Iatrogenic Extremity Ischemia with the Potential for Amputation

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

“…Although recommendations outlined in AAMI TIR 42 41 suggest that manufacturers introducing new devices should obtain comparative data on particulate matter from predicate devices, the safety and efficacy of predicate devices are unproven. Furthermore, clinical evidence shows that established preclinical simulated use testing is not fully predictive of device coating performances in real-world settings 2–46 . Current ISO10993 standards do not specify in vivo testing procedures for degradable polymeric devices, including screening of device surface changes upon animal or human blood contact, analyses of vessel-device interface reactions, determination of degree, quality and/or rates of intravascular coating biodegradation and particulate release, or analyses of biological implications of polymer deposits within distal vasculature and end organs 5,6,42 .…”

“…2, Table 2). Adverse reactions have been documented in patients aged 2 months to 89 years 43,44 and have involved the heart, 5,[15][16][17]19,20,27,28 lungs, 4,5,10,33 brain, 2,3,5,8,9,18,26,36,40,43 kidneys, 17,24 skin/subcutaneous tissues and extremities, [12][13][14][21][22][23]25,29,34,35,44 arteriovenous and transplant grafts, 9,17 colon, 31 spinal cord, 5 liver, 7 spleen, pancreas, adrenal glands, and muscle (Table 1) and on occasion have been associated with multisystem involvement, including multiorgan injury and/or systemic inflammatory response syndrome. 5,7 Recognized organ-specific reactions and clinical sequelae are summarized in Table 2.…”

“…With expanded knowledge and gradual increase in recognition of predicted tissue appearances and effects, however, there has been a marked increase in HPE reporting over recent years (Fig. 1, Table 1) [2-44].…”

“…Following localized access site deposition or embolism to distal organs, polymeric deposits measuring up to 1.9 mm in cross section and 2.3 cm in longitudinal section, have been shown to induce vasoocclusion, in most cases with associated intra- and/or peri-vascular inflammation, thrombus formation, and/or fibrosis (Fig 2, Table 2). Adverse reactions have been documented in patients aged 2 months to 89 years [43,44] and have involved the heart [5,19-21,24,27,29,33], lungs [4,5,10,28], brain [2,3,5,8,9,18,22,30,40,43], kidneys [21,23], skin/subcutaneous tissues and extremities [12-17,25,26,31,32,44], arteriovenous and transplant grafts [9,21], colon [35], spinal cord [5], liver [7], spleen, pancreas, adrenal glands and muscle (Table 1), and on occasion have been associated with multisystem involvement, including multiple organ failure and/or systemic inflammatory response syndrome [5,7]. Recognized organ-specific reactions and clinical sequelae are summarized in Table 2.…”