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Transl. Med."],"published-print":{"date-parts":[[2026,10,7]]},"abstract":"<jats:p>\n                    Thrombotic events are the leading cause of death in myeloproliferative neoplasms (MPNs) driven by the JAK2 Val\n                    <jats:sup>617<\/jats:sup>\n                    \u2192Phe (JAK2V617F) mutation. We investigated how JAK2V617F alters hemostasis and thrombosis in humans and in lineage-specific knockin mice to test whether red blood cell (RBC) mechanics contribute directly to clot pathology.\n                    <jats:italic toggle=\"yes\">\n                      Jak2\n                      <jats:sup>F\/+<\/jats:sup>\n                      Vav-Cre\n                    <\/jats:italic>\n                    knockin mice form structurally aberrant clots characterized by extended clot formation times and unstable hemostatic plug formation. Whole-blood clot contraction in vitro was impaired in humans and mice carrying the JAK2V617F mutation, even when\n                    <jats:italic toggle=\"yes\">\n                      Jak2\n                      <jats:sup>V617F<\/jats:sup>\n                    <\/jats:italic>\n                    erythrocytes were resuspended in normal plasma with normal platelets. Thus, in addition to increasing the hematocrit, the JAK2V617F mutation imparted intrinsic changes in erythrocytes critical for mediating abnormal clot formation. Biophysical analysis showed that\n                    <jats:italic toggle=\"yes\">\n                      Jak2\n                      <jats:sup>V617F<\/jats:sup>\n                    <\/jats:italic>\n                    erythrocytes had stiffened membranes, making them less compressible during clot contraction. Proteomic and lipidomic analysis of\n                    <jats:italic toggle=\"yes\">\n                      Jak2\n                      <jats:sup>V617F<\/jats:sup>\n                    <\/jats:italic>\n                    erythrocytes revealed the loss of key membrane and cytoskeleton proteins, a sparse spectrin cytoskeletal network, increased membrane lipid content, and deep plasma membrane invaginations that were consistent with biaxial cytoskeletal stretching and altered lipid packing. These JAK2V617F-driven changes in erythropoiesis generated intrinsically rigid erythrocytes that impaired clot contraction and produced larger and more occlusive, yet mechanically unstable thrombi. This mechanism may explain the contradictory coexistence of thrombosis and hemorrhage in MPNs and why both complications improve when blood counts are lowered, suggesting that targeting erythrocyte mechanics may provide previously unidentified therapeutic opportunities.\n                  <\/jats:p>","DOI":"10.1126\/scitranslmed.adt0044","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T17:58:16Z","timestamp":1791395896000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Aberrant erythrocyte rigidity in JAK2\n                    <sup>V617F<\/sup>\n                    myeloproliferative neoplasms underlies concurrent thrombosis and hemorrhage"],"prefix":"10.1126","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-4569-6972","authenticated-orcid":true,"given":"Aae","family":"Suzuki","sequence":"first","affiliation":[{"name":"Department of Medicine, Perelman School of 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