Date post: | 31-May-2015 |
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Health & Medicine |
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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!