Case Hematology visit: – “Remote history of sickle cell trait” – FHx: Several children with sickle cell trait – Notes anemia entire life, denies blood loss – PE: normal (no LAD or HSM) F/u labs: – Normal iron studies, B12, folate – PB smear: Microcytic anemia possibly consistent with thalassemia trait. Recommend correlation with Hgb electrophoresis.
Revisiting clinical history – S/B thalassemia compound heterozygotes usually have symptoms (B+ = milder / B° = phenotypically identical to SSD) – Our patient has remained completely asymptomatic
Hemoglobin Electrophoresis Considerations with S/alpha thalassemia
Hemoglobin S, A, and A2 determined and compared among two groups. 82 normal controls 78 patients with sickle trait (A >>S) Sickle trait patients alpha globin status determined by PCR Alpha thalassemia cohort: 17 heterozygous, 13 homozygous Compared S and A2 levels among pure sickle trait vs S/alpha thalassemia
Percentage of Hb S decreases with more alpha gene deletions
MCV decreases with more alpha globin mutations single alpha gene mutations may be normocytic Hb A2 increases slightly with more alpha globin mutations
Mechanism α B A Hgb A1 B S Hgb S (30-40%) Normal Sickle Cell Trait S/alpha thalassemia Sickle Cell Anemia: -B globin SNP A T -6 amino acid position change -Glutamic acid (-) Valine (non-polar) αBABSBABS (+) (-) (+) ↑Hgb A1 ↓Hgb S ↑Hgb A2 Relative to Sickle Trait
Take Home S/alpha thalassemia causes slightly ↓Hgb S and ↑Hgb A2 relative to sickle cell trait The degree of change correlates with the number of alpha gene mutations Be careful of misinterpreting minor Hgb A2 elevations Utilize history when available When in doubt ask Charles
What is the “old” term for sickle cell disease (hint: think Greek)? DREPANOCYTOSIS Bonus
Acknowledgements Dr. Keren Charles Harmon Kristina Davis
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