Incidental finding of 3 Southeast Asian ovalocytosis cases by attentive examination of blood smears

Abstract

A 52-year-old Malaysian man, a 24-year-old sub-Saharan woman, and a 28-year-old Madagascan woman (who was heterozygous for hemoglobin S) were admitted to North Hospital in Marseilles, France. Blood tests using an Advia2120i hematology analyzer (Siemens) showed no or mild anemia (109-150 g/L), normal or high mean corpuscular hemoglobin concentration (339-364 g/L), and borderline or slightly high red cell distribution width (15%-19.2%).The red blood cell (RBC) volume and hemoglobin concentration cytogram clearly showed a typical distribution of comma-shaped RBCs, with an increased number of hyperchromic RBCs (panel A). Examination of the blood smear revealed anisocytosis and poikilocytosis, without spherocytes but with ovalocytes and macro-ovalocytes, some of them with more than 1 ridge (panel B; original magnification 3100, May-Grünwald Giemsa stain). The eosin-59-maleimide binding test performed for each patient showed a reduced mean channel fluorescence between 26.2% and 30.9%, confirming an anomaly of the band-3 protein. A heterozygous 9-amino-acid deletion (residues 400 to 408) in band 3 (SLC4A1), which is the most common genetic abnormality in Southeast Asian ovalocytosis (SAO), was found in all 3 patients. Most cases of SAO are asymptomatic, so careful examination of a cytogram from the Advia2120i analyzer and close observation of the blood smear can help diagnose SAO.For additional images, visit the ASH IMAGE BANK, a reference and teaching tool that is continually updated with new atlas and case study images. For more information visit http://imagebank.hematology.org.

Hemolysis in the spleen drives erythrocyte turnover

“…12,13 In contrast to sickle cell disease and spherocytosis, SAO is clearly not associated with large-scale erythrocyte destruction. 14 This is one of the reasons why it has been proposed that, next to loss of deformability, other factors may contribute to retention of erythrocytes within the spleen, leading to their turnover. One example is the activation of adhesion molecules such as Lu/ BCAM and CD44 specifically on aged erythrocytes.…”

The Gardos effect drives erythrocyte senescence and leads to Lu/BCAM and CD44 adhesion molecule activation

“…51 Surprisingly, these individuals are clinically asymptomatic with no signs of anemia. 52 These individuals, along with the majority of elliptocytosis patients, are examples in which marked loss of erythrocyte deformability is not associated with their massive sequestration, arguing in favor of the hypothesis that next to mechanical retention, other factors such as adhesion molecule activation as a result of Ca 21 influx and Gardos channel activation, may contribute to erythrocyte turnover. Thus, it would be of interest to study adhesion molecule activation on these erythrocytes.…”