Accelerated production of hyperreactive young platelets in Jak2^VF CH. (A) Effect of JAK2^VF on platelet indices in the UK Biobank cohort adjusted to platelet counts (in addition to age, sex, square of age, smoking status, first 5 genetic principal components, graph shows effect size as SD with 95% CI). (B) Fraction of young (reticulated) platelets. (C) Platelet production rate per hour. (D) Relative platelet life span. (E) Platelet size. (F-L) Intravital bone marrow imaging of thrombopoiesis in Jak2^VF CH and control mice. (F) Experimental design and representative Alexa 488 anti-mouse glycoprotein IX– and phycoerythrin anti-mouse Ly-6G–labeled images (arrow indicates proplatelets [PPs], and arrowhead indicates MKs, green color; red color shows neutrophils; see also supplemental Videos). Analysis of PP release relative to MK numbers (G), MK size (H), relative MK number (I). (J-L) Frequency distribution or abundancy of different PP-releasing MK-subgroups (3pp-MK most PP producing, 1pp-MK least PP producing) (J) and their contribution to MK size (K) and PP-release time (L). (M-N) Relative activation of young as compared with old platelets shown for thrombin-induced P-Selectin surface expression (M), GPIIbIIIa activation (JON/A, N) and binding of fibrinogen (O) in Jak2^VF CH and control mice. (P) Contribution of young platelets to platelet-leukocyte heteroaggregates in the whole blood of Jak2^VF CH mice. In panels H, K, and L, data points present single MKs in different bone marrow areas from 4 different animals. ∗P < .05; ∗∗P < .01; ∗∗∗P < .001; Student t test or Mann-Whitney U test, as appropriate. PMA, platelet-monocyte aggregation; PNA, platelet-neutrophil aggregation.