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