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Toronto Notes 2019 Hemolytic Anemia Thalassemia
Definition
• defectsinproductionoftheαorβchainsofhemoglobin
■ resultingimbalanceinglobinchainsleadstoineffectiveerythropoiesisandhemolysisinthespleenorBM
• clinicalmanifestationsandtreatmentdependsonspecificgeneandnumberofallelesaffected • commonfeatures
■ increasing severity with increasing number of alleles involved ■ hypochromic microcytic anemia
■ basophilic stippling, abnormally shaped RBCs on blood film
Pathophysiology
• defectmaybeinanyoftheHbgenes
■ normally 4α genes in total; 2 on each copy of chromosome 16
■ normally 2β genes in total; 1 on each copy of chromosome 11
■ fetalhemoglobin,HbF(α2γ2),switchestoadultformsHbA(α2β2)andHbA2(α2δ2)at3-6mooflife ■ HbA constitutes 97% of adult hemoglobin
■ HbA2 constitutes 3% of adult hemoglobin
β-Thalassemia Minor (Thalassemia Trait)
Definition
• defectinsinglealleleofβgene(heterozygousforonenormalβglobinalleleandoneβglobin thalassemic allele)
• commoninpeopleofMediterraneanandAsiandescent
Clinical Features
• usuallyasymptomatic;apalpablespleenisveryrare
Investigations
• Hb(100-140g/L),MCV(<70fL),Fe(normal),RBCcount(normal) • peripheralbloodfilm–microcytosisbasophilicstippling
• Hbelectrophoresis
■ specific: HbA2 increased to 3.5-5% (normal 1.5-3.5%) ■ non-specific: 50% have slight increase in HbF
Treatment
• notreatmentrequired
• geneticcounsellingforpatientandfamily
β-Thalassemia Major Definition
• defectinbothallelesofβgene(homozygous,autosomalrecessive)
Pathophysiology
• ineffectivechainsynthesisleadingtoineffectiveerythropoiesis,hemolysisofRBCs,andincreaseinHbF
Clinical Features
• initialpresentationatage6-12mowhenHbA(α2/β2)normallyreplacesHbF(α2/γ2) ■ severe anemia, jaundice
• ironoverloadduetocompensatorygastrointestinalironuptakeprogressingtohemochromatosis ■ secondary to repeated transfusions and ineffective erythropoiesis
■ leads to iron-induced organ damage
• stunted growth and development (hypogonadal dwarf )
• grosshepatosplenomegaly(duetoextramedullaryhematopoiesis)
• radiologicchanges(duetoexpandedmarrowcavity)andextramedullaryhematopoieticmasses
(erythroid tissue tumours)
■ skull x-ray has “hair-on-end” appearance ■ pathologic fractures common
• evidenceofincreasedHbcatabolism(e.g.pigmentedgallstones)
• deathcanresultfrom:
■ untreated anemia (should transfuse)
■ infection (should identify and treat early)
■ iron overload (common): late complication from repeated transfusions and ineffective
erythropoiesis
Investigations
• severemicrocyticanemia(Hb<60g/L)
• peripheralbloodfilm:teardrop,target,hypochromatic,microcytic • Hbelectrophoresis
■ HbA: 0-10% (normal >95%) ■ HbA2 >2.5%
■ HbF: 90-100%
Hematology H19
Microcytosis in β-Thal Minor Microcytosis is much more profound and the anemia is much milder than that of iron deficiency
Hemochromatosis Clinical Features
ABCDH
Arthralgia
Bronze skin
Cardiomyopathy, cirrhosis of liver Diabetes (pancreatic damage) Hypogonadism (anterior pituitary damage)