| dc.description.abstract | Bleeding and thrombosis episodes in children are often encountered during ECMO/VAD. Pediatric patients on ECMO are known to have compromised platelet function and depleted plasma factors, making them susceptible to bleeding when anticoagulated with heparin. More concerning is the fact that hematology tests (ACT, aPTT, Anti-Xa) often report positive even when bleeding risk is present. TEG and ROTEM do provide greater information about whole blood coagulation, however a major deficiency with these tests is that they measure clotting characteristics under conditions that are not physiologically-relevant, thus limiting their ability to assess platelet function. To overcome these limitations, we developed a rapid and ultra-low volume tortuosity-activated microfluidic device for whole blood coagulation monitoring in pediatric critical care patients.
The microfluidic device contains channels made of soft lithography that mimics a stenosed arteriolar blood vessel network and incorporates bio-rheological parameters known to induce clot formation such as blood vessel tortuosity and shear gradients. When the device is connected to a pressure sensor and whole blood is perfused it provides a tool to quantitatively determine clotting time. We demonstrate that the clotting times increase when clinically-relevant doses of heparin and bivalirudin is added to healthy blood samples. In addition, we validate these measurements by showing fluorescent images of that fibrin inhibition. Furthermore, we found that the clotting times were similar for devices coated with rat or human collagen, yet significantly different for horse collagen treated devices. Also, we saw that clotting time is dependent on platelet count. Lastly, we did not measure any microchannel occlusion when the device was treated with blood from pediatric ECMO patients. We then found that this lack of occlusion is due to poor platelet adhesion. We test if platelet adhesion can be restored with the addition of von Willebrand factor (VWF). | |
