Abstract
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.
Highlights
The efficacy of thrombolytic therapy depends on many factors; these include the location, size and composition of the clot, blood flow regime around the clot and drug dose
This was the procedure adopted in the NINDS clinical trial[6] which led to the FDA approval and wide-spread adoption of thrombolytic therapy for ischaemic stroke
The model of Godfrey et al.[17] used three compartments to describe the pharmacokinetics of tissue plasminogen activator (tPA), reactions in the plasma were not included unlike the models of Noe & Bell[18] and Tiefenbrunn et al.[19]
Summary
Andris Piebalgs[1], Boram Gu1, Dylan Roi[2], Kyriakos Lobotesis[2], Simon Thom3 & XiaoYun Xu 1. 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. We present a computationally efficient model that can evaluate clot lysis patterns for a given therapeutic regimen in a patient-specific geometry reconstructed from CT scans This is achieved by coupling a 3D thrombolysis model with a compartmental model that describes the temporal evolution of lysis proteins in plasma during intravenous infusion of alteplase. The lysis of a 3-mm-long fully occluding clot in the M1 segment of the middle cerebral artery (MCA) of an 80 kg man is used as an example to evaluate the effect of tPA dose on the efficacy of thrombolytic therapy. The latter is based on findings that low levels of fibrinogen concentration in plasma are associated with increased risk of ICH20,21
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
