Understanding clots and the first pass effect – Searching for answers to unsolved questions

Day 3 at SLICE 2019

Clot imaging on DSA and MRI

Drs Consoli and Bourcier spoke about clot composition. Dr Bourcier explored the susceptibility vessel sign (SVS) at the T2 gradient echo imaging (GRE). Interestingly, it is a sign present in about 70% of patients. And is related with better outcome of MT patients, better rate of recanalization.

A prospective randomized study called VECTOR is ongoing to test if SVS can affect the angiographic and clinical outcome.

Dr Charles Majoie described clot composition based on CT and CTA imaging. Hyperdense signs on the CT imaging can be also associated with different rate of recanalization. For example, the higher clot burden scores, the higher recanalization rate.

Permeability of the clot is also potentially associated with a higher recanalization rate. It can also be associated with higher effect of the IV-tPA, higher flow into the ischemic tissue. Santos et al (STROKE 2016) demonstrated a higher chance of recanalization after IV-tPA. A post hoc analysis of the MR CLEAN study focusing on clot composition showed a higher rate of TICI 2b-3 for clots with a sign of permeability and higher rate of better clinical outcome.  He also showed that calcified clots are associated with a quite high rate of failed MT.

Dr JP Desilles spoke about the COMPO-CLOT study. The action of the thrombolysis ID tested on the thrombus. Thrombus fixation showed also as a shell around the clot presenting poor concentration in red blood cells and extracellular matrix. This shell can impair fibrinolysis because it is more resistant to lysis. In conclusion, research illustrated thrombus presenting particular types of external shells are more resistant to IV t-PA due to the non-fibrin composition.

Dr Cyril Dargazanli from Montpellier spoke about the proteomics of intracranial thrombi. The hypothesis is that proteomics can be associated with the nature of the thrombi with a potential clinical impact. An ongoing study in Montpellier is analyzing thrombi composition after retrieval by MT. Sixty samples were obtained in two years.  Based on some selected proteins found by this analysis, precisely 3 combinations of proteins, we could be able to detect the etiology of the stroke itself.

Dr Heleen Van Beusekom discussed clot adhesion and stent retrievers. There are different types of interactions: mechanical (in about 44% of cases) and active interactions (in about 56%). Active interactions were associated with different types of clot composition. Dense networks appeared to be associated with active adhesion, loose networks with mechanical adhesion.  In conclusion, improving understanding of the clot adhesion can impact the choice of the stent or changes in tPA. The faculty discussed the possibilities of developing stent coatings presenting better interaction with the clot.

Dr Simon F. de Meyer continued with the discussion on the clot histology and structure. It was of interest that the different compositions of the clot, such as the von Willebrand factor, can be a new thrombolytic target in ischemic stroke (Denorme F et al, Blood, 2016). Also, neutrophil extracellular cells can be associated with inflammation and a different etiology of the thrombi and outcomes. A DNA shell has also been detected, and potentially DNase treatment can be developed as a molecular target. In conclusion, the many different compositions of a clot, such as platelet, fibrin, VWF, DNA, can affect the rate of successful treatment after MT.

Sponsored symposium

A specific guidewire, sponsored by SENSOME, can detect the composition of the clot. Mainly, this guidewire will be capable of distinguishing reach-fibrin and RBC-reach clot and will be probably available in the market in the next few months.

Dr O. Zaidat spoke about the impact on the outcome of the first pass effect, as has been shown in the ARISE II trial.  A first pass effect is likely independent from the time from puncture-to-recanalization. Dr Zaidat argued that the new goal is TICI 2b-3 after the first pass effect.  The first pass effect is also associated with significant cost saving.

What is the physiological explanation of the first pass effect? It is likely related to the interaction between thrombus and endothelium, and endothelium damage.

In conclusion, a maximalist approach, longer stents, balloon guiding catheter should be used to achieve the first pass effect.

Conclusions

Prof. Wim Van Zvam offered a comprehensive review of the literature underlining the evidences of stroke treatment.

He demonstrated that current literature underlined MT as cost-effective. MT indications have now been enlarged by years.

The last part of this year’s SLICE was dedicated to the creation of suggestions by experts regarding unsolved questions. A panel discussion called “OUR CHOICES WHILE AWAITING EVIDENCE” produced an interesting synthesis of the congress as well as a series of practical suggestions concerning several of the important questions.

 

Federico Cagnazzo
Federico Cagnazzo

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