chemicals inducing haemolytic anaemia. The clinical sequelae of intravascular hemolysis and extracellular.