Hemolytic anaemias

DR.WACHIRA

DR.M.D.MAINA

defination

• Premature destruction of red blood cells anaemia results when destruction exceeds marrows response..

Hereditary spherocytosis

• Autosomal dominant..familial..esp northern europe.the molecular defect s are abnormalities in spectrin ot ankyrin.

• Can be assymptomatic or severe hemolysis• Causing increased permiability,decreased

deformability impaiting passage within spleen.• Resolved with splenectomy

Clinical features

• assymptomatic• Newborn:HdN • Anemia pallour,jaundice,exercise intolerance• Enlarged diploe• Gallstones• Aplastic crisis

IX

• Fhg pbf• Bilirubin• Osmotic fragility test• Retic count • Haptoglobulin• Bma• RX spleenomegaly

Hereditary elliptocytosis• Autosomal dominant• Rare.Found in west africa..• Ass with spectrin mutations-provides for

resistance to malaria infections.• Also caused by def in iron B12 and folic acid.• IX:pbf elongated rod likeRBC.microcytes

poikilocytes.• :erythroid hyperplasia on bma• RX:spleenomegaly if severe hemolysis

Other structural defects• Hereditary stomacytosis:cup shaped,,also

seen in liver disease.increased permeability to na+ k+spleenomegaly not recommended

• PNH:deficient pr on surface that renders rbc susceptible to complement.presents with thrombocytopenia leaucopenia headache backache.may progress to AML. Dxham test,flow cytometry

• Acanthocytosis irregular circumfrencial projections.seen with alterations in cholesterol/phospholip ratio..

PATHOPHYSIOLOGY

• Chroninc infl.• Cellular dehydration:membrane injury• Abnormal cell adhesiveness• Inflammation:no,mo,il 1 6 tnf alpha,adhesion

molecules• Activation of coagulation system• Ischaemia reperfusion injury

SCD• Valine for glutamine at 6th psn beta chain.so hb os

polymerised under certain conditions.rare newborn symptoms.

95%dactylitis frequently first presentation.ischaemic necrosis of small bones a predictor of severe of severe course also anemia and painful crises before 2years.

• mortality associate most with sepsis and ACS.noted altered splenic fxn phagocytic and rectiend. Reduced ability of alternate complement system

• Cva after 5years:trans cranial doppler ultrasound.occult in 25-30%

• Poor prognostic factors: anaemia ,freq vaso occlusive episodes ,dactylitis before 2years

• Children:extremeties adults:head,chest abd,back

• Hypersplenism in young children ass with worsening anaemia and thrombocytopenia

• Acute splenic sequestration:episode ass with pooling of blood in the spleen..circulatory collapse.transfusions life saving. Asplenia by 5years

• Avascular necrosis,cholelithiasis.salmonella osteoomyelitis.adolescentsincreased uti and priapism.PHTN 2 to frequent ACS.

• 12% Progressive impaired renal function with glo and tubular fibrosis.rarely nephrotic syndrome.

• IX:inc retic 5-15%,inc wbc,N mcv,anaemia. pbf:target cells,poikilocytes,sickled cells,howel jolly

bodies,sickled red cellsnucleated rbc.. Hyperplastic marrow. hbF 10-25%

SCTrait: HbAs lifespan normal.death due to splenic infarcts in high altitude,hematuria,bacteriuria.ass with renal medullary carcinoma

thalassemia classified major minor intermediate,trait reffering to

degree of anaemia Have shorter RBCspan,persistent fetal hb and rbcs are

sensitive to oxidative stress.alpha or beta are mostly deletions.main feature is globin chain imbalance.resultineffective erythropoiesis with hypereactive marrow but with few retics and severe anaemia.

• Clin.f progressive hemolytic anaemia with weakenss and cardiac failure(<4g/dl)

• Intermediate microcytic anemia hb 7• Triat frequently dx a IDA.increase HbF and HbA2

others

• Hemoglobin with high O2 affinity (110)• Hb C,D,E

ENZYME DEFECTS

pyruvate kinase def :autosomal recessive with marked reduction of pk or decreased activity.

Clin f vary from severe neonatal hemolytic anemia tomild hemolysis in adulthood..

Hb 8-12.,pallour,jaundiceIX: inc retic.

• G6p dh def: symp 24-48hours after exposure to oxidising agent…hemolysis is dependent on inciting agent,ammount ingested and degree of enzyme severity..

pbfshows fragmented cells and bluish large rbc’s (retic cells) heinz bodies

Fever,dizziness,confusion,weakness

How Drugs Affect G6PD Deficient Individuals?

GlucoseGlucose-6-phosphate

6-Phosphogluconate

Ribose-5-phosphate

Fructose-6-phosphate

Glyceraldehyde-3-phosphate+

Pent

ose

Shun

t

G6PDehydrogenase

NADPH

NADP+

GSSG

GSHGSH reductase

NADPH

NADP+

H2O

↑H2O2 O2

Catalase

NAD+

NADH

Fe2+ (oxyHb)

Fe3+

(metHb)

Drugs

Glyceraldehyde-3-phosphate

2 OH

Hemolysis

SuperoxideDesmutase(SOD)

(Fe2+)GSH Peroxidase

NADPH

(O2 )

Other extracellular factors• autoimmune hemolytic anemia: +ve direct

antiglobulin test (coombs)eg HDN,ass with infe esp ebv..ass with methyldopa,immunodef states

• Autoimmune h.a ass with warm a/bodies• Autoimmune h.a ass with cold a/bodies• Thermal injury• Renal disease• Liver disease• Wilsons disease

DANKE!