Version July 2025
| HSt | SAO | |
| First line (done in all patients) | ||
| Complete blood count (CBC) | Variable degree of anemia and reticulocytosis Increased MCV, MCH, and/or MCHC | Variable degrees of anemia and reticulocytosis, typically resolves by early childhood Decreased MCV may be seen |
| Blood smear | Dehydrated HSt: <20% stomatocytes (absence of stomatocytes in some cases) Overhydrated HSt: >20% stomatocytes | Ovalocytes, stomatocytic ovalocytes/elliptocytes, or theta cells (ovalocytes with two slits) |
| Family history for inheritance pattern | Autosomal dominant | Autosomal dominant |
| Second line (at least one of these tests is done in patients with suggestive findings on first-line testing) | ||
| Osmotic fragility (OF) | Dehydrated HSt: Decreased OF Overhydrated HSt: Increased OF | (Not well studied) |
| EMA binding | Normal to increased | Decreased |
| Ektacytometry | Dehydrated HSt: Left shift of the osmolarity curve for pathogenic variants in PIEZO1 Overhydrated HSt: Right shift of the osmolarity curve | Flattening of the osmolarity curve with undeformable feature and DImax close to zero |
| Third line | ||
| Genetic testing (Sanger sequencing, NGS panel, or whole exome sequencing)* | Pathogenic variant in one of the following:
| Specific 27 base pair deletion (Δ400-408) |
CDA: congenital dyserythropoietic anemia; DBA: Diamond-Blackfan anemia; EMA: eosin-5-maleimide; HSt: hereditary stomatocytosis; MCH: mean corpuscular hemoglobin; MCHC: mean corpuscular hemoglobin concentration; MCV: mean corpuscular volume; NGS: next-generation sequencing; OF: osmotic fragility; RBC: red blood cell; SAO: Southeast Asian ovalocytosis.
* NGS panels for hereditary RBC disorders may evaluate genes that encode for membrane proteins, enzymes, iron regulatory proteins, and specific conditions such as DBA, CDAs, or sideroblastic anemias.