A protamine bio-reactor for extracorporeal heparin removal: In vitro modeling, function assessment, and future direction

Tanya Wang, Youngro Byun, Jae Seung Kim, Junfeng Liang, Victor C. Yang

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Heparin, employed during extracorporeal blood circulation (ECBC) procedures (e.g. cardiopulmonary bypass), is often associated with a high incidence of bleeding complications. Protamine, employed in heparin neutralization, at times causes severe adverse reactions. To overcome this clinical dilemma, we previously proposed an approach that placed a blood filter device with immobilized protamine (termed a "protamine bio-reactor") at the distal end of the ECBC circulation. The protamine bioreactor would externally remove heparin using immobilized protamine, thereby simultaneously eliminating both heparin and protamine-induced complications. Both in vitro and in vivo experiments have demonstrated the feasibility and utility of this approach. In order to design an efficient protamine bio-reactor, the relationships between the reactor capacity and initial heparin concentration (CRO), protamine loading, saturation concentration (CS), reactor size (N, number of fibers), and flow rate needed to be established. The object of this investigation was to develop a numerical model that could be used to optimize the protamine bio-reactor for future studies. Protamine was immobilized to cellulose hollow fibers using a cyanogen bromide activation method. The maximum amount of immobilized protamine on the fibers was estimated to be 1620mg protamine/g fiber, whereas the maximum reactor capacity (CS) was estimated to be 8.9 mg heparin/g fiber. By utilizing the plug flow reactor model, the heparin binding constant (ka was determined from experimental data to be 2.8 × 103 M-1 min-1. Based on targeted values for CS and ka, the numerical model provided a performance assessment for an optimized protamine bio-reactor under real clinical situations of hemodialysis (HD) and cardiopulmonary bypass (CPB). This assessment led to a conclusion that a two bio-reactor, bio-feedback system would in the future achieve a most effective heparin removal for real clinical situations.

Original languageEnglish
Pages (from-to)133-149
Number of pages17
JournalInternational Journal of Bio-Chromatography
Volume6
Issue number2
StatePublished - 2001

Keywords

  • Bio-feedback system
  • Heparin removal
  • Mathematical modeling
  • Protamine bio-reactor

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