Key result
Computational simulations showed that higher tPA doses accelerated clot lysis at the expense of a substantial increase in the risk of intracerebral haemorrhage, while fine clots dissolved much more slowly than coarse clots.
Why the study?
Does higher tPA dose improve clot lysis without increasing the risk of intracerebral haemorrhage in a computational model of acute ischaemic stroke?
Does higher tPA dose improve clot lysis without increasing the risk of intracerebral haemorrhage in a computational model of acute ischaemic stroke?
Computational simulations demonstrate that while higher tPA doses accelerate clot lysis in acute ischaemic stroke, they disproportionately increase the risk of intracerebral haemorrhage by severely depleting plasma fibrinogen.
Warrants caution on higher tPA dosing in stroke models; leaves open clot structure effects and clinical validation.
Ischaemic stroke can occur when an artery to the brain is blocked by a blood clot. The use of thrombolytic agents, such as tissue plasminogen activator (tPA), to dissolve the occluding clot is limited by the risk of intracerebral haemorrhage (ICH), a known side effect associated with tPA. We developed a computational thrombolysis model for a 3D patient-specific artery coupled with a compartmental model for temporal concentrations of tPA and lysis proteins during intravenous infusion of tPA, in order to evaluate the effects of tPA dose on the efficacy of thrombolytic therapy and the risk of ICH. The model was applied to a 3-mm-long fibrin clot with two different fibrin fibre radii in the middle cerebral artery (MCA) - a setting relevant to ischaemic stroke, and results for different tPA dose levels and fibrin fibre radii were compared. Our simulation results showed that clot lysis was accelerated at higher tPA doses at the expense of a substantial increase in the risk of ICH. It was also found that a fine clot with a smaller fibre radius dissolved much slowly than a coarse clot due to a slower tPA penetration into the clots.
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Piebalgs et al. (2018) studied Acute Ischaemic Stroke. tPA (tissue plasminogen activator) vs. Different dose levels was evaluated on Clot lysis time and fibrinogen concentration. Computational simulations showed that higher tPA doses accelerated clot lysis at the expense of a substantial increase in the risk of intracerebral haemorrhage, while fine clots dissolved much more slowly than coarse clots.
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