Question is “not if, but when” to stent in challenging, NET-rich clots

Tommy Andersson presenting at BRAIN 2023

The recent Barts Research and Advanced Interventional Neuroradiology (BRAIN) conference (4–6 December 2023, London, UK) saw Tommy Andersson (Karolinska University Hospital, Stockholm, Sweden) put forward the case for post-thrombectomy rescue stenting in ischaemic strokes caused by challenging, neutrophil extracellular trap (NET)-rich clots.

“NETs interact with platelets, and are specifically abundant in red blood cell-poor and platelet-rich clots,” Andersson informed the BRAIN audience, also stating it is “definitely” possible that failed revascularisation post-thrombectomy could be caused by the clot being rich in NETS. “And, stenting is probably the best bailout option for difficult, NET-rich clots—but maybe not for ICAD [intracranial atherosclerotic disease], at least with the materials we have available today, because then we see risks of snow-ploughing or cheese-grating. It can, however, sometimes be very difficult to differentiate a difficult clot from ICAD.”

Initially covering potential reasons for a mechanical thrombectomy failing to achieve successful revascularisation, Andersson relayed that ICAD is “fairly common”, but mainly observed in Asian populations, while intracranial dissections are “very uncommon”. However, challenging clots—which tend to be rich in platelets, dense fibrin, von Willebrand factor, and/or NETs—are more prevalent and represent a “big problem”, particularly in Europe, due to their resistance to both thrombolytic drug therapies and thrombectomy procedures.

“We have long said that dense fibrin is the bad guy,” Andersson noted. “But, maybe it’s not so much the dense fibrin—maybe it’s the platelets. And, maybe it’s the platelets in combination with NETs. [Another] problem is that the clots that we can analyse are the ones that we can get out, but the clots that we cannot take out are unable to be analysed.”

Here, Andersson referenced a national registry in Sweden that has gathered data on “every single” stroke thrombectomy in the country since 2013, including collecting and analysing clot information from some 14,000 patients. A closer look at histopathological data from “unusual” clots considered to be outliers versus more common clot compositions in the registry indicated that these were all “very difficult” to remove. Andersson said this exercise also revealed higher-than-average levels of extracellular DNA—many times, in conjunction with microcalcification—in these outlier clots.

“So, no wonder we had problems removing them,” he quipped, going on to cite multiple studies seen in an earlier presentation from Simon de Meyer (Catholic University of Leuven, Kortrijk, Belgium) suggesting that NET-rich clots often take “a lot of time and effort” to remove.

Offering possible solutions to the challenge posed by NET-rich clots, Andersson went on: “Once you have tried—and failed—using your favourite first-line strategy, you could attempt more advanced materials or techniques, like two stent retrievers, or the Nimbus [Cerenovus/J&J].”

The latter device—described by Cerenovus as a geometric clot extractor that is “designed to remove tough clots”—offers one “pretty good” alternative to more traditional tools that “may actually work” in more difficult, NET-rich clots, according to Andersson. However, this technology and double stent-retriever methods would “basically be useless” in ICAD cases, he added.

Andersson continued: “But, if we still fail, what should we do? Should we stent—and, if so, when, and after how many attempts? For me, the question is not ‘if’, but ‘when’, we should stent, because that’s the bailout for a difficult clot.”

The speaker then averred that, while existing data indicate an increased number of thrombectomy attempts being linked to worsening outcomes, the “worst outcome” is to leave the vessel occluded.

“The worst thing you can do is to leave the vessel occluded,” he added. “That is never, ever good.”

Moving on to the pros and cons of balloon angioplasty as a post-thrombectomy rescue strategy, Andersson noted that this adjunctive technique does mean dual antiplatelet therapy (DAPT) can be avoided. However, balloon angioplasty in ICAD cases creates the potential problem of ‘snow-ploughing’, he posited, also citing challenges around balloon grading, which can lead to the operator overinflating the device; target-vessel re-occlusion due to recoil at the end of the procedure; and the “very real” risk of dissections and ruptures, potentially causing “catastrophic events”.

After warning neurointerventionists to “be careful with balloons”, Andersson disclosed that his own paradigm for tackling difficult clots is to try a given approach once or, at most, twice—for example, with two stent retrievers or the Nimbus device—before reverting to stenting.

Andersson rounded out his talk by stating that there are “quite a few” published papers supporting rescue stenting, specifically highlighting one of several meta-analyses on this topic that was published in 2020 in Interventional Neuroradiology by the Salpêtrière group from Paris, France. The paper concluded that permanent intracranial stenting after failed thrombectomy “appears” to improve clinical outcomes, before adding that further trials are needed to confirm this.

According to Andersson, a randomised trial—the “holy grail” for many—is currently being conducted by the same group, led by Kévin Premat (Charles Foix Hospital, Paris, France), and, as such, “we will see” what the most appropriate thrombectomy rescue strategy is in due course.


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