Transmission electron microscopy of “yarn/knitting needle” RBCs when deoxygenated in vitro. “Yarn/knitting” RBCs are irreversibly sickled cells, that is their shape does not change according to the presence or absence of intracellular polymer. These cells were likely formed by the presence of a single domain of polymer transecting the cell and growing to the extent that the membrane loses its elasticity and the deformation becomes permanent. By deoxygenating peripheral blood from a patient with a high expression of S-Oman we observed the type of domain formation that occurs in these cells. Notice that a single large domain is forming in the center (B and C), but much smaller domains are also formed, in the distal extension of the membrane as well as immediately under the membrane, as magnified in (D). (A) This RBC has a “banana” shape, capable of accommodating two long polymer domains separated by an angle approaching 180°: indeed, two major domains are being formed upon in vitro deoxygenation in these cells, following the requirement of the already established irreversibly deformed shape.