1. CP Case Conference 11-21-2014 Martin Ishikawa

3. Case 73 yo AA female – geriatric clinic visit to establish care PMHx: osteoarthritis, migraines, DM, HTN PSHx: Knee, thyroid, lung, bunion, TAH Meds: Metformin, HCTZ, tramadol

4. Case cont. CBC: – Hgb: 10.1 – Hct: 30.8% – WBC: 7.4 – Plts: Clumped – MCV: 68.4 – RBC: 4.50 – RDW: 15.2 – WBC diff: WNL *MI: 15.2 Chem: – Na: 141 – K: 4.4 – Cl: 103 – HCO3: 26 – BUN: 17 – SCr: 1.06 – Gluc: 102 – Ca: 9.3 – HgA1c: 6.8%

5. 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.

7. My Mistake Microcytic anemia with significant increase in HgS and presence of HgA1. Noted increased HgA2 Assumed S/B+ compound heterozygote “I think you meant S/alpha thalassemia….”

9. Revisiting clinical history – S/B thalassemia compound heterozygotes usually have symptoms (B+ = milder / B° = phenotypically identical to SSD) – Our patient has remained completely asymptomatic

10. Hemoglobin Electrophoresis Considerations with S/alpha thalassemia

11. 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

12. Percentage of Hb S decreases with more alpha gene deletions

13. MCV decreases with more alpha globin mutations  single alpha gene mutations may be normocytic Hb A2 increases slightly with more alpha globin mutations

15. 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

18. 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

19. What is the “old” term for sickle cell disease (hint: think Greek)? DREPANOCYTOSIS Bonus

20. Acknowledgements Dr. Keren Charles Harmon Kristina Davis

21. Resources De Ceulaer K, Higgs DR, Hayes RJ, Serjeant BE, Serjeant GR. Alpha thalassemia reduces the hemolytic rate in homozygous sickle-cell disease. N Engl J Med. 1983 Jul 21;309(3):189-90. Head CE, Conroy M, Jarvis M, Phelan L, Bain BJ. Some observations on the measurement of haemoglobin A2 and S percentages by high performance liquid chromatography in the presence and absence of alpha thalassaemia. J Clin Pathol. 2004 Mar;57(3):276-80. Piel FB, Weatherall DJ. The alpha thalassemias. N Engl J Med. 2014 Nov 13;371(20):1908-16. Steinberg MH, Adams JG, Dreiling BJ. Alpha thalassemia in adults with sickle-cell trait. Br J Haematol. 1975 May;30(1):31-7. Steinberg MH, Embury SH. Alpha thalassemia in blacks: genetic and clinical aspects and interactions with the sickle hemoglobin gene. Blood. 1986 Nov;68(5):985-90.