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HEM_ANEMIA_1.ppt
- 1. HEMOLYTIC ANEMIA Hemolytic anemia= reduced red-cell life span By Dr Abeer ELHadidi Ass.Prof of Clinical Pathology
- 2. Hemolytic anemia • Decreasedlevels of erythrocytes in circulating blood (anemia) because of their acclerated destruction (hemolysis) • A red blood cell survives 90 to 120 days (on average) in the circulation, therefore about 1% of human red blood cells break down each day.
- 3. • The spleen(part of the reticulo-endothelial system) is the main organ which removes old and damaged RBCs from the circulation. • In health, the breakdown and removal of RBCs from the circulation is matched by the production of new RBCs in the bone marrow.
- 4. • When therate of breakdown increases, the body compensates by producing more RBCs, but if compensation is inadequate clinical problems can appear and so anemia can develop.
- 5. • The breakdownproducts of hemoglobin will accumulate in the blood causing jaundice and be excreted in the urine causing the urine to become dark brown in colour.
- 6. Signs of hemolyticanemia: History • Onset/ duration (hereditary versus acquired) • History of fatigue or jaundice • Abdomen pain (chronic hemolysis) • Medications or food /ie fava bean/(may exacerbate enzyme deficiencies)
- 7. • Travel (considerinfection) • Blood loss or sequestration (increases reticulocytes in the absence of hemolysis) • Discolored urine (intravascular haemolysis) • Complete family history (jaundice, gallbladder disease, splenectomy)
- 8. Signs of hemolyticanemia: Physical • Symptoms of anemia • Jaundice • Pallor • Splenomegaly / hepatosplenomegaly
- 9. Laboratory findings: Peripheral bloodsmear microscopy: • Fragments of the red blood cells ("schistocytes") can be present • Spherocytes • Increased reticulocytes • Normoblasts can be present. • The level of unconjugated bilirubin in the blood is elevated. • The level of lactate dehydrogenase (LDH) in the blood is elevated
- 10. Laboratory findings(2) • Haptoglobin,hemopexin levels are decreased • Iron level in the blood is elevated. • The direct Coombs test is positive, if hemolysis is caused by an immune process. • Free hemoglobin, methemalbumin elevated level in the blood. • hemosiderin in the urine indicates chronic intravascular hemolysis.
- 11. Classification of hemolyticanemias •Causes of hemolytic anemis can be either genetic or acquired.
- 12. Classification of hemolyticanemia ===Genetic=== Genetic conditions of RBC membrane • Hereditary spherocytosis • Hereditary elliptocytosis Genetic conditions of RBC metabolism (enzyme defects) • G-6-P-D def • Pyruvate kinase deficiency Genetic conditions of hemoglobin • Sickle cell anemia • Thalassaemia
- 13. Classification of hemolyticanemias ===Acquired=== • ''Immune mediated hemolytic anemia''' (direct Coombs test is positive) Autoimmune hemolytic anemia • Warm antibody autoimmune hemolytic anemia (Ab binds at 37degree Celsius) ▫ Idiopathic ▫ Systemic lupus erythematosus (SLE) ▫ Evans' syndrome (antiplatelet antibodies and hemolytic antibodies)
- 14. • Cold antibodyautoimmune hemolytic anemia (Ab binds at 4degree Celsius) ▫ Idiopathic cold hemagglutinin syndrome ▫ Infectious mononucleosis and mycoplasma ( atypical) pneumonia ▫ Paroxysmal cold hemoglobinuria. (Rare cause seen in children in association with cong syphilis)
- 15. Classification of hemolyticanemia ===Acquired=== ' • Alloimmune hemolytic anemia • Hemolytic disease of the newborn (HDN) ▫ Rh disease (Rh D) ▫ ABO hemolytic disease of the newborn ▫ Anti-Kell hemolytic disease of the newborn ▫ Rhesus c hemolytic disease of the newborn ▫ Other blood group incompatibility (RhC, Rhe, RhE, Kidd antigen system, Duffy antigen, MN, P and others)
- 16. • Alloimmune hemolyticblood transfusion reactions (ie from a non-compatible blood type) • Drug induced immune mediated hemolytic anemia • Penicillin (high dose) • Methyldopa
- 17. Coombs Test • Typicalscreening is with broad spectrum reagent. • Contains antibodies directed at both human immunoglobulin and complement components
- 19. Direct Coomb’s test IndirectCoomb’s test
- 20. Classification of hemolyticanemia ===Acquired=== • Drugs (i.e., some drugs lead to hemolysis by direct action on RBCs) • Toxins (e.g., snake venom) • Trauma Mechanical (heart valves, extensive vascular surgery, microvascular disease) • Microangiopathic hemolytic anemia (e.g. TTP, HUS, DIC)
- 21. • Infections, Malaria(F. malaria: intravascular hemolysis: severe called ‘Blackwater fever), Babesiosis, Septicaemia • Membrane disorders Paroxysmal nocturnal hemoglobinuria (rare acquired clonal disorder of red blood cell surface proteins) Liver disease • Hypersplenism
- 22.
- 23. Mechanisms of hemolysis: -Intravascular - extravascular
- 24. Intravascular hemolysis : -red cells destruction occurs in vascular space - Clinical states associated with Intravascular hemolysis: 1)acute hemolytic transfusion reactions 2)severe and extensive burns 3)paroxysmal nocturnal hemoglobinuria 4)severe microangiopathic hemolysis 5)physical trauma 6)bacterial infections and parasitic infections (sepsis)
- 25. Intravascular hemolysis - laboratorysigns of intravascular hemolysis: tests for hemolysis and additionally: hemoglobinemia methemalbuminemia hemoglobinuria hemosiderinuria
- 27. Extravascular hemolysis : -red cells destruction occurs in reticuloendothelial system - clinical states associated with extravascular hemolysis: autoimmune hemolysis delayed hemolytic transfusion reactions hemoglobinopathies hereditary spherocytosis hypersplenism hemolysis with liver disease
- 29. Lab Findings inExtravascular Hemolysis: • Anemia • Unconjugated hyperbilirubinemia • Increased reticulocytes • Decreased haptoglobin • Increased urobilinogen
- 30. Laboratory Evaluation ofHemolysis Extravascular Intravascular HEMATOLOGIC Routine blood film Reticulocyte count Bone marrow examination Polychromatophilia Erythroid hyperplasia Polychromatophilia Erythroid hyperplasia PLASMA OR SERUM Bilirubin Haptoglobin Plasma hemoglobin Lactate dehydrogenase Unconjugated , Absent N/ (Variable) Unconjugated Absent (Variable) URINE Bilirubin Hemosiderin Hemoglobin 0 0 0 0 + + severe cases
- 31.
- 32. Hemolytic anemia (complications) •Clinical course may be complicated with Crisis: ▫ Hemolytic Crisis: associated with infection ▫ Aplastic crisis: associated with Parvovirus infection
- 33. Differential diagnosis * ''Ineffectivehematopoiesis'' is sometimes misdiagnosed as hemolysis. • Clinically these conditions may share many features of hemolysis • Red cell breakdown occurs before a fully developed red cell is released into the circulation. • Examples: myelodysplastic syndrome, megaloblastic anemia.
- 34. Hereditary Spherocytosis 1. Inheritedas autosomal dominant 2. red cell membrane protein defects (Deficiency of Beta Spectrin or Ankyrin) 3. Family history 4. Clinical features: jaundice, gallstones, splenomegaly.
- 35. • 5. Laboratoryfeatures - hemolytic anemia - microspherocytes - abnormal osmotic fragility test - negative direct Coombs test - increased MCHC
- 38.
- 39. Hereditary Elliptocytosis • EquatorialAfrica, SE Asia • AD / AR • Functional abnormality in one or more anchor proteins in RBC membrane- Alpha spectrin , Protein 4.1 • Usually asymptomatic • Mx: Similar to H. spherocytosis • Variant: 3.SE-Asian ovalocytosis: Common in Malaysia , Indonesia… Asymptomatic-usually Cells oval , rigid ,resist invasion by malarial parasites
- 40.
- 41. SICKLE CELL ANEMIA Definition:chronic hemolytic anemia characterized by sickle-shaped red cells(RBCs) caused by homozygous inheritance of Hemoglobin S
- 42. SICKLE CELL ANEMIA-pathogenesis -In HbS, valine is substituted for glutamic acid in the sixth amino acid of the ß chain. - Deoxy-HbS is much less soluble than deoxy HbA; it forms a gelatinous network of fibrous polymers that cause RBCs to sickle at sites of low pO2. - Hemolysis - because sickle RBCs are too fragile to withstand the mechanical trauma of circulation - Occlusion in microvascular circulation caused by distorted, inflexible RBCs adhering to vascular endothelium
- 43. SICKLE CELL ANEMIA-incidence -Homozygous - about 0.3% of blacks in the USA (have sickle cell anemia) - Heterozygotes 8-13% of blacks, (are not anemic, but the sickling can be demonstrated in vitro)
- 44. SICKLE CELL ANEMIA-clinicalfeatures IN HOMOZYGOTES 1. Clinical complications due to severe hemolytic anaemia - slow growth and development in children - gall bladder stones - aplastic crisis - congestive heart failure from chronic anemia and cardiac overload compensation 2. Consequences of vaso-occlusion of the microcirculations (tissue ischemia and infarction) - infarction of spleen, brain, kidney, lung, aseptic necrosis, central nervous system and ophtalmic vascular lesions
- 45. SICKLE CELL ANEMIA laboratoryfindinges 1. Anemia-normocytic or slightly macrocytic 2. Leukocytosis (chronic neutrophilia) 3. Thrombocytosis - usually mild 4. Reticulocytosis 5. Peripheral smear: sickle shaped red cells, polychromatophilia, Howell-Jolly bodies 6. Hb –electrophoresis or high-performance liquid chromatography (HPLC)
- 46. Sickle Cell Disease •Mutation in beta globin (6 Glu Val) • Inherited as autosomal recessive • Protection against malaria
- 47. Thalasemias • Thalasemia resultfrom gene (located on chromosomes 11 and 16) deletion, abnormalities in transcription and translation and instability of the mRNA directing globin synthesis or of the globin itself. • Result: imbalanced synthesis of normal globin chain. The unpaired chain accumulates in the developing erythroid precursor cell, and toxicity results – ineffective erythropoiesis, hemolysis and anemia of variable degree.
- 48. Thalassemia: Impaired Globin GeneProduction globin globin globin globin Hgb A tetramer
- 49. Different forms ofthalassemia • α thalassemia • β thalasemia: major, minor (trait), intermedia • δ/β thalassemia • Hereditary persistentce of fetal hemoglobin (HPFH)
- 50. Hemoglobin Chains Hgb(g/dl) MCV (fl) Analysis / Normal Normal Normal /- 12-14 75-85 Normal -/- or 11-13 70-75 Normal with Hgb Barts (4); --/ Hgb H (4) --/- 7-10 50-60 Normal with Hgb Barts (4); Hgb H (4) --/-- - - Not viable Alpha Thalassemia: Laboratory Findings
- 51. Beta Thalassemia Clinical Hgb SyndromeGenotype Hgb (g/dl) Analysi Minor (Trait) /+ or /° 10-13 Hgb A2, Hgb F Intermedia + /+ 7-9 Hgb A2, Hgb F Major(Cooleys) + /° or °/° < 7 Hgb A2, Hgb F
- 52. Beta-Thalassemia major (Cooley anemia) •Usually homozygous condition • Is the most severe variant no beta-chains are synthesized • Clinical features: severe anemia that appears in the first year of life; jaundice, hepatosplenomegaly (secondary neutropenia and thrombocytopenia), • skin pigmentation and chronic leg ulceration, • expansions of the erythroid marrow with secondary body changes (including retarded growth, bossing of skull, expanded maxilla, widened diploe, • gross skeletal deformities, spontaneous fractures, dental problem), increased susceptibility to infection, symptoms of iron overloading
- 53. Beta-Thalassemia major laboratory features •Severe anemia • Blood film: anisopoikilocytosis, hypochromia, target cells, basophilic stippling, reticulocytosis • Bone marrow: marked erythroid hyperplasia, increased sideroblasts • Shortened red cell survival • Fetal hemoglobin > 90%, HbA absent, HbA2 low/normal/high
- 54. Red Cell Enzymopathies 1.Glucose-6-Phosphate Dehydrogenase ( G6PD ) Deficiency ▫ Pivotal enzyme in HMP Shunt & produces NADPH to protect RBC against oxidative stress ▫ Most common enzymopathy -10% world’s population ▫ Protection against Malaria ▫ X-linked
- 55. • Clinical Features: ▫Acute drug induced hemolysis: Aspirin, primaquine, quinine, chloroquine, dapsone…. ▫ Chronic compensated hemolysis ▫ Infection/acute illness ▫ Neonatal jaundice ▫ Favism
- 56. • Investigation: ▫ e/onon-spherocytic intravascular hemolyis ▫ P. Smear: Bite cells, blister cells, irregular small cells, Heinz bodies, polychromasia ▫ G-6-PD level • Treatment: ▫ Stop the precipitating drug or treat the infection ▫ Acute transfusions if required
- 57. 2. Pyruvate KinaseDeficiency ▫ AR ▫ Deficient ATP production, Chronic hemolytic anemia • Investigation: P. Smear: Prickle cells Decreased enzyme activity ▫ Treatment: Transfusion may be required
- 58. Features of HEMOLYSIS Bilirubin LDH Reticulocytes,n-RBC Haptoglobulins +ve Urinary hemosiderin, Urobilinogen Blood Film Spherocytes No spherocytes Fragmentation DCT +ve DCT –ve Hereditery enzymopathies AI Hemolysis H. Sherocytosis Malaria, Clostidium Microangiopathic, Traumatic