CLASSIFICATION OF ANAEMIAS:Morphological

SizeShapeColour

Pathogeneticblood lossReduced productionincreased destruction

HAEMOPOIETIC SYSTEM

Morphological classification:1. Normocytic Normochromic

blood lossaplastic anaemiaACDhemolytic anameia

HAEMOPOIETIC SYSTEM

2. Microcytic HypochromicIron deficiency anaemiaThalassaemiasSidroblastic anaemiaACD

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3. MacrocyticMegaloblastic anaemiahemolytic anaemia

HAEMOPOIETIC SYSTEM

Pathogenetic classification:1. Blood loss

AcuteChronic

2. Increased destruction (hemolytic)Hereditary

membrane defectsSpherocytosisElliptocytosis

HAEMOPOIETIC SYSTEM

Metabolic defectsG6PD deficiencyPK deficiency

Hb defectsquantitaive defects

Thalassaemiasqualitative defects

sickle cell anaemiaHbC, D, Eunstable Hb

HAEMOPOIETIC SYSTEM

AcquiredImmune hemolytic anaemiasNon immune

MAHAs (mechanical)PNHmalaria & other infectionsmechanical trauma

HypersplenismDICDrugs

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3. Impaired production:Nutritional deficiencies

megaloblastic anaemiairon deficiency anaemia

Aplastic anaemiaPure red cell aplasiasideroblastic anaemiaanaemia of chronic disease

HAEMOPOIETIC SYSTEM

HAEMOPOIETIC SYSTEM

Parameter Males Females

Hb 15+/-2 gm/dl 13+/-1.5

RBC count 5+/-0.5x1012/l 4.5+/-0.5

PCV 0.45+/- 0.05l/l 0.4+/- 0.5 l/l

MCV 92 +/- 9 fl

MCH 29.5+/-2.5 pg

MCHC 33 +/- 1.5 g/dl

Cell diameter 6.7 – 7.7 um

Reticulocyte count

0.5-2.5%50 – 100x1012/l

HEMOLYTIC ANAEMIAS:Normal red cell life span = 120 days

Splenic reticuloendothelial cells

Degradation of Hb bilirubin

HAEMOPOIETIC SYSTEM

Hemolysis shortened red cell life span

Stimulated erythropoiesis intra &extramedullary

↑ Hb breakdown ↑ bilirubin jaundice gall stones

HAEMOPOIETIC SYSTEM

HAEMOPOIETIC SYSTEM

Extravascular IntravascularPhysiologic PathologicRE cells spleen In blood vesselsFc receptor mediated Complement mediatedLess deformable RBC Mechanical injurySplenomegaly ++ Splenomegaly +/-Indirect hyperbilirubinaemia

Hbaemia, Hburia, hemosidrinuria

Janudice ++ Jandice +

Normal ↓ plasma Haptoglobin

Anaemia ↑ EPO erythroid hyperplasia Marrow expansion reticulocytosis

Leukoerythroblastic blood picture Gall stones haemosiderosis

HAEMOPOIETIC SYSTEM

Never look down on anybody unless you're helping him up

HEREDITARYSPHEROCYTOSIS:

HAEMOPOIETIC SYSTEM

Autosomal dominantIntrinsic membrane defectDeformability of RBC due to cytoskeletalProteinsSpectrinActinAnkyrinBand 4.2 & 3

HAEMOPOIETIC SYSTEM

Reduced membrane stabilityReduced deformability spheroidalTrapped in spleen lactic acid ++Intracellular Na+ ↑ osmotic injury Phagocytosis by RE cellsSplenomegaly

HAEMOPOIETIC SYSTEM

Variable severityChronic hemolytic anaemiaAplastic crisisHemolytic crisis

HAEMOPOIETIC SYSTEM

DIAGNOSIS:HistoryExaminationBlood filmOsmotic Fragility test

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GLUCOSE 6 PO4 DEHYDROGENASEDEFICIENCY

HAEMOPOIETIC SYSTEM

X linkedOxidant damage to RBCs Heinz bodies Bite cellsOxidant stress:

Drugs (antimalarials, sulfonamides)Foods (Fava beans)Infections

HAEMOPOIETIC SYSTEM

Variants G6PD-A (Mediterranian) G6PD-B (commonest) G6PD A- (African, mild)

Neonatal jaundiceAcute hemolysisChronic low grade hemolysis

Intravascular hemolysisExtravascular hemolysis

HAEMOPOIETIC SYSTEM

5 years boyProgressive pallorPainful swelling of fingers & toesJaundice twiceO/E pallor ++Jaundice +Spleen +Leg ulcersShort right middle finger

HAEMOPOIETIC SYSTEM

Hb = 5.5 gm/dlMCV = 74 flMCH = 26 l/lTLC = 18.6Plt = 110Retics = 12 %Leucoerythroblastic blood picture

HAEMOPOIETIC SYSTEM

HAEMOGLOBIN ELECTROPHORESIS:

Band of HbS

HAEMOPOIETIC SYSTEM

SICKLING TEST

HAEMOPOIETIC SYSTEM

SICKLE CELL DISEASE:Autosomal recessiveStructural variant of Hb

6th position β globin chainValine Glutamic acid HbS

HAEMOPOIETIC SYSTEM

Deoxy Hb↓

Crystallization/polymerization HbS↓

Tactoid formation (reversible)↓

Repeated sickling de-sickling↓

Irreversibly sickled↓

Vascular occlusion

HAEMOPOIETIC SYSTEM

Membrane damage ↑ Ca ↓ K+↓

Intracellular dehydration↓

Sticky RBCs↓

Vascular occlusion

HAEMOPOIETIC SYSTEM

Homozygous SCDHeterozygous SC traitHbF inhibits polymerization of HbSIntracellular dehydration ↑ MCHC

Sickling ++↓ pH deoxy Hb sickling

HAEMOPOIETIC SYSTEM

CLINICAL PRESENTATION:Chronic hemolysis (extravascular)AnaemiaJaundiceInfections by encapsulated organismsosteomyelitis (salmonella)H-Influenza, PneumococciLeg ulcers

HAEMOPOIETIC SYSTEM

Vaso occlusive crisis painful crisisbones hand – foot syndrome lungs acute chest syndromebrain seizures / strokeliver hepatic sequestration painspleen sequestration syndromepenis

HAEMOPOIETIC SYSTEM

Marrow expansion hair on ends (x-ray skull)

Prominent cheek bonesExtramedullary haemopoiesisGall stonesAplastic crisis (parvo virus)Autosplenetomy

HAEMOPOIETIC SYSTEM

DIAGNOSIS:HistoryExaminationPeripheral smear

ISCleucoerythroblastic blood picturereticulocytosis

HAEMOPOIETIC SYSTEM

Hb electrophoresisHbS band

Sickling testPCR

HAEMOPOIETIC SYSTEM

MANAGEMENT:Blood transfusion (RCC)PreventionBone marrow transplant

HAEMOPOIETIC SYSTEM

A man who is "of sound mind" is one who keeps the inner madman under lock and key

HAEMOGLOBIN:Heme + 4 Globin chains

HbA 2a/2βHbA2 2a/2δHbF 2a/2γ

ξ and ζ embryonic chains

HAEMOPOIETIC SYSTEM

Synthesis of globin chains:Haemopoietic GF

↓Gene activation

↓Transcription

↓Translation

↓Post translation stability

HAEMOPOIETIC SYSTEM

1.5 year girlFailure to thrivepallor and abdominal distensionCousin died at 3 years with similar problemsOne transfusion 2 months back

O/E pallor +++Spleen 4 cmLiver edge

HAEMOPOIETIC SYSTEM

TLC : 24.6Hb : 6.2Plt : 130MCV : 72MCH : 21NRBC 43/100 WBCLeft shift in neutrophils

HAEMOPOIETIC SYSTEM

HbF : 97%

DIAGNOSIS:Clinical, blood and electrophoresis findings

are consistent with β - THALASSAEMIA MAJOR(β°)

HAEMOPOIETIC SYSTEM

THALASSAEMIAS:Reduced or no synthesis of one or moreglobin chains of Hb.Autosomal recessiveα chain deficiency α thalassaemiaβ chain deficiency β thalassaemia

HAEMOPOIETIC SYSTEM

CLASSIFICATION:ClinicalGeneticThalassaemia major

homozygous β + (β+/ β+)homozygous β o (βo / βo) β / Hb Lepore β / HbE

HAEMOPOIETIC SYSTEM

Thalassaemia Intermedia: β+/β+ β with α thalassaemiaHbH disease β/δ compound heterozygotesHbE/ β

HAEMOPOIETIC SYSTEM

Thalassaemia minor:Silent carriers

α + thalassaemia traitrare β thalassaemia trait

Mild anaemia α o thalassaemia trait α+/α+ thalassaemia β o trait β + trait δβ trait

HAEMOPOIETIC SYSTEM

BETA THALASSAEMIA:Mutations in β globin gene

Transcriptionpromoter region mutationschain terminator mutations

Processing of mRNAsplicing mutationssplice site in exonIVSCAP site

HAEMOPOIETIC SYSTEM

Translationnonsenseframeshiftinitiation site

Post translational stabilityExon 3

HAEMOPOIETIC SYSTEM

DIAGNOSIS:HistoryExaminationBlood filmHb electrophoresisPCRFamily studies

HAEMOPOIETIC SYSTEM

TREATMENT:Regular blood transfusionsIron chelation

injectableoral

Supportive treatmentBone marrow transplant

HAEMOPOIETIC SYSTEM

PREVENTION***genetic counselingantenatal diagnosis

COMPLICATIONS:growth retardationiron overload

endocrine abnormalitiesCCFhepatic failure

transfusion mediated infections (HBV,HCV)

HAEMOPOIETIC SYSTEM

"Sometimes the best helping hand you can get is a good, firm push”

ACQUIRED HEMOLYTIC ANAEMIAS:Immune hemolytic anaemia:Autoimmune HA

warm antibody typeidiopathicautoimmune diseasesLPDinfectionscancersdrugs

HAEMOPOIETIC SYSTEM

cold antibody typecold agglutinin syndromeCHAD (idiopathic)infectionsLPDPCH

HAEMOPOIETIC SYSTEM

Alloimmune HAtransfusion reactionsHDNallograft associateddrug induced

macrophage mediatedcomplement mediated

HAEMOPOIETIC SYSTEM

HAEMOPOIETIC SYSTEM

Warm antibody HA Cold antibody HA

Commonest (45-70%) 15-30%

50% idiopathic Secondary >

IgG, IgA IgM

Extravascular hemolysis

Intravascular ++Extravascular <

Fc receptor mediated mcrophage

Complement activation, C3b macro

HAEMOPOIETIC SYSTEM

Spherocytosis RBC agglutinates

Splenomegaly Raynauds phenomena

Paroxysmal Cold Haemoglobinuria:Acute intermittent severe intravascularHemolysisP blood groupDonath – Landsteiner antibodyIgG biphasic antibodyComplement mediated

HAEMOPOIETIC SYSTEM

35 yrs femaleMother of 5 children (LCB 1.5 yrs)H/O menorrhagia 1 yearIncreasing weakness & fatiguabilityHusband is a labourer

HAEMOPOIETIC SYSTEM

Blood CP:Hb : 7.6 gm/dlTLC : 6.5Plt : 460MCV : 66MCH : 19DLC : normalRetics 1.0 %

HAEMOPOIETIC SYSTEM

Serum iron: 23 ug/dl (60-180)TIBC : 650 ug/dl (250-400)Serum Ferritin 6 ng/ml (15-150)DIAGNOSIS:

IRON DEFICIENCY ANAEMIA.

HAEMOPOIETIC SYSTEM

IRON METABOLISM:Diet / sourceAbsorptionTransportUtilization & excretionStoragedeficiency

HAEMOPOIETIC SYSTEM

Iron conc in males = 50 mg/kg females = 40 mg/kg

Total body iron = 3-5 gm7-8 yrs for depletion6 months-2 yrs physiological iron def

HAEMOPOIETIC SYSTEM

HAEMOPOIETIC SYSTEM

Absorption increased absorption decreased

Heme iron, animal food Opposite

Ferrous salts Ferric salts

Acid gastric pH Alkalis

Vit C, amino acids, sugars Phytates, tannates, tea

Iron deficiency Iron overload

↑ eryhthropoiesis ↓ erythropoiesis

Pregnancy Inflammatory disorders

Hypoxia ------

Causes of iron deficiency:Dietary lack

povertyold agevegetarians

Increased demandpregnancy & lactationinfants & childrenpuberty

HAEMOPOIETIC SYSTEM

Impaired absorptionmalaborption syndromesachlorhydriagastrectomyatrophic gastritis

Chronic blood lossGIT, genitourinary, respiratoryhook worm infestation

HAEMOPOIETIC SYSTEM

Clinical presentation:symptoms of anaemiasymptoms related to cause

Examination:pallorangular cheilosiskoilonychia

Absence of certain features

HAEMOPOIETIC SYSTEM

Diagnosis:HistoryExaminationRoutine investigationsSerum ferritinSerum iron TIBCBone marrow examination.

HAEMOPOIETIC SYSTEM

Treatment:Treatment of causeIron supplements

oralinjectable

HAEMOPOIETIC SYSTEM

Ability is of little account without opportunity

MEGALOBLASTIC ANAEMIA:A group of disorders characterized bypresence of MEGALOBLASTS in the bonemarrow.Impaired DNA synthesis

HAEMOPOIETIC SYSTEM

Causes:Cobalamine deficiency or defect in metabolismFolate deficiency or defect in metabolismMDS, AMLAntifolate drugs, drugs interfering with DNA

synthesisOrotic aciduriaLesh-Nyhan syndrome

HAEMOPOIETIC SYSTEM

DNA synthesisRapidly proliferating cells

haemopoietic cells ….GIT ….

diarrhoea can be cause or effectGUT ….respiratory …..prematurityneural tube defects

HAEMOPOIETIC SYSTEM

Methylation of biogenic amines(dopamine)

psychitric symptomsOf myelin proteins, phospholipids

Neurologic symptomsbilateral peripheral neuropathydegeneration of dorsal columns &

pyramidal tractsoptic atrophymental abnormalities (poor brain dev)

HAEMOPOIETIC SYSTEM

Haematological findings:oval macrocytosisMCV > 100 flpancytopeniahypersegmented neutrophils

HAEMOPOIETIC SYSTEM

Bone marrow findings:HypercellularDyserythropoiesisIneffective erythropoiesisMegaloblastsGiant myeloid precursorsHyperlobated megakaryocytesAbnormal mitotic figures

HAEMOPOIETIC SYSTEM

MEGALOBLAST:

Large abnormal erythroid precursorsnuclear cytoplasmic asynchrony

COBALAMINE (VITAMIN B12)Only source animal foodBody stores = 2-3 mgSufficient for 3-4 yearsAbsorption (ileum, IF) Transport (transcobalamines)

HAEMOPOIETIC SYSTEM

Causes of Cobalamine deficiency:1. Vegans2. Malabsorption

Pernicious anaemiagastric causes

IF defgastrectomy

HAEMOPOIETIC SYSTEM

intestinal causesstagnant loop syndromesileal resectioncrohn’s diseasetropical spruefish tape wormsTC deficiency

HAEMOPOIETIC SYSTEM

PERNICIOUS ANAEMIASpecific type of MBASevere lack of Intrinsic factor due togastric atrophyAutoimmune disorderAnti IF antibodiesAnti Parietal cell antibodies

HAEMOPOIETIC SYSTEM

Diagnosis:HistoryExaminationBlood CPBone marrow examinationSerum B12 levelsSchillings testIF & PC antibodiesElevated homocystine & CH3-malonic acidTherapeutic response

HAEMOPOIETIC SYSTEM

FOLIC ACID (Pteroylglutamic acid)Liver, yeast, spinach, greens, nutsTotal store = 10 mgFor 4-6 monthsAbsorbed from upper small intestinePolyglutamates monoglutamatesTransported by albumin

HAEMOPOIETIC SYSTEM

Causes of deficiency:1. Dietary:

old age, poverty, infancy, alcoholism,psychiatrics

2. Malabsorptiontropical sprueceliac diseaseintestinal resectioncrohns disease

HAEMOPOIETIC SYSTEM

3. Excess demand:physiological

pregnancy, prematurity, lactationpathological

hemolytic anaemias, malignanciesinflammatory conditionshomocystinuriahemodialysis patients

HAEMOPOIETIC SYSTEM

4. Anti-folate drugs:anticonvulsantsantiTBtetracyclins

5. Liver disease, alcoholism

HAEMOPOIETIC SYSTEM

Treatment:1. Of cause2. Cobalamine injections3. Folic acid tablets

HAEMOPOIETIC SYSTEM

APLASTIC ANAEMIA:“Presence of pancytopenia in theperipheral blood & a hypocellularmarrow in which normal haemopoieticmarrow is replaced by fat cells.”

HAEMOPOIETIC SYSTEM

Haemopoietic stem cell defectDefect in microenvironmentCytotoxic T cell mediated suppression ofStem cellsIFN gamma, TNFAbsence of abnormal cells or fibrosis in Bone marrow

HAEMOPOIETIC SYSTEM

Causes:Idiopathic

primary stem cell defectimmune mediated

Chemical agentsdose related

alkylating agents & antimetabolitesbenzene, arsenicchloramphenicol

HAEMOPOIETIC SYSTEM

idiosyncraticchloramphenicolphenylbutazonearsenic, streptomycininsecticides & pesticides

Physical agentsradiation

HAEMOPOIETIC SYSTEM

InfectionshepatitisCMV, EBV, herpes V

InheritedFanconi’s anaemia

HAEMOPOIETIC SYSTEM

Clinical presentation:Anaemia Thrombocytopenia Neutropenia

HAEMOPOIETIC SYSTEM

Diagnosis:HistoryExaminationBlood CPBone marrow aspiration & trephine

HAEMOPOIETIC SYSTEM

The purpose of life is to live a life of purpose.