Jci intravascular hemolysis and the pathophysiology of. G6pd deficiency function of g6pd infections drugs 2 h2o h2o2 hgb sulfhgb gssg 2 gsh nadph nadp heinz bodies6pg g6pd g6p hemolysis. Quizlet flashcards, activities and games help you improve your grades. African variantmildly reduced halflife of g6pd leading to mild intravascular hemolysis with oxidative stress 2. It is an autosomal dominant disease which is a result of. 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. The drug has been implicated in hemolysis due to the formation of immune complexes. Thus, some g6pd variants associated with severe enzyme deficiency, such as union and markham, cause no hemolytic problem, while some variants associated with less severe deficiency, such as manchester, alhambra, and tripler, cause chronic hemolytic anemia. There are numerous causes of hemolytic anemia, including inherited and acquired conditions, acute and chronic processes, and mild to potentially lifethreatening severity. Aihaautoimmune hemolytic anemia, g6pdglucose6phosphate dehydrogenase. Extravascular and intravascular hemolysis, as well as decreased rbc. Red blood cell breakdown may be triggered by infections, certain medication, stress, or foods such as fava beans. There are a few reported cases of acalypha indica ingestion induced hemolysis in g6pd deficient people. It is an xlinked recessive disorder that results in defective glucose6phosphate dehydrogenase enzyme.
G6pd hemolysis is predominantly intravascular as hemolysis is due to increase oxidant stress inside rbc. Hemolysis may be either intravascular or extravascular. Extravascular hemolysis, on the other hand, is often less dramatic and more insidious in its presentation. The hemoglobin is released into the blood and immediately bound by haptoglobin for clearance in the liver.
Extravascular hemolysis is always present in an animal with a hemolytic anemia in animals. There are numerous causes of hemolytic anemia, including inherited and. G6pd deficiencyfun fact about itwhat kind of mutation is. Acalypha indica is a tropical plant used as a medicinal plant as well as a vegetable. In fact, we were unable to find any reports of hydralazineinduced hemolysis in g6pd deficiency. Hemolytic anemias due to erythrocyte enzyme deficiencies.
Glucose6phosphate dehydrogenase deficiency wikipedia. 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. Microspherocytes are evident on the peripheral smear. Decompartmentalized hemoglobin, arginase 1, asymmetric dimethylarginine, and adenine nucleotides are all products of hemolysis that promote vasomotor dysfunction, proliferative vasculopathy, and a multitude of clinical complications of pulmonary and. Overview of hemolytic anemia hematology and oncology. Dic, shock, renal failure, death chronic hemolysis. Survey on causes of hemolysis in glucose6phosphate. On the other hand deficiency of pyruvate kinase leads to extravascular hemolysis by splenic macrophages. Thalassemias are known to cause extravascular hemolysis. G6pd deficiency with hemolytic anemia due to a rare gene. Depending on the specific mutation the severity of the condition may vary. The best characterized exogenous triggers of hemolysis in g6pddeficient subjects are, apart from infection, fava beans and drugs.
Signs of hemolysis that are typically associated with intravascular hemolysis only and not extravascular hemolysis include all of the following except. 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. Hemolytic anemias are a group of conditions characterized by the breakdown of red blood cells. Intravascular hemolysis occurs when erythrocytes are destroyed in the blood vessel.
When g6pddeficient rbcs are exposed to primaquine, or when normal rbcs are treated with phenylhydrazine, hemolysis is primarily extravascular, due to macrophage ingestion in the spleen and liver. In this report we describe a rare coexistence of severe intravascular hemolysis in a patient with hepatitis e infection and. In some patients with some diseases, it may be accompanied by intravascular hemolysis luckily this does not happen too often as intravascular hemolysis is bad for a patient because it can cause acute renal injury. In intravascular hemolysis, free hb rapidly removes nitric oxidemalaise, aches, fever, vomiting, abdominal pain. Glucose6phosphate dehydrogenase deficiency leads to hemolysis in. Glucose6phosphate dehydrogenase g6pd deficiency is an xlinked enzymatic defect common in blacks, which can result in hemolysis after acute illnesses or intake of oxidant drugs including salicylates and sulfonamides. Selected early and sensitive indicators of oxidative damage prodromal of extravascular and intravascular hemolysis were analyzed time dependently in hemizygous and heterozygous g6pddeficient subjects after ingestion of 500 g lowvc raw fb seeds per 70 kg body weight ie, 510 times the amount of an average fb meal. Diagnosis is based on assay for g6pd, although tests are often falsely negative during acute hemolysis. Blacks often have an episodic variant in which oxidant compounds such as antimalarials, sulfonamides, or infections cause hemolysis. Hemolytic anemia knowledge for medical students and. The direct antiglobulin test dat, also known as the direct coombs test, demonstrates the presence of.
Hemolytic anemia the student source university of virginia. However, this mechanism is unlikely to be responsible for the acute intravascular hemolysis seen. Intravascular hemolysis is also suggested by urinary hemosiderin. Glucose6phosphate dehydrogenase deficiency youtube. Hemolysis is the destruction of red blood cells in the circulation way before their life span is over.
Glucose6phosphate dehydrogenase deficiency, or g6pd deficiency, is a genetic disorder characterized by decreased levels of glucose6phosphate dehydrogenase, which leads to the destruction of. There is evidence of free hemoglobin in the serum and free hemoglobin or hemosiderin in the urine i. 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 hemolysis is suggested by rbc fragments schistocytes on the peripheral smear and by decreased serum haptoglobin levels. Intermittent hemolysis in spite of severe g6pd deficiency, e.
Though there can be an element of extravascular hemolysis in g6pd deficiency with the formation of heinz bodies from denatured hemoglobin passing through the reticuloendothelial system, the primary hemolysis in g6pd deficiency is intravascular and accounts for the increased ldh and decreased haptoglobin seen in the patient. Some forms of hemolytic anemia feature both intravascular and extravascular. Other select causes of acquired hemolysis not discussed in this article include splenomegaly, endstage liver diseasespur cell acanthocyte hemolytic anemia, paroxysmal cold hemoglobinuria, paroxysmal nocturnal hemoglobinuria, insect stings, and spider bites. The information available at present 2017 about g6pd deficiency prevalence and.
Diagnostic approach to hemolytic anemias in the adult ncbi. Intravascular versus extravascular hemolysis usmle forums. The severity of enzyme deficiency often does not correlate well with the clinical severity of genetic diseases. 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 more common extravascular hemolysis is the removal and. Intermittent hemolysis associated usually with drugsinfections and moderate g6pd deficiency, e. Acquired hemolytic anemia an overview sciencedirect topics. Other causes of hemolysis were usage of oxidative drugs, infections, pollen of fava beans and diabetic ketoacidosis. Fava beans was also reported as the major cause of 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. Hemolysis may occur predominantly in the spleen extravascular or in the vessels intravascular with intravascular hemolysis, why are serum haptoglobin levels are reduced. Intravascular hemolysis occurs in hemolytic anemia due to the following. Glucose6phosphate dehydrogenase g6pd deficiency is a wellknown, xlinked genetic disorder that most commonly affects up to 25% of primarily male patients from africa, asia, and the mediterranean.
Diagnostic approach to hemolytic anemias in the adult. Intravascular hemolysis is the destruction of red blood cells in the. Pdf intravascular hemolysis and the pathophysiology of. Hemolysis can occur in people with g6pd deficiency under oxidative stress. Even though hemolytic anemias has are not very common, their diagnosis. An understanding of this is important for physician assistant exam pance purposes. This most commonly occurs within the spleen, but also can occur in the reticuloendothelial system or mechanically prosthetic valve damage. Diagnosis of hemolytic anemia in the adult uptodate.
G6pd deficiency is characterized primarily by c1intravascular hemolysis however, extravascular hemolysis occurs as well due to consumption by macrophages sketchy path says that intravascular hemolysis is less prominent than extravascular hemolysis. Hemolytic anemia ppt presentation linkedin slideshare. G6pd deficiency primarily intra or extra vascular hemolysis. A rare and unusual acquired hematologic disorder characterized by intravascular hemolysis bone marrow failure cytopenias thrombosis. In intravascular hemolysis rbcs lyse in the circulation releasing hemoglobin into the plasma. Mediterranean variantmarkedly reduced halflife of g6pd leading to marked. Intravascular hemolysis and the pathophysiology of sickle cell disease article pdf available in journal of clinical investigation 1273. Extravascular hemolysis is characterized by removal of circulating rbcs in the spleen.
Extravascular and intravascular hemolysis, as well as decreased rbc recovery, were reported in subjects transfused with rbcs from g6pddeficient donors when the recipients were treated with a hemolysisinducing drug. Intravascular hemolysis the rbcs are lysed within the blood vessel such as by mechanical damage of a heart valve, or because of complement fixation as in paroxysmal nocturnal hemoglobinuria. Intravascular hemolysis are caused by the following. Medications to avoid in patients with g6pd deficiency due. Favism and hemolytic anemia in g6pddeficient subjects in. Glucose6phosphate dehydrogenasedeficiency in transfusion. Effect of highdose vitamin c infusion in a glucose6. Additionally, decreased levels of plasma haptoglobin, a marker of rbc destruction, are evidenced1, 2, 3 regardless the site of hemolysis intravascular or extravascular. Hemolytic anemia is defined as anemia due to a shortened survival of circulating red blood cells rbcs due to their premature destruction. Clinical spectrum and severity of hemolytic anemia in. Hemolysis is a fundamental feature of sickle cell anemia that contributes to its pathophysiology and phenotypic variability. The case highlights the need for a high degree of suspicion of g6pd deficiency in patients with unexplained signs and symptoms of intravascular hemolysis.
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