Mild erythrocytosis as a presenting manifestation of PIEZO1 associated erythrocyte volume disorders

Tristan Knight, Ahmar Urooj Zaidi, Shengnan Wu, Manisha Gadgeel, Steven Buck, Yaddanapudi Ravindranath

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


Piezo1, encoded by the gene PIEZO1, is an erythrocytic cellular membrane mechanoactivated cation channel. Mutations have been implicated in erythrocyte volume disorders (EVDs)—especially hereditary xerocytosis (HX)/dehydrated stomatocytosis (DHS). We identified three patients, all with novel PIEZO1 mutations, but only one displaying the HX/DHS phenotype. Retrospective review of three cases. Osmotic gradient red cell deformability (Osmoscan) was assessed via the Technicon Ektacytometer. Red cell band 3 content was estimated using Eosin-5′-Maleimide staining. Patient 1 was evaluated for polycythemia. Osmoscans suggested mild spherocytosis; a novel PIEZO1 mutation (p.Thr1589Ile, exon 35) was identified, causing mild erythrocytosis without hemolytic anemia. Patient 2 was evaluated for macrocytosis/reticulocytosis, normal-to-high hemoglobin, and indirect hyperbilirubinemia. Osmoscans suggested increased cellular hydration; a second novel PIEZO1 mutation (p.Arg1728Cys, exon 37) was identified, resulting in overhydrated stomatocytosis with well-compensated hemolysis. Patient 3 was evaluated for indirect hyperbilirubinemia only. Osmoscans suggested dehydrated stomatocytosis (DHS, xerocytosis); a third novel PIEZO1 mutation (p.Arg2279Cys, exon 47) was identified. All three patients’ blood smears demonstrated stomatocytes and spherocytes. EVDs may be underdiagnosed due to the lack of “expected” anemia in a hemolytic disorder; two of three patients had high hemoglobin and red cell counts and one had high normal values for both parameters and the presence of stomatocytes/dehydrated cells lead to identification of causative PIEZO1 mutations. PIEZO1-associated EVDs may be more common than previously suspected and should be included in the diagnostic algorithms for mild erythrocytosis/unexplained jaundice.

Original languageEnglish
Pages (from-to)317-326
Number of pages10
JournalPediatric Hematology and Oncology
Issue number5
StatePublished - Jul 4 2019
Externally publishedYes


  • Erythrocyte membrane
  • PIEZO1
  • erythrocyte volume disorders
  • erythrocytosis
  • hemolytic anemia
  • osmotic gradient ektacytometry
  • stomatocytosis
  • xerocytosis


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