• acidosis
• 2,3 DPG
• increase P_CO2

• alkalosis

• alpha- 4 loci on chromosome 16
• beta- 2 loci on chromosome 11
• gamma- 2 loci on chromosome 11
• sigma- 2 loci on chromosome 11

• Hb A = alpha 2 and beta 2
• Hb A2 = alpha 2 and sigma 2

• alpha chains produced and continually produce
• gamma rapid rise in fist trimester, then steady decline until third trimester when it rapidly declines
• beta steadily increases, but has a substantial increase by 30 wks of gestation

• types
  • heterozygote- thal. minor
  • homozygote- thal. major
• consequences
  • decrease RBC Hb
  • increase free alpha chains (precipitate in RBC's)

• beta^o- no beta chains made due to total abolishion of expression of affected gene by critical point mutation
• beta⁺- partially abolish gene expression with mild, moderate, severe- depending on amount of HbA produce

• ineffective erythropoiesis
• hemolysis
• marrow expansion
• extramedullary hematopoiesis

epi- seen in Italians, Greeks, Arabs, Blacks

• signs/symp.
  • high output (CHF
  • severe anemia
  • chipmunk facies
  • extramedullary hematopoiesis
  • X ray show "hair on end"
• tx- transfusions early
• death via hemachromatosis

• beta⁺
• beta⁰
• delta, beta
• Hb leporae (no beta chain with delta chain replaced by delta beta hybrid
• hereditary persistance of HbF (HPFH)- no beta or delta chain, so defect fully compensated by increased gamma chain production

• transfusion by maintaining Hb around 9-10
• iron chelation to reduce liver Fe
• stem cell transplantation
• tx in comprehensive thalassemia center: endocrinology, cardiology, social services
• in selected populations, heterozygote screning and antenatal dx

• deferoxamine (most active, given bu slow IV infusion)
• deferasirox- QD, can remove cardiac Fe, but can increase creatinine and proteinuria (dosage adjust)
• deferiprone- efficacy as chelator less than other drugs, can remove cardiac Fe, use in combo with other drugs (greater toxicity)

• must not confuse with Fe deficiency anemia
• reticulocytosis
• anemia (MCV- 65)

• structure
  • two alpha, two gamma
  • two types of gamma chains: G and A
  • partly acetylated
• function
  • similar oxygen affinity to HbA
  • but, 2,3 DPG has little effect on oxygen binding

• Hb electrophoresis
  • alkaline cellulose acetate/starch
  • relies of differential migration

• decrease alpha syn.
• Hb electrophoresis NOT helpful
• excess of beta chains
• abnormal Hb formed
  • Hb barts: gamma 4 (holds on to oxygen so tight any Hb dies)
  • HbH: beta 4

• thal trait (1, 2 gens gone)- w/o symptoms, mild symptoms
  • 2 genes, with mild hypocromic anemia
• Hb H (3 genes nonfunctional)
  • unstable Hb
  • ineffective erythropoiesis
  • brisk hemolysis
• Hb barts hydrops fetalis
  • no alpha chains whatesoever
  • eclampsia in mother and stillbirth (erythroblastosis in infant)
  • tx- intrauterine transfusion

• mainly seen in SE Asia
• variable hemolytic anemia (microcytic)
• splenomegaly
• ineffective erythropoiesis and iron loading

• Hb AS (most common)
• Hb SS
• Hb SC
• Hb SB thal
• Hb SD (rare)