Hydrophilic Polymer Embolism: Implications for Manufacturing, Regulation, and Postmarket Surveillance of Coated Intravascular Medical Devices

Abstract

Hydrophilic polymers are ubiquitously applied as surface coatings on catheters and intravascular medical technologies. Recent clinical literature has heightened awareness on the complication of hydrophilic polymer embolism (HPE), the phenomenon wherein polymer coating layers separate from catheter and device surfaces, and may be affiliated with a range of unanticipated adverse reactions. Significant system barriers have limited and delayed reporting on this iatrogenic complication, the full effects of which remain under-recognized by healthcare providers and manufacturers of various branded devices. In 2015, the United States Food and Drug Administration acknowledged rising clinical concerns and stated that the agency would work with stakeholders to further evaluate gaps that exist in current national and international device standards for coated intravascular medical technologies. The present article reviews current knowledge on this complication as well as factors that played a role in delaying detection and dissemination of information and new knowledge once hazards and clinical risks were identified. Furthermore, organ-specific effects and adverse reaction patterns are summarized, along with implications for device manufacturing, safety testing, and regulation. Particulate analyses and general enhanced processes for device surveillance are needed to optimize vascular technologies and to ensure patient safety.

Intrathrombus polymer coating deposition: a pilot study of 91 patients undergoing endovascular therapy for acute large vessel stroke. Part I: Histologic frequency

“…Identification of specific polymer chemistry is not presented in the current report, and requires additional chemical particle analysis (eg, with Fourier transform infrared or Raman spectroscopy). As particulate deposits were not prospectively diagnosed in any of the 30 positive thrombus samples tested here, detection of polymer deposition in human tissues requires knowledge on this complication, an index of suspicion, targeted tissue sampling, and high-power microscopic analysis4; these factors each impact on test sensitivity. Despite this, good inter-reader agreement was observed in this retrospective analysis.…”

“…Potential sequelae of embolized polymer coatings to the brain have previously been reported, and include death, ischemic and/or hemorrhagic stroke, chronic neuroinflammation, headache, constitutional symptoms, seizures, and cognitive dysfunction 4–6 10–12 17–26. While steroids and immunosuppressive therapy have been shown to be beneficial in some patients who develop inflammatory responses, long-term outcomes, subclinical inflammatory responses, and implications of comorbid small vessel diseases have not been systematically investigated.…”

“…Although no correlation between polymer delamination and adverse patient outcome was identified in this investigation, 90-day mRS alone is not an appropriate measure for assessment of clinical significance. For future investigation, more standardized methods of clinical testing and formalized reporting of particulate size, loads, and intravascular effects has potential to impact on future guidance for biomaterial selection and standards 4 27…”

“…Coating particulate microembolism occurs commonly during endovascular procedures; however, quantitation of frequencies and risks of associated complications are underinvestigated. Furthermore, existing evidence shows that current preclinical simulated use testing is not fully predictive of device coating performances in real-world settings 4. To better understand the safety and integrity of device surface materials and procedural techniques, appropriate endpoints must be established and incorporated into preclinical testing and clinical trials designed to evaluate acceptable standards of device manufacturing and biomaterial use.…”

“…To better understand the safety and integrity of device surface materials and procedural techniques, appropriate endpoints must be established and incorporated into preclinical testing and clinical trials designed to evaluate acceptable standards of device manufacturing and biomaterial use. The importance of expanded preclinical in vitro safety testing has been acknowledged by the FDA,3 but further clinical investigation is needed and will likely drive preclinical testing requirements and industry standards 4. Large-scale, multi-institutional clinical device and tissue registries with long-term follow-up would facilitate characterization and comparative analyses of specific biomaterial and device effects in live patients, and will help identify source coatings.…”