Rother, phd leonard bell, md peter hillmen, mb, phd mark t. If rate of hemolysis is renal tubule absorptive capacity, free hgb will be excreted in the urine hemoglobinuria. Overview of hemolytic anemia hematology and oncology merck. 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. Immune hemolytic anemia immune hemolytic anemias are mediated by antibod. 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. Intravascular versus extravascular hemolysis usmle forums. The oxidized free heme metheme binds to hemopexin a. Extravascular hemolysis is characterized by removal of circulating rbcs in the.
Complement in hemolytic anemia blood american society. The more common extravascular hemolysis is the removal and destruction of red blood cells with. Destruction of rbc hemolysis normally occurs in reticuloendothelial system. Learn vocabulary, terms, and more with flashcards, games, and other study tools. Daven port transfusion medicine division, department of pathology, university of michigan, ann arbor, michigan. Pdf extravascular hemolysis mimicking severe obstructive. Hemolytic anemia knowledge for medical students and. The mechanism of rbc haemolysis can be intravascular which means destruction of rbc. Extravascular hemolysis definition of extravascular. Intravascular hemolysis article about intravascular. This is a common cause of extravascular hemolysis in the dog. Pdf intravascular hemolysis and the pathophysiology of.
Start studying intravascular and extravascular hemolysis. Find out information about extravascular hemolysis. Oct 09, 2015 additionally, decreased levels of plasma haptoglobin, a marker of rbc destruction, are evidenced1, 2, 3 regardless the site of hemolysis intravascular or extravascular. During intravascular hemolysis, cellfree plasma hemoglobin may overwhelm homeostatic systems in place to remove it. Associate professor, the university of texas medical branch, galveston, tx. Intravascular hemolysis hemoglobin release in the blood haptoglobin levels drop as it tries to capture free hgb hemoglobinuria dark urine extravascular hemolysis buildup of hgb breakdown products conjugating systems of liver are overwhelmed excess unconjugated bilirubin leaks into blood unconjugated bilirubinemia. A case of extravascular hemolysis with tk activatio n. 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 renal impairment. The clinical sequelae of intravascular hemolysis and extracellular. Hemolysis may be an extravascular or an intravascular phenomenon.
Serum ldh is a biomarker of intravascular hemolysis, which releases free hemoglobin and arginase. Paroxysmal nocturnal hemoglobinuria pnh cells are susceptible to hemolysis because of a loss of the complement regulatory proteins cd59 and cd55. Extravascular hemolysis occurs when rbcs are phagocytosed by macrophages in the spleen, liver and bone marrow no free. Extravascular definition and meaning collins english. Hb and altered free complexed haptoglobin balance, and in extravascular cases. In intravascular hemolysis, free hb rapidly removes nitric oxidemalaise, aches, fever, vomiting, abdominal. Jci intravascular hemolysis and the pathophysiology of. Extravascular definition of extravascular by merriamwebster. Context the efficient sequestration of hemoglobin by the red blood cell membrane and the presence of multiple hemoglobin clearance mechanisms suggest a critical need to prevent the buildup of this molecule in the plasma. The spleen usually contributes to hemolysis by destroying mildly abnormal rbcs or cells coated with warm antibodies. In addition to complementmediated intravascular hemolysis, extravascular hemolysis by phagocytosis of opsonized rbc is a major cause of rbc breakdown in aiha. Hemolysis is caused by either abnormalities of the rbcs themselv. 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. Haptoglobin is a plasma protein that irreversibly binds free hemoglobin and is decreased in intravascular hemolysis.
Overview of hemolytic anemia hematology and oncology. Positive coombs test results direct antibody test for c3d three main criteria must be met. Pdf a case of extravascular hemolysis with tkactivation. The macrophages of the reticuloendothelial system in these organs engulf and destroy structurallydefective red blood cells. Hemolytic anemias are typically regenerative and result from lysis of rbcs in either the intra or extravascular space. Intravascular hemolysis during intravascular hemolysis free hemoglobin and heme are released in plasma. This hemolysis occurs primarily in the reticuloendothelial system res.
Extravascular hemolysis in some diseases, hemolysis of rbc occurs within the vascular system. The hemolysis associated with warm aiha is classically extravascular, or occurring in the spleen, although intravascular hemolysis is also common and may account for many of the fulminant cases of warm aiha. 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 hemolysis. Intravenous administration of a hypotonic solution or plain distilled water will also destroy red blood. The clinical sequelae of intravascular hemolysis and. 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. Other words that entered english at around the same time include. Dark urine and intra vs extravascular hemolysis student. 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. There is evidence of free hemoglobin in the serum and free hemoglobin or. Although new red blood cells, or erythrocytes, are continuously created and old ones destroyed, an.
Diagnostic approach to hemolytic anemias in the adult scielo. Apl2, a complement c3 inhibitor, may potentially reduce. Hemolysis and plasma free hemoglobin during extracorporeal. By scavenging free hemoglobin, haptoglobin plays a critical role in preventing free. Schitiocytes are essentially broken up and fragmented rbcs. With extravascular hemolysis, the erythrocytes are degraded within macrophages see image above, so hemoglobin is not released free into the cytoplasm. Intravascular hemolysis produces free hemoglobin, which.
Hemolysis occurs in many hematologic and nonhematologic diseases. In extravascular hemolysis plasma levels of unconjugated bilirubin increase because the hepatocytes cannot process the excess bilirubin. Extravascular hemolysis occurs when rbcs are phagocytosed by macrophages in the spleen, liver and bone marrow no free hgb is released into circulation. Runners can suffer hemolytic anemia due to footstrike hemolysis, the destruction of red blood cells in feet at foot impact. A growing list of clinical manifestations attributed to hemoglobin release. Effect of hemolysis and free hemoglobin on optical hematocri. Lead poisoning or poisoning by arsine or stibine causes nonimmune hemolytic anemia. In investigating the possibility of a druginduced hemolytic anemia, one must consider not only the prescription medications that the patient is taking, but also overthecounter medications and even possible chemical exposures. Haptoglobin is significantly decreased during hemolysis, both in intravascular forms, due to increased free plasma hb and altered free complexed haptoglobin balance, and in extravascular cases, where little intravascular lysis of structurally altered rbc escaped from reticuloendothelial clearance may be present.
Hemolysis is the destruction of red blood cells in the circulation way before their life span is over. It is a manual technique with no automation, requiring technical. Phagocytosis of damaged red cells by macrophages or extravascular hemolysis is not expected to release free hemoglobin or ldh into plasma. There is evidence of free hemoglobin in the serum and free hemoglobin or hemosiderin in the urine i. Thus, we do not see hemoglobinemia or hemoglobinuria with extravascular hemolysis alone, unless it is accompanied by intravascular hemolysis.
Some microbes form substances called hemolysins that have the specific action of destroying red blood cells. Extravascular definition of extravascular by the free. Hemolytic anemias are a group of conditions characterized by the breakdown of red blood cells. Extravascular hemolysis mimicking severe obstructive jaundice. A case of extravascular hemolysis with tkactivation. Extravascular hemolysis is characterized by removal of circulating rbcs in the spleen. Clinical applications of hemolytic markers in the differential. Nov 25, 2017 i have mentioned that hemoglobinhaptoglobin complex forms in the plasma, but this is not true.
Definition of extravascular hemolysis in the medical dictionary by the free dictionary. Hb and altered freecomplexed haptoglobin balance, and in extravascular cases. Acquired hemolytic anemia is also encountered in burns and as a result of certain infections e. In experiments performed at relatively low pumping rates, neither intravascular nor extravascular hemolysis was detected. Hemoglobin defines the clinical severity of hemolysis, and. Intravascular hemolysis results in circulating free hemoglobin.
Extravascular definition is not occurring or contained in body vessels. Lab investigation of hemolysis presentation 91918 ver. Hemolytic anemia osman khan, md assistant professor pediatric hematology oncology leaves the bone marrow as a reticulocyte in 23 days matures into erythrocyte. Complement is increasingly being recognized as an important driver of human disease, including many hemolytic anemias. Free hemoglobin solutions were added in steps to circulating whole blood at baseline hematocrits covering a range from 30% to 60% and at blood flows of. Hemolytic anemia is defined by the premature destruction of red blood cells, and can be chronic or lifethreatening. In this case little hemoglobin escapes into blood plasma.
The presence of significant intravascular hemolysis was always associated with significant extravascular hemolysis. Autoimmune hemolytic anemia and hereditary spherocytosis are examples of extravascular hemolysis because the red blood cells are destroyed in the spleen and other reticuloendothelial tissues. Intravascular hemolysis associated with toxicity is most often immunemediated in origin, typically due to a type ii reaction with fixation by complement membrane attack complex, and lytic pore formation. Nevertheless, if the binding capacities of haptoglobin and hemopexin are saturated, the remaining free hemoglobin in the plasma will be oxidized to methemoglobin eventually, and then further disassociates into free heme and others. Ppt hemolytic anemia powerpoint presentation free to. 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. Sep 15, 2018 hemolytic anemia is defined by the premature destruction of red blood cells, and can be chronic or lifethreatening. Complete this lesson to learn more about what hemolysis is, why it occurs, the symptoms. When large amounts of drug coat the cell surface, the antibody binds the cell membrane and causes extravascular hemolysis. Hemolysis severity, directly appreciated by plasma free hemoglobin concentration, may be present with various intensity, from a nonalarming and tolerable hemolysis to a highly toxic one.
Hemolytic anemia knowledge for medical students and physicians. After completing this article, readers should be able to. Intravascular hemolysis results in hemoglobinemia and hemoglobinuria, whereas extravascular hemolysis does not. Activated c1 triggers the classical complement pathway leading to potentially serious chronic hemolysis8 understand the mechanism and diagnosis of cold agglutinin disease. Classification of common hemolytic anemias extravascular hemolysis is mediated by the reticuloendothelial system res of the spleen and liver. Cellfree plasma haemoglobin may overwhelm this scavenger system causing. 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. Hemolysis due to trauma in the circulation macrovascular. Thereafter, these complexes will undergo the metabolic mechanisms like extravascular hemolysis. Pdf hemolysis is a fundamental feature of sickle cell anemia that contributes to its pathophysiology and phenotypic variability.
Additionally, decreased levels of plasma haptoglobin, a marker of rbc destruction, are evidenced1, 2, 3 regardless the site of hemolysis intravascular or extravascular. The more common extravascular hemolysis is the removal and destruction. Extravascular hemolysis intravascular hemolysis chronic inflammation c1 c5 1. Extravascular hemolysis, on the other hand, is often less dramatic and more insidious in its presentation. Most pathologic hemolysis is extravascular and occurs when damaged or abnormal rbcs are cleared from the circulation by the spleen and liver.
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, but usually in the spleen. Hemolysis is usually described as intravascular hemolysis or extravascular hemolysis. During intravascular hemolysis free hemoglobin and heme are released in plasma. Whereas hemoglobin clearance occurs within the macrophage in extravascular hemolysis, during intravascular hemolysis, circulating free. Erythrocytes may be also destroyed in macrophages extravascular hemolysis or intracellular hemolysis of the mononuclear phagocytic system of the spleen, liver, and bone marrow. Indirect bilirubin is a byproduct of hemoglobin catabolism and is increased in intravascular or extravascular hemolysis. An acquired hemolytic anemia can develop in association with drugs. Subscribe to americas largest dictionary and get thousands more definitions and advanced searchad free. Hemolytic anemia anemia of increased destruction normochromic, normochromic anemia shortened rbc survival reticulocytosis response to increased rbc destruction increased indirect bilirubin increased ldh 3. Intravascular hemolysis an overview sciencedirect topics. Diagnostic approach to hemolytic anemias in the adult. Hemolysis is the destruction of red blood cells before their normal life span is up. Of note, both extravascular and intravascular hemolysis can cause.
A free powerpoint ppt presentation displayed as a flash slide show on id. Extravascular hemolysis refers to hemolysis taking place in the liver, spleen, bone marrow, and lymph nodes. It has numerous possible consequences, ranging from relatively harmless to lifethreatening. Overview of hemolytic anemia msd manual professional edition. Acquired hemolytic anemia an overview sciencedirect topics. Both are integral to the hyperhemolysis model of no scavenging.
Complement c3 inhibition by compstatin cp40 prevents intra. The livers kupffer cells and the spleen are main parts of the reticuloendothelial. Because the fact that rbss are lysed in the blood, its ldh is released into the circulation raising its levels. Gladwin, mdh emoglobin is a highly conserved molecule found in speciesrangingfromsinglecell organisms to mammals, but the role of hemoglobin in different organisms varies. 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.
Free unconjugated bilirubin is transported to the liver where it is conjugated to glucuronic acid. Microspherocytes are evident on the peripheral smear. Extravascular hemolysis article about extravascular. We studied the effect of cp40 on extravascular hemolysis by measuring the phagocytic uptake of opsonized rbc by macrophages. Haemolytic anaemia classification intravascular, extravascular. The quantity of free plasma haptoglobin therefore decreases during.
It should be part of the differential diagnosis for any normocytic or. Attachment of igg or igm causes fixation of complement to c3b on red cell membranes. Most has, such as warm autoimmune hemolytic anemia aiha, sickle cell disease scd, and hereditary spherocytosis hs, are characterized by extravascular hemolysis. The hemoglobin dimers that remain in circulation are oxidized to methemoglobin, which disassociates into a free heme and globin chains.
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