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Over the course of COVID-19 pandemic, the use of ECMO has increased significantly. However, we find hemolysis happens gradually in ECMO, where RBCs experience periodic squeezes with low stress but high frequency. Such periodic squeezes lead to a progressive fatigue of RBCs with morphology changes before lysis. Deformation and recovery of RBCs under each squeeze are accompanied by ATP release and recovery. High squeeze frequency prevents the recovery of ATP, which results in the depletion of ATP and the consequent membrane-skeleton detachment for morphology change. This work establishes an empirical model for the fatigue of RBCs and reveals a different way of the hemolysis dominated by squeeze frequency, which brings a new insight into mechanism of hemolysis.