In silico representations of a subject's platelet phenotype successfully predicted blood function under flow at 200 and 1000/s wall shear rates, identifying patient-specific drug responses.
In silico representations of a subject's platelet phenotype can predict blood function under flow, potentially identifying patient-specific risks, drug responses, and novel genotypes.
During thrombotic or hemostatic episodes, platelets bind collagen and release ADP and thromboxane A(2), recruiting additional platelets to a growing deposit that distorts the flow field. Prediction of clotting function under hemodynamic conditions for a patient's platelet phenotype remains a challenge. A platelet signaling phenotype was obtained for 3 healthy donors using pairwise agonist scanning, in which calcium dye-loaded platelets were exposed to pairwise combinations of ADP, U46619, and convulxin to activate the P2Y(1)/P2Y(12), TP, and GPVI receptors, respectively, with and without the prostacyclin receptor agonist iloprost. A neural network model was trained on each donor's pairwise agonist scanning experiment and then embedded into a multiscale Monte Carlo simulation of donor-specific platelet deposition under flow. The simulations were compared directly with microfluidic experiments of whole blood flowing over collagen at 200 and 1000/s wall shear rate. The simulations predicted the ranked order of drug sensitivity for indomethacin, aspirin, MRS-2179 (a P2Y(1) inhibitor), and iloprost. Consistent with measurement and simulation, one donor displayed larger clots and another presented with indomethacin resistance (revealing a novel heterozygote TP-V241G mutation). In silico representations of a subject's platelet phenotype allowed prediction of blood function under flow, essential for identifying patient-specific risks, drug responses, and novel genotypes.
Flamm et al. (Fri,) conducted a other in Platelet function (n=3). Neural network model and multiscale Monte Carlo simulation vs. Microfluidic experiments was evaluated on Prediction of ranked order of drug sensitivity and clot size. In silico representations of a subject's platelet phenotype successfully predicted blood function under flow at 200 and 1000/s wall shear rates, identifying patient-specific drug responses.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: