LdhA^−/− mice developed an increase in platelet number. (A) Glucose metabolic flux analysis in mouse platelets by liquid chromatography/tandem mass spectrometry (n = 3). (B) LDH isozyme assay in mouse platelet, myocardium (heart), and skeletal muscle (muscle). (C) mRNA relative expression assay of LdhA and LdhB gene in mice tissues by quantitative real-time polymerase chain reaction (n = 3). (D) The protein expression of LDHA and LDHB in mouse platelet, myocardium (heart), and skeletal muscle (muscle). (E) Knockout-first strategy for creating conditional LdhA knockout mice. Recombination steps with Flp or Pf4-cre recombinase are illustrated. (F) mRNA relative expression assay of LdhA in LdhA^f/f and LdhA^−/− mice platelets by quantitative real-time polymerase chain reaction (n = 3). (G) The protein expression of LDHA in LdhA^f/f and LdhA^−/− mice platelets. (H) LDH isozyme assay in LdhA^f/f and LdhA^−/− mice platelets. Mice myocardium (heart) and skeletal muscle (muscle) were used as positive control. (I) Red blood cell (n = 5) and white blood cell (n = 5) counts in LdhA^f/f and LdhA^−/− mice peripheral blood. (J) Platelet counts in LdhA^f/f and LdhA^−/− mice peripheral blood (n = 5). (K) Mean platelet volume in LdhA^f/f and LdhA^−/− mice (n = 8). (L) Representative transmission electron microscope images of LdhA^f/f and LdhA^−/− mice platelets (n = 15, left). Scale bar, 50 nm. Total platelet section area was measured, and dense granule, α granule, and mitochondria numbers were counted. The data are expressed as granule numbers per unit area of counted section (right). Male mice 8 to 10 weeks old were used for these animal experiments. **P < .01, ***P < .001, ****P < .0001. 3PG, 3‐phosphoglycerate; Cit, citrate; F6P, fructose-6-phosphate; Fum, fumarate; G6P, glucose-6-phosphate; GA3P, glyceraldehyde-3-phosphate; Glu, glucose; Lac, lactate; Mal, malate; ns, not significant; PA, poly A; PEP, phosphoenolpyruvate; SA, splice acceptor; Suc, succinate.