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Gradual deterioration of red blood cells ( RBCs ) due to mechanical stress (chronic hemolysis) is unavoidable during treatments that involve extracorporeal blood circulation, such as hemodialysis ( HD ). This effect is generally undetectable and does not generate any acute symptoms, but it leads to an increase in plasma free hemoglobin (  fHb  ). There are no absolute safety levels for   fHb   increase, indicating the need for an empirical evaluation using comparative testing. The increase in   fHb   levels was investigated in vitro by applying double‐needle double‐pump  HD  ( HD‐DNDP ), a new modality in which arterial and venous pumps both run continuously.   fHb   was measured during typical and worst‐case simulated dialysis treatments (double‐needle single‐pump  HD  [ HD‐DNSP ], hemodiafiltration [ HDF‐DN ], single‐needle double‐pump  HD  [ HD‐SNDP ], and  HD‐DNDP ) performed in vitro using bovine blood for 4 h. Hemolysis‐related indices ( fHb% ; index of hemolysis,   IH  ; and normalized   IH  ) were calculated and used for comparison. The increase in   fHb   during either  HDF‐DN  or  HD‐SNDP  with  A rtis and  AK 200 dialysis machines was similar, while the   fHb   at the maximum real blood flow rate (  Qb real   ) at the completion of the  HD‐DNDP  treatment on  A rtis was higher than that for  HD‐DNSP  using a  P hoenix dialysis machine (  fHb   %  = 1.24 ± 0.13 and 0.92 ± 0.12 for the  A rtis machine with  HD‐DNDP  at   Qb real    = 450 mL/min and  P hoenix with  HD‐DNSP  at   Qb real    = 500 mL/min, respectively). However, the   fHb   levels increased linearly, and no steep changes were observed. The increases observed during  HD‐DNDP  were the same order of magnitude as those for widely used bloodlines and treatment modes for delivering dialysis treatments. The observed results matched literature findings, and thus the measured   fHb   trends are not predicted to have clinical side effects.  HD‐DNDP  treatment with  A rtis does not merit any additional concern regarding mechanical stress to  RBCs  compared with that observed for routinely used dialysis treatments, bloodlines and machines. Although the in vitro measurement of the   fHb   increase in bovine blood does not allow a prediction of the absolute level of blood mechanical damage or the possible effects in humans, such measurements are valuable for assessing hemolytic harm by performing tests comparing the proposed treatment with existing devices.

In Vitro Comparative Assessment of Mechanical Blood Damage Induced by Different Hemodialysis Treatments