Abstract Number: VPB0342
Meeting: ISTH 2022 Congress
Background: Opioid abuse is a major public health issue. To combat this problem, opioid tablets include excipients such as polyethylene oxide (PEO) to deter crushing and snorting. Yet, these deterrents do not protect against unintended intravenous injection. Intravenously injected PEO-containing opioids have led to complications such as hemolytic anemia, thrombocytopenia, and renal failure consistent with clinical features of thrombotic microangiopathy (TMA). In vivo and in vitro models have been used to demonstrate the hemolytic effect of high molecular weight (HMW) PEO above 4MDa, but the mechanism by which PEO causes TMA-associated events is not well understood.
Aims: The aim of this study is to assess the thrombogenicity of PEO by measuring clotting time and visualizing thrombus formation in an in vitro microfluidic model.
Methods: PEO solutions were prepared by dissolving PEO powder into phosphate buffered saline and then gently mixing with ACDA-anticoagulated porcine blood for 5min. The blood-PEO mixtures were then recalcified and heparinized. The effects of PEO concentration and molecular weight on blood coagulation were assessed using a Hemochron ACT+ system (Fig.1). To model thrombosis, blood-PEO mixtures were also perfused through a 100 x 200µm microfluidic model at 0.1mL/min (shear rate of 5,000s-1) for 20min and monitored for thrombotic events via microscopy.
Results: Increasing PEO concentration and molecular weight caused significantly shorter blood clotting times (Fig.1), especially for HMW PEO formulations above 4MDa. In the microfluidic model, no thrombosis was observed in the control microchannel, but thrombi were observed when HMW PEO was introduced (Fig.2). Thrombosis was more pronounced in the upstream region of the channel and appeared white in color, indicating the thrombi consisted mostly of platelets, not red blood cells.
Conclusion(s): Clotting occurred faster when HMW PEO was introduced into the blood, and white thrombi formed in an in vitro microfluidic model under high shear flow.
To cite this abstract in AMA style:Kim D, Herbertson L, Natu R, Malinauskas R, Baek J, Buehler P, Pinto J, Feng X, Qu H, Xu X. Effect of high molecular weight polyethylene oxide on thrombosis under high shear blood flow conditions [abstract]. https://abstracts.isth.org/abstract/effect-of-high-molecular-weight-polyethylene-oxide-on-thrombosis-under-high-shear-blood-flow-conditions/. Accessed October 2, 2023.
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