Did you know that erythrocyte sickling was recognized in deer blood 70 years before sickled erythrocytes were documented in humans in 1910? Some species of deer and sheep have sickled erythrocytes in blood films, but they do not develop anemia or other clinical signs like those associated with sickle cell anemia in humans? The reason is that sickled erythrocytes (also called drepanocytes) develop in vitro, but not naturally in vivo in deer. In humans, erythrocytes sickle when oxygen tension and pH are low (deoxyhemoglobin predominates), as occurs in tissues other than lungs. In contrast, deer erythrocytes sickle when oxygen tension and pH are high (oxyhemoglobin predominates), as occur when venous blood samples are exposed to air (hemoglobin is oxygenated and carbon dioxide is released). Sickled erythrocytes have been produced in vivo experimentally in anesthetized deer by giving intravenous bicarbonate while being ventilated with 100% oxygen. A single amino acid substitution in the beta chain of adult hemoglobin results in hemoglobin polymerization into fibrils in humans with sickle cell anemia. Similarly, a single ancestral amino acid change in beta chains of hemoglobin in some deer species accounts for the in vitro sickling in deer erythrocytes. Learn more here.