RED CELL DISORDERS Anemia of blood loss Hemolytic anemia Anemia of decreased erythropoiesis Polycythemia Bleeding disorders Bleeding disorders related

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  • Blood LossAcute: traumaChronic: lesions of gastrointestinal tract, gynecologic disturbances. The features of chronic blood loss anemia are the same as iron deficiency anemia, and is defined as a situation in which the production cannot keep up with the loss.

  • Acute blood loss result in Hypovolemic shockThere is normocytic nromochromic anemiaDecreased in hematocritIncreased erythropoisis and reticulocytosisThere is leuckocytosis due to mobilization by adrenergic hormones in turn due to hypotension compensatory release of adrenergic hormones, thrombocytosis.

  • HEMOLYTICHEREDITARYMEMBRANE disorders: e.g., spherocytosisENZYME disorders: e.g., G6PD deficciencyHGB disorders (hemoglobinopathies)ACQUIREDMEMBRANE disorders (PNH)ANTIBODY MEDIATED, transfusion or autoantibodiesMECHANICAL TRAUMAINFECTIONSDRUGS, TOXINSHYPERSPLENISM

  • IMPAIRED PRODUCTIONDisturbance of proliferation and differentiation of stem cells: Aplastic anemias, Pure RBC aplasia, Renal failure

  • Disturbance of proliferation and maturation of erythroblasts

    Defective DNA synthesis: (Megaloblastic Anemia), deficiency of folate and Vitamin B12

  • Defective heme synthesis: (Fe) Iron deficiency anemiaDeficient globin synthesis: Thalassemias

  • Increased Destruction (Hemolytic Anemias) Intrinsic (intracorpuscular) abnormalities.Hereditary Membrane abnormlities Membrane skeleton proteins: H.Spherocytosis, H.Elliptocytosis

  • Enzyme deficiencies Glycolytic enzymes: pyruvate kinase, Hexokinase Enzymes of hexose monophosphate shunt: glucose-6-phosphate dehydrogenase, glutathione synthetase

  • Disorders of hemoglobin synthesis Deficient globin synthesis: thalassemia syndromes Structurally abnormal globin synthesis (hemoglobinopathies): sickle cell anemia, unstable hemoglobins

  • Acquired Membrane defect: paroxysmal nocturnal hemoglobinuria

  • Extrinsic(extracorpuscular)abnormalities Antibody mediated Isohemagglutinins: transfusion reactions, erythroblastosis fetalis (Rh disease of the newborn) Autoantibodies: idiopathic (primary), drug-associated, systemic lupus erythematosus

  • Mechanical trauma to red cells

    Microangiopathic hemolytic anemias: thrombotic thrombocytopenic purpura, disseminated intravascular coagulation Infections: malariaToxins like clostodium toxinMarathon running and drumbeatingChemical injury like lead poisoningHypersplenism and defective cardiac valves.

  • Mechanical traumaRed blood cell fragments, burr cells, and helmet cells are associated with eithermicroangiopathic hemolytic anemia or mechanical red cell destruction.In patients with prosthetic valves, red blood cells are exposed to excessive shear and turbulencein the circulation, causing damage from mechanical trauma


  • Classification depending on Red cell sizeNormocyticMicrocyticMacrocyticDegree of hemoglobinization the color of the red cellNormochromicHypochromicHyperchromic

  • Mean cell volume(MCV) is average volume of red cell expressed in femtolt(FL)Normal-82 to96 flDecreased in iron def anemia

  • Mean cell hb(MCH) is average mass of the Hb expressed in PicogramNormal 27 to37 picogramDecreased in iron deficiency anemia

  • MCHC(Mean cell Hb concentration) is average concentation of Hb in a given packed red cell. Male-33-37g/dl female-33-37g/dlRDW Red cell distribution width 11.5-14.5

  • Hemoglobin- men-13.6-17.2 g/dl women-12.0-15.0 g/dlHematocrit (HCT) Men- -39-49% women- 33-43% Red cell count 106/mm3 Men4.3-5.9 Women-3.5-5.0 Reticulocyte count 0.5-1.5%

  • Hemolytic anemiaAnemia's that are associated with accelerated destruction of red cells are termed hemolytic anemias.Destruction can be caused by either inherent (intracorpuscular) red cell defects, which are usually inherited, or external (extracorpuscular) factors, which are usually acquired

  • HEMOLYTIC ANEMIASGeneral features of hemolytic anemias. (1) an increased rate of red cell destruction, (2) a compensatory increase in erythropoiesis that results in reticulocytosis, and (3) Accumulation of Hb degradation products

  • Intravascular hemolysisDestruction of red cells can occur within the vascular compartmentExtravascular hemolysis.Red cell destruction within the cells of the mononuclear phagocyte (reticuloendothelial) system

  • Clinical features of extra vascular hemolysisExtravascular hemolysis needs alteration in RBC shape to less deformable to pass thro the spllenic sinusoidsFeatures1.Anemia2.Jaundice 3.Splenomegaly.

  • Intravascular hemolysis causesMechanical traumaBy defective cardiac valves thrombotic Narrowing of the microcirculationComplement fixationIntracellualr parasites(Malarial parasite)Toxic injuries

  • Clinical features

    1.Anemia2.Hbglobinemia3.Hemoglobinuria4.Hemosiderinuria. Massive intravascular hemolysis sometimes leads to acute tubular necrosis (Free iron damamging the tubular cells)

  • HEMOGLOBIONURIALarge amount of Hb is released from the lysed RBCs bound to heptoglobin cleared by MNPS and depletion of heptoglobin occurs and remaining free Hb oxidizes to methhemoglobin which is brown in color causing when excreted in urine give rise to hemoglobinuria

  • JaundiceHb bounded to heptoglobin form complex is cataboliseed to bilirubin in MNPs leads to jaundice.The heme converts to conjugated and uncongugated bilirubin and excess of unconjugated bilirubin leads to icterus.

  • HemosiderosisSome Hb release iron which accumulates in renal tubular cells cause renal hemosiderosis.(also renal tubular necrosis)

  • There is a raise in uncongugated bilirubin in hemolytic anemiaAlso formation of gall stones.

  • Hereditary Spherocytosis

    The inherited disorder is caused by the intrinsic defect in the red cell membrane skeleton that leads RBC to spheroid,and vulnerable to splenic sequestration and destruction.It is a Autosomal dominant, in of the cases.Common in Northern Europe25% of patients have a more severe autosomal recessive form of the disease.

  • PATHOGENESISIn HS the primary abnormality resides in one of a group of proteins.The major protein in this skeleton is spectrin,The mutations is that they weaken the vertical interactions between the membrane skeleton and the intrinsic membrane proteins

  • Hereditary spherocytosisMild to moderatehemolytic anemia can lead to splenomegaly, jaundice, and pigmented gallstones..common defect involves mutations in the gene that codes for ankyrin

  • In all types of HS the red cells have reduced membrane stability and consequently lose membrane fragments after their release into the periphery, Blood smears showasSpherocytosisReticulocytosisRaised MCHC due to dehydration caused by loss of H2o and K

  • Clinical Course anemia, splenomegaly, and jaundice.Because of their spheroidal shape, HS red cells show increased osmotic fragility when placed in hypotonic salt solutions, a characteristic that is helpful for diagnosisPigment stones 40 to 50% of the cases

  • Complications

    Complications 1. Aplastic crisis due to Infection by parvovirus2.Hemolytic crisis3.Gall stonesTreatmentSplenectomy

  • HEREDITARY SPHEROCYTOSISGenetic defects affecting ankyrin, spectrin, usually autosomal dominant

    Children, adults

    Anemia, hemolysis, jaundice, splenomegaly, gallstones (what kind?)

  • Glucose-6-Phosphate Dehydrogenase Deficiency

    Red cells are subjected to injuries by exo or endogenous oxidantsAny abnormality in HMP shunt or glutathione metabolism result in deficient in enzyme function and reduces RBC to protect themselvs against oxidants and leads to hemolysis

  • G6PD genetic variants are,G6PD AAnd G6PD Mediterranean, most common in Middle east countries and clinically more significant.

  • Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency

    A- and Mediterranean are most significant types

  • G6PD is a X linked recessive disorderMost of these cases are harmless.The deficiency is caused by exposure that generate oxidative stressMainly infectionsViral hepatitisPneumoniaTyphoid fever

  • Drugs and certain foods like fava beansDrugs areAntimalarialsSulfonamidesNitrofurantoinIt can cause both intra and extravascular hemolysis

  • G6 PD deficiency anemiaHeinz bodies consist of denatured HbFava beans

  • G6PD


  • G6PD functionsRegenerates NADPH, allowing regeneration of glutathioneProtects against oxidative stressLack of G6PD leads to hemolysis during oxidative stressInfectionMedicationsFava beansOxidative stress leads to Heinz body formation, extravascular hemolysis

  • Presence of Heinz bodies is hall mark of G6Pd deficiencyOxidants cause cross linking of sulfhydryl groups on globin chain and denature and membrane bound precipitates called as Heinz bodies also responsible for intravascular hemolysis and less deformable leads to extravascular hemolysis.

  • The hemoglobinopathiesThe hemoglobinopathies are a group of hereditary disorders that are defined by the presence of structurally abnormal hemoglobins Sickle Cell Anemia It is a common herditary Hb nopathy occurs primarily in individuals of African descent.

    On average, the normal adult red cell contains 96% HbA (22), 3% HbA2 (22), and 1% fetal Hb (HbF, 22).

  • SICKLE CELL ANEMIASickle cell anemia is caused by mutations in globin gene.Substitution of valine for glutamic acid at the sixth position of the -chain produces HbSAbout 8 to 10% of African American are heterozygous individuals it remain asymptomatic as sickle cell trait.

  • Etiology and Pathogenesis

    Etiology and Pathogenesis Upon de oxygenation, Hb S molecules undergo polymerization, a process also referred to as gelation or crystallization. These polymers distort the red cell, which assumes an elongated crescentic, or sickle, shape.

  • Sickling of red cells is initially reversible upon reoxygenation;Membrane damage occurs with each episode of sickling, and eventually the cells accumulate calcium, lose potassium and water, and become irreversibly sickled.

  • The presnce of HBS responsible for the clinical manifestationsChronic hemolysis.Microvascular occlusion,Tissue damage

  • sickle cell traitIn Heterozygote ie in sickle cell traitThe HbS is 40% and HbA is 60%.The remaining is HbA which in turn prevent HbS polymerization, so sickling is very unlikely.Only in profound Hypoxic condition it can cause anemia.

  • Why children remain asymptomatic till 5 to 6 months? Hereditary persistence of HbF in these people the sickle cell disease is less severe.Another variant Hb C Lysine is substituted for glutamate.

  • HbF also prevents the HbS polymerization so they remain asymptomaticIn some children th HbF remain higher level and sickling is very less.But HbC which causes the increase in the HbS and polymerization

  • MCHC levelsIncrease in the MCHC also increase the sicklingIntracellular PHDecrease in Ph facilitates the sicklingTransit time of red cells through microvascular beds.

  • Major consequences stem from the sickling of red cells chronic extravascular hemolytic anemiamicrovascular obstructionsresult in ischemic tissue damage and pain crises

  • PATHOGENESIS OF MICROVASCULAR OcclusionMicrovascular occlusion depends on red cell membrane damage and factors like Inflammation tend to slow or arrest rbcs movement thr microvaculature.Sickle cells exhibit high adhesion moledules and are sticky.The stagnation of rbcs causes Obstruction,hypoxia and more sickling.


    Depletion of NO occurs as released Hb from sickled rbcs bind to the NO and NO level decreases causes more narrowing of vessels platelet aggregation, red cell stasis and thrombosis.

  • Clinical findings

    Clinical findings Dactylitis (hand-foot syndrome)Painful swelling of hands and feet2. Acute chest syndromeBy chest infections esp sterp pneumonia and Fat emboli3. central nervous system stroke,

  • DactilitisDactylitis Hand Foot Syndrome Images- Image Results

  • Sickle cell anemia

  • Acute chest syndrome and stroke are the two leading causes of ischemia-related death4. aplastic crisisThere is transient decrease in erythropoisisDue to infection by parvovirus and leads to anemia5.Spenic sequestration crisisThere is massive entrapment of sickled cells into spleen leading splenic enlargement.

  • Hypovolemia and shock and sometime to death. 6.AutospleneetomySpleen enlarges to certain extent in childhood Spleen is fibrosed and diminish in size called auto spenectomy7,Vasoocclusive crisis also called pain crisis

  • Due to hypoxia and infarction cause severe pain AcidosisInfections and dehydration can trigger the pain crisisMore susceptible to infections by Salmonella,Strp pneumonia and H influenza.

  • Laboratory findingsHb electrophoresisDemonstrate HbSFetal DNA analysis by amniocentesisPeripheral blood findingsthere are sickle cells and targel cells.Hb concentration decreased.

  • Treatment and PrognosisHydroxyurea has beneficiary effectIt increases the HbF levelIt has anti-inflammatory effectAlso long term use of folic acidVaccination against H influenza and Sterptococcal. P

  • IMMUNE HEMOLYTIC ANEMIA General principalsAll require antigen-antibody reactionsTypes of reactions dependent on:Class of AntibodyNumber & Spacing of antigenic sites on cellAvailability of complementEnvironmental TemperatureFunctional status of reticuloendothelial systemManifestationsIntravascular hemolysisExtravascular hemolysis

  • Antibodies combine with RBC, & eitherActivate complement cascade, &/orOpsonize RBC for immune systemIf 1, if all of complement cascade is fixed to red cell, intravascular cell lysis occursIf 2, &/or if complement is only partially fixed, macrophages recognize Fc receptor of Ig &/or C3b of complement & phagocytize RBC, causing extravascular RBC destruction.

  • Immune Hemolytic anemiaImmune Hemolytic anemiaCaused by antibodies that bind to RBC leading to premature destructionCalled autoimmune hemolytic anemiaBut it triggered by ingestion of drugs so called Immune Hemolytic Anemia.

  • Two types of IHAWarm antibody type Cold antibody (agglutinin) type

  • Warm IHAIt is more common in women than menAlso in patients with SLEDrug induced methyldopa, penicillin,quinidine

  • Warm antibody type is more common (48% to 70%)and are of primary or idiopathic(50%)Secondary to SLE, Lymphomas,leukemias and other malignancy.

  • Most causative antibody is IgG IgG and sometime IgA antibodies are presentThe IgG coated red cell binds to fc receptors of phagocytes which remove red cell membrane causing spherocytosis cause splenomegaly.

  • Immune Complex MechanismQuinidine, Quinine, IsoniazidHaptenic Immune MechanismPenicillins, CephalosporinsTrue Autoimmune MechanismMethyldopa, L-DOPA, Procaineamide, Ibuprofen

  • Warm antibody IHAUsually IgG antibodiesFix complement only to level of C3,if at allImmunoglobulin binding occurs at all tempsFc receptors/C3b recognized by macrophages; Hemolysis primarily extravascular70% associated with other illnessesResponsive to steroids/splenectomy

  • HAPTEN MECHANSIMDrug binds to & reacts with red cell surface proteinsAntibodies recognize altered protein, drug, as foreignAntibodies bind to altered protein & initiate process leading to hemolysis

  • Auto antibody modelAlpha Methyl dopa an antihypertensive drug.This drug ini...


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