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Intravenous abciximab as a rescue therapy in stroke patients

By Delvoye et al., 2021


Background

Recanalization involves the adhesion of the thrombus to the vein wall. An inflammatory response leads to thrombus contraction and spontaneous lysis of the thrombus. Durable recanalization is typically linked to a good clinical outcome after mechanical thrombectomy (MT) in acute ischemic stroke patients (AIS).


Lack of recanalization occurs due to an impossibility of retrieving the occlusive clot or an immediate reocclusion after the initial recanalization, which happens in 19% of the cases.

Evidence shows that patients with an elevated platelet count at admission were more likely to have early reocclusion after successful MT. So, platelets may play an essential role in immediate reocclusion in AIS patients.


Researchers at the Rothschild Foundation Hospital in Paris, France, conducted a retrospective analysis of the safety and efficacy of IV abciximab administration (a monoclonal antibody that blocks platelet aggregation) used as a rescue therapy for immediate reocclusion in MT-treated AIS patients and compared its antithrombotic activity to that of tissue plasminogen activator (tPA) in vitro.


Methods

Antithrombotic Activity of Abciximab and Alteplase in Flowing Human Blood

The group assessed the individual and combined effects of abciximab and alteplase on clot formation. For that, they collected human whole blood from healthy volunteers and perfused it for 4 min at an arterial wall shear stress of 62.5 dynes/cm2 in channels of Vena8 Fluoro+ Biochips (Cellix) coated with collagen (0.5 μg) and tissue factor (600 pM). Before perfusion, they incubated the blood for 5 min with 3,3′-dihexyloxacarbocyanine iodide (10 μM) and AF-647- conjugated fibrinogen (100 μg/mL) in the presence of abciximab at 3.5 μg/ml and alteplase at 15 μg/mL.

Immediately after blood perfusion, they washed the channels with buffer. After that, they acquired the images using a microscope equipped with a camera coupled with image capture software. Finally, they quantified platelet and fibrin accumulation according to the mean fluorescence intensity along the entire channels.


Main findings of these experiments

  • The perfusion of human whole blood over the microfluidic channels coated with collagen and tissue factor led to the formation of platelet- and fibrinogen-rich thrombi (Fig 2).

  • Adding alteplase before perfusion prevented fibrinogen deposition but didn’t alter platelet adhesion and aggregation (Fig 2).

  • Alteplase plus abciximab completely prevented clot formation (Fig 2).

Figure 2. A. Representative images of platelets and fibrin deposits after perfusion of untreated human blood and with abciximab, alteplase, or both. B. Platelet accumulation was quantified using the mean fluorescence (MFI) from a mosaic of 30 images per channel (left) and the same for fibrin formation (right). Results of MFI are expressed as arbitrary units, n = 3 duplicates per condition from three different healthy donors. *** P< 0.0001.

Other experiments in this study

The researchers retrospectively selected 21 individuals with immediate reocclusion from a registry of 929 AIS patients treated by MT for an intracranial anterior circulation large vessel occlusion (LVO). Immediately after the reocclusion, they administered abciximab intravenously.


Then, they performed clinical and radiological analyses to evaluate the primary and secondary outcomes. The primary outcome was the occurrence of a successful recanalization at the end of the MT procedure.


Main findings of these experiments

  • The rates of successful recanalization were significantly better in patients treated with abciximab than untreated reocclusion.

  • Potential intracranial hemorrhage (ICH) occurred in eight untread vs. five abciximab-treated reocclusion patients.

These results show that Glycoprotein IIb/IIIa antagonists are crucial in platelet aggregation and could be used as a rescue therapy in post-MT immediate reocclusion.


You can see more details of the study here.


How to get started?

Would you like to run similar experiments in your lab? This is the minimum experimental setup needed:

  • Vena8 Fluoro+ biochips – to mimic human blood vessels and model blood clots.

  • Mirus Evo pump – to control flow rates in the biochip. You may set the shear rate to model thrombosis in microcapillaries or other vessels.

  • Microenvironmental chamber – a temperature-controlled frame that keeps the biochip at 370C. The microenvironmental chamber sits on the microscope stage.

  • Inverted microscope – we supply the Zeiss AxioVert A1 with the VenaFlux Pro option or the Zeiss AxioObserver7 with the VenaFlux Elite option.

  • Digital camera – to capture images and video recordings. We supply the Prime BSI Express with both the VenaFlux Pro and Elite options. This is an excellent camera with a high frame rate suitable for thrombosis studies.

  • Image Pro Cell Analysis software – for your image and video analysis.

If you already have some of these items (such as the inverted microscope, camera, or cell analysis software), we recommend the VenaFlux Starter kit. We have options that suit all budgets. You can check them out on our eShop.


References






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