Possible Clinical Effects of Polymyxin B-Immobilized Fiber Columns via Platelet-Derived Lipid Mediators: A Prospective Observational Study.

INTRODUCTION

Endotoxin removal therapy using a polymyxin B-immobilized fiber column (PMX) has been reported to improve hemodynamics in patients with septic shock. However, the mechanisms underlying the blood pressure-increasing effects of PMX treatment remain unclear, and factors other than endotoxin adsorption may be involved. This study focused on vasoconstrictive lipid mediators in the blood and comprehensively analyzed these mediators in patients with septic shock.

METHODS

This prospective observational study included 10 patients with septic shock who underwent PMX treatment. Blood samples were collected at multiple time points up to 120 min after PMX initiation, and 23 lipid mediators were measured by mass spectrometry. Hemodynamic changes were evaluated using the vasopressor dependency index (VDI). Furthermore, platelet-rich plasma from healthy subjects was incubated with PMX fibers in vitro to assess platelet adhesion by electron microscopy and thromboxane production.

RESULTS

Among the 10 patients included, the plasma concentration of thromboxane B2 (TXB2), a stable derivative of thromboxane A2 (TXA2), was significantly higher at the PMX column outlet than at the inlet. This difference in TXB2 concentration showed a significant positive correlation with platelet count. Patients with higher platelet counts tended to exhibit a greater decrease in VDI, although the difference was not statistically significant. In vitro experiments demonstrated that platelets adhered to PMX fibers, accompanied by morphological changes, and that the fibers stimulated TXB2 production. Importantly, this production was suppressed by an antibody against the platelet surface antigen αIIbβ3.

CONCLUSION

TXA2, produced by platelets upon contact with PMX fibers during treatment, may contribute to the rapid increase in blood pressure observed after initiation of therapy.