[1224] Among Alpha Thalassemia Patients (pts), Genotypes Are Closely Associated with the Degree of Microcytosis/Mean Corpuscular Volume (MCV) Values

X Jiang, D Grisak, M Lareau, MTS Rad, A Mansoor. Calgary Laboratory Services (CLS)/University of Calgary, Calgary, AB, Canada

Background: thalassemia is characterized by quantitative defects in globin chain synthesis due to gene deletions. Minor deletions are associated with silent carrier (-/) or indolent clinical states (-/- OR --/) . Major deletions result in severe disease, like Hb H disease (--/-) or fatal Hydrops fetalis (--/--). It is an important D/D in hypochromic microcytic anemia with normal iron studies, specially in specific ethnic groups. Genotype determination is essential in thalassemia minor pts to avoid severe disease among offsprings. Identification of subset to be screened for gene deletion based on CBC data alone is difficult. In this study, we determined the association between MCV & various gene deletions in a cohort of hypo / microcytic anemia pts with normal iron studies.
Design: Analysis of 1,714 pts (> 95% non-Caucasian) with normal serum iron studies, referred for Hemoglobinopathy screening to our tertiary care facility was conducted. CBC / Iron studies were performed on automated analysers. Determination of Hb A2, HbF / etc was conducted by HPLC methodology (BIO RAD, Germany). Established single tube multiplex PCR screening (AJCP 2002), capable of detecting all genotypes was utilized in all. Pts were divided into group A: 12 yr (MCV ref. 82-100) and group B: 2-11 yrs (MCV ref. 75-91). Regression analysis was used to model for various genotypes. Chisquare test determined statistical correlation & p <0.05 was considered significant.
Results: In group A (n=1531, median age 43 yrs, range 12-93, M:F 0.7:1); MCV 73 was noted in 659(43%); 74-81 in 809 (53%) & 82 in 63 (4%) pts. In pts with MCV 73; 551 (84 %) had 2 gene deletions ((p <0.0001; PPV 81%; NPV 95%), majority (77%) being cis deletion (--/) (SEA: 83%). Pts with MCV 74-81, only 8% had 2 gene deletions, while most (443/809) (55%) had single gene deletion (3.7kb =55%; 4.2 kb= 7.7%). In group B (n=183; median age 6, M:F 1.3:1); MCV 68 was noted in 99(54%); MCV 69-74 in 59 (32%) and MCV 75 in 25 (14%). In pts with MCV < 68 (n=99), 70% had 2 gene deletions (p <0.0001; PPV 70%; NPV 90%); cis (73%) & tran (27%), (SEA: 65%). In pts with MCV 69-74, single gene deletion was most common (32/59 (54%) while 2 gene deletions was seen in only 5 pts (3%).
Conclusions: In thalassemia minor pts, MCV 73(adults) OR 68 (pediatric) are predictive of two gene deletions; while single gene deletion is most common when MCV is 74- 81 (adults) & 69- 74 (pediatric).
Category: Hematopathology

Wednesday, March 11, 2009 1:00 PM

Poster Session VI # 208, Wednesday Afternoon