Intrinsic cell wall defect of RBCs is feature of?
Ans. C. Hereditary spherocytosis > A. Paroxysmal Nocturnal Hemoglobinuria. (Ref, H-17th/pg. 665, 660)H - 17th. Pg. 655:In HEREDITARY SPHEROCYTOSIS the basic defect in the membrane-cytoskeleton structure.The membrane-cytoskeieton complex is so integrated that, an abnormality of almost any of its components will be disturbing or disruptive, causing structural failure, which results ultimately in hemolysis. These abnormalities are almost invariably inherited mutations, and thus diseases of the membrane-cytoskeleton complex belong to the category of inherited hemolytic anemias. Before the red cells lyse, they often exhibit changes that alter the normal biconcave disc shape. Thus, the majority of the diseases in this group have been known for over a century as hereditary spherocytosis (HS) and hereditary elliptocytosis (HE). Their molecular basis has been elucidated.H-17th. Pg. 660:" Hemolysis in PNH is due to an intrinsic abnormality of the red cell which makes it exquisitely sensitive to activatedComlement, whether it is activated through the alternative pathway or through an antigen-antibody reaction.The former mechanism is mainly responsible for IV hemolysis in PNH . "Discussion:Paroxysmal Nocturnal Hemoglobinuria (PNH)Introduction:# PNH is an acquired chronic Hemolytic Aanemia characterized by persistent intravascular hemolysis subject to recurrent exacerbations, and TRIAD: hemolysis + pancytopenia + risk of venous thrombosis.# There is no evidence of inherited susceptibility. PNH has never been reported as a congenital disease, but it can present in small children or in people in their seventies, although most patients are young adults.Pathophysiology:# Shortage of a unique glycolipid molecule, GPI, which, through a peptide bond, anchors these proteins to the surface membrane of cells. The shortage of GPI is due in turn to a mutation in an X-linked gene, called PIG-A, required for an early step in GPI biosynthesis. In virtually each patient, the PIG-A mutation is different.# An element of bone marrow failure (BMF) in PNH is the rule rather than the exception.C/f:# PNH has about the same frequency in men and women.# TRIAD of hemolysis, pancytopenia, and venous thrombosis makes PNH a truly unique clinical condition;2# Without Rx, the median survival is -8-10 years; in the past the commonest cause of death has been venous thrombosis followed by infection secondary to severe neutropenia and hemorrhage secondary to severe thrombocytopenia.2# PNH may evolve into aplastic anemia (AA), and PNH may manifest in patients who previously had AA.# Rarely (estimated 1-2% of all cases), PNH may terminate in acute myeloid leukemia.# On the other hand, full spontaneous recovery from PNH has been well documented, albeit rarely.LAB Diagnosis:# The most consistent blood finding is anemia, which may range from mild to moderate to very severe.# The anemia is usually normo-macrocytic, with unremarkable red cell morphology; if the MCV is high, it is largely accounted for by reticulocytosis, which may be quite marked (up to 20%, or up to 400,000/iL).# Neutropenia and/or thrombocytopenia may or may not be present from the outset or develop subsequently.# Following findings make the diagnosis of Hemolytic Aanemia compelling:Q- Unconjugated bilirubin is mildly or moderately elevated,0- LDH is typically markedly elevated (values in the thousands are common), and- Haptoglobin is usually undetectable.# The definitive diagnosis of PNH must be based on the demonstration that a substantial proportion of the patient's red cells have an increased susceptibility to complement (C), due to the deficiency on their surface of proteins (particularly CD59 and CD55) that normally protect the red cells from activated C.# The sucrose hemolysis test is unreliable, and the acidified serum (Ham) test is carried out in few labs.# The gold standard today is flow cytometry, which is carried out on granulocytes or on red cells.- A bimodal distribution of cells, with a population that is CD59- CD55-, is diagnostic of PNH.Diseases/ Clinical Situations with Predominantly Intravascular Hemolysis:DiseaseOnset/ Time CourseMain MechanismAppropriate Diagnostic ProcedureCommentsMismatched blood transfusionAbruptNearly always ABO incompatibilityRepeat cross match-Paroxysmal nocturnal hemoglobinuria (PNH)Chronic with acute exacerbationsComplement (C)- mediated destruction of CD59(-) red cellsFlow cytometry to display a CD59(-) red cell populationExacerbations due to C activation through any pathwayParoxysmal cold hemoglobinuria (PCH)AcuteImmune lysis of normal red cellsTest for Donath- Landsteiner antibodyOften triggered by viral infectionSepticemiaVery acuteExotoxins produced by Clostridium perfringensBlood culturesOther organisms may be responsibleMicroangiopathicAcute or chronicRed cell fragmentationRed cell morphology on blood smearDifferent causes ranging from endothelial damage to hemangioma to leaky prosthetic heart valveMarch hemoglobinuriaAbruptMechanical destructionTargeted history taking-FavismAcuteDestruction of older fraction of G6PD-deficient red cellsG6PD assayTriggered by ingestion of large dish of fava beans; but trigger can be infection or drug insteadRx:# Unlike other acquired HAs, PNH may be lifelong and most patients receive supportive Rx only, including transfusion of filtered red cells2 whenever necessary.# Long-term glucocorticoids are not indicated because there is no evidence that they have any effect on chronic hemolysis, and their side effects are considerable and potentially dangerous.# The onh form of Rx that can provide a cure for PNH is allogeneic bone marrow transplantation (BMT); when an HLA-identical sibling is available, BMT should be offered to any young patient with severe PNH.# A major advance in the management of PNH has been the development of a humanized monoclonal antibody, Eculizumab (intravenously at q2wk intervals), directed against the complement protein C5.
Paroxysmal Nocturnal Hemoglobinuria
Sickle cell disease
Hereditary spherocytosis
All of the above
Blood