A 38-year-old man with a history of sickle cell (SC) trait as a child, presented with priapism (panel A). He denied previous episodes of sickle crisis or priapism. A complete blood count showed mildly microcytic, normochromic anemia (hemoglobin [Hgb]: 11.4 g/dL; mean corpuscular volume: 81 fL; mean corpuscular hemoglobin: 28.8 pg), leukocytosis (white blood cells: 20.8 × 10⁹/L), and thrombocytosis (platelets: 3683 × 10⁹/L). A blood smear (panels B-C; ×100 magnification; Wright-Giemsa) showed increased target cells (orange arrows), rare Howell-Jolly bodies (green arrow), and scattered crystal-like condensations (black arrow), suggestive of hemoglobin SC disease that was confirmed on Hgb electrophoresis studies. Because the degree of thrombocytosis and presentation with priapism were unusual for Hgb SC disease, a bone marrow examination was performed and showed atypical megakaryocytic hyperplasia (panel D; ×20 magnification; hematoxylin and eosin) comprising large, hyperlobulated megakaryocytes (inset; ×100 magnification; Wright-Giemsa). Next-generation sequencing showed a type 2 CALR mutation (c.1154_1155insTTGTC p.K385fs*47; variant allelic frequency: 40%). The constellation of findings was diagnostic of essential thrombocythemia in this patient with Hgb SC disease.

This case highlights the importance of a comprehensive workup for additional etiologies of unusual presentations in such patients that are unlikely to be attributed to their underlying hemoglobinopathy.