112 K . Kashiwa et al .: J Extra Corpor Technol 2024 , 56 , 108 – 113
circulation may be suppressed during surgery , although there was no evident difference in preoperative immunosuppression status between groups in this study .
Currently , the infusion rate of UFH is adjusted using ACT as a main indicator . Taking the result of the present study into consideration , the WBC count , rather than the platelet count , could be an additional useful reference parameter to fine-tune the dosage of UFH during VA-ECMO in lung transplantation . However , it should be noted that several confounding factors such as intensity of surgical invasion and amount of blood transfusion might have significant impacts on the association of WBC count with UFH infusion rate . Adjusting these factors by multivariable analysis was difficult because of the small sample size of this study . However , these factors might be assumed not to influence WBC counts largely because we observed significant differences in WBC counts between the groups at the early phase of 1 – 2 h after starting ECMO . Further investigation is necessary to clarify the cause of the increase in WBC count and the mechanism of effect on ACT .
Limitations
The present study has several limitations . First , this is a single-center , retrospective analysis . Multicenter prospective analysis is necessary to confirm the finding obtained in the present study . Second , all the patients were treated with the same initial infusion rate of UFH and the grouping of patients ( i . e ., increased and non-increased ) is relative to the initial dosage . However , even if the initial infusion rate of UFH was set at a higher dose , for example , we speculate a similar relationship was observed among ACT , adjustment of dosages of UFH , and WBC count . Third , we adjusted the UFH infusion rate based only on ACT this time . It remains unclear whether similar results will be obtained when adjusting the infusion rate using other parameters for monitoring coagulation . However , other laboratory tests such as APTT or Xa activity will not be useful because rapid adjustment of anticoagulant therapy is required during lung transplantation surgery . Other blood viscoelasticity test equipment that can be used as point-of-care tests will cost much for multiple measurements during surgery . Fourth , although antithrombin ( AT ) was also another potential confounder , AT was not measured in all the patients in this study . Finally , the sample size in this study was small and the result is preliminary . Therefore , this study is better to be positioned as a pilot study . To confirm the results , further investigations are necessary with larger sample sizes determined by sample size calculation based on this study .
Conclusion
This retrospective observational study demonstrated that increased WBC count during lung transplantation surgery was associated with the requirement of an increase in UFH infusion rate in V-A ECMO management . The obtained findings suggested the possible impact of inflammation on anticoagulation management in ECMO during lung transplantation surgery .
Funding This research did not receive any specific funding .
Conflicts of interest None declared .
Data availability statement
Data are available from the corresponding author on reasonable request and with permission of the institutional review board of the University of Tokyo .
Author contribution statement
K . Kashiwa , M . Sato , K . Doi designed the studies . H . Kurosawa , K . Fujishiro , H . Kubo performed the research and analyzed the data . R . Inokuchi , M . Bougaki , G . Kawamura , C . Konoeda , J . Nakajima provided expertise in clinical data analysis . K . Kashiwa , M . Sato , K . Doi wrote the manuscript , and all authors contributed to the final version .
Ethics approval
Data collection was conducted as a retrospective cohort study to clarify whether clinical inflammatory parameters were associated with the required dosage of UFH to maintain the range of ACT in V-A ECMO during lung transplantation . The study protocol conformed to the Declaration of Helsinki and was approved by the Ethics Committee of the University of Tokyo Graduate School of Medicine / School of Medicine , Bunkyo-city , Tokyo , Japan . Medical research is subject to ethical standards that promote and ensure respect for all human subjects and protect their health and rights .
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