HAEMOLYTIC ANEMIADefinition: anaemia that arised due to increase destruction of erythrocyteClassification:INTRACORPUSCULAR HEMOLYSISMembrane Abnormalities (Spherocytosis)Haemoglobin defects (Thalassemia, Sickle cell Anaemia)Enzyme defects (G6PD Deficiency)EXTRACORPUSCULAR HEMOLYSISNonimmune (Drug related, Mechanical)Immune (Autoimmune, Alloimmune)
HEREDITARY SPHEROCYTOSIS -
EPIDEMIOLOGY1:5000 in CaucasiansIts inheritance, often autosomal dominant (), and autosomal recessive ()Maybe no FHx, caused by new mutationNorthen europe are most common but also in SE Asia
ETIOLOGY AND PATHOGENESISMutation in the genes for protein of RBC membrane (spectrin, ankyrin or band 3)Producing spheroidal shaped and osmotically fragile RBCs that are trapped and destroyed in the spleen, resulting in shortened RBC lifespan.
Clinical FeaturesAnaemia (Hb=9-11g/dl, transiently fall during infection) Intermittent jaundice (severe: in 1st few day of life/childhood) Splenomegaly Haemolytic crises (hemolysis)Pigmented gallstones in adolescents and young adults due to increased bilirubin excretionAplastic crises (reticulocytopenia) with Parvovirus B19 infections (2-4 weeks) Megaloblastic crises
COMPLICATIONGout, Leg ulcersChronic erythematous dermatitis of legsExtramedullary hematopoesisHematologic malignancies : multiple myeloma, leukemia, hepatomaHeart disease: CCF, cardiomyopathy
TREATMENTIf Hb > 10 gm/dl and retics < 10%- no RxIf severe anemia, poor growth, aplastic crises and age 10 % or massive spleen- splenectomy Folic acid- 1 mg/day (mild)** SplenotomyTo be delayed as long as possibleMild cases: no need, unless gallstone developedAvoided for patients < 5 years age because of the increased risk of postsplenectomy sepsisGive pneumococcal, haemophilus and meningococcal vaccination 4-6 weeks prior to splenectomy and prophylactic oral penicillin to be given post-splenectomy.
INTRODUCTIONInherited blood disorder presenting with anaemia at 4 - 6 months of ageCommon presenting symptoms are pallor, lethargy, failure to thrive and hepatosplenomegalyMost often in Indian subcontinent, Mediterranean, and middle EastIn Malaysia, the -thalassaemia carrier rate is estimated at 3-5%, most of whom are unaware of their carrier / thalassaemia minor status. Must perform prenatal dx: DNA analysis of chorionic villius sample
-ThalassemiaTypes:Beta-Thalassemia major (o/o genotype): most severe form, HbA (22) cannot be produced because of the abnormal globin gene. Beta- Thalssemia intermedia(+/o or +/+ genotype): milder, varies severity; beta globulin allow small HbA or large amount of HbF to be producedBeta Thalassemia minor(/o or /+ genotype): Only one of the two globin alleles contains a mutation, so chain production is not terribly compromised and patients may be relatively asymptomatic.
SxSevere anemia, transfusion dependent, 4-6months of life, a/w jaundiceGrowth failureExtramedullary hemopoiesis (Hepatosplenomegaly, bone marrow expansion)Management:Lifelong monthly bld transfusionIron chelation for repeated bld transfusion (desferrioxamine)Bone marrow transplantation
Bld transfusion to maintain Hb conc. >10g/dl, reduce growth failure and prevent bone deformationRepeated bld transfusion cause iron oveload and with cx of HF, liver cirrhosis,DM, infertility and growth failureDesferrioxamine: subcutaneus or oral (2-3y/o)
Sickle Cell Anaemia
PathogenesisHbS form due to mutation in beta globulin geneChanges in AA encoded frm glutamine to valine
Clinical manifestationAnaemia: Hb=6-10g/dl with jaundice frm chronic hemolysisInfection (due to hyposplenism)Painful crises: vaso-occlusive crises lead to pain ( dactylitis)Hemolytic, aplastic,sequestration crisesPriapism: might cause copora carvenosa fibrosis and subsequent erectile incompetenceSplenomegalyLong term problems: gallstone, renal failure, cardiac elargement, delayed puberty and short stature, adenotonsillar hypertrophy, leg ulcer, stroke and cognitive problems
Avascular necrosisis the death of bone tissue due to a lack of blood supply. Also called osteonecrosis,avascular necrosiscan lead to tiny breaks in the bone and the bone's eventual collapse.
DiagnosisElectrophoresis: polymerization of HbSCBC: decrease Hb, ESR; leucocytosis, thrombocytosis, reticulocytosisBlood smear: sickle shape RBCIncrease in serum bilirubin
TreatmentAcute crisesOral/ IV analgesia- pain crisesAntibiotics- InfectionExchange transfusion- indicated for acute chest syndrome, stroke and priapismChronic problemHydroxyurea: recurrent admission with pain crises and acute chest syndromeBone marrow transplant (frm HLA identical sibling)
Glucose-6-Phosphate Dehydrogenase (G6PD) Defeciency -6-
IntroductionG6PD- essential for pentose oxidative pathway and prevent oxidative damage to RBCLacking cause oxidant induced hemolysisX linked recessive, predominantly in malesHeterozygous female: normal; affected only when female are homozygous
Clinical Manifestation:Neonatal jaundice: onset on 1st 3 day of lifeAcute hemolysis- precipitated by:Infection (pnemonia, hepatitis, typhoid feverCertain drugs ( antimalaria, antibiotics,analgesics-aspirin and chemicals)Fava beansNapthalene in mothballDiagnosis:Enzyme increase during hemolytic crisesReticulocytosisIncrease conjugated and unconjugated bilirubin,LDH, alkaline phosphateTreatment:Parents given list of drugs, food and chemical to avoidRerely use transfusion
Autoimmune hemolytic anemia
Diagnosis and TreatmentDiagnosis:Biochemical analysis: increase LDH, unconjugated bilirubin; decreased serum ironUrine: hemosiderinuriaDirect Coomb Test -ve
Treatment:Treating underlying dzPlasmapheresisIV IgApoptotic inhibitor