CP Case Conference

11-21-2014Martin Ishikawa

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

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%

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.

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….”

• 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 BA Hgb A1

α BA Hgb A1 BS Hgb S (30-40%)

Normal

Sickle Cell Trait

S/alpha thalassemia

Sickle Cell Anemia:-B globin SNP AT -6 amino acid position change-Glutamic acid (-) Valine (non-polar)

α BA

BS

(+) (-)

(+)

↑Hgb A1↓Hgb S↑Hgb A2

Relative to Sickle Trait

𝛿

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

ResourcesDe 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.