Extracorporeal Liver Assist Device (ELAD) was shown to cause thrombocytopenia in clinical trials. Obviously, this is an unwanted side effect and could worsen the already compromised hematological state of liver failure patients. Can someone explain why this is occurring? (Osmolarity imbalance between blood cells and ELAD cells/solutions?; Improper channel size, causing cell membrane damage or blood cell sequestration?)
Papers would be welcomed as responses also.
https://www.youtube.com/watch?v=vND7zrTLy88
I will say the tubing and large surface area may contribute to it. It may be like Kasabach-Merritt Syndrome happens inside the ELAD.
Dear Joseph,
I agree with Teng, but there is another issue that must be considered. Since the normal liver inactivates coagulation factors, one possibility is that increased levels of activated coagulation factors would cause platelet adhesion.
Silvia may have a point but the reason I did not put it down was the fact that the system will be primed with anticoagulant and the material of the circuit usually is treated.
Can either of you think of a theoretical workaround? Smaller diameter tubing? Redesign of the cell cartridges? Multiple inflow channels with one outflow?
If it is a problem of platelet adhesion, how would you counteract this without compromising clotting ability within the patient?
I am not working on this topic so realy can not provide any good idea. But, artificial liver based on stem cells have been studied recently. I will encourage young scientists to work on it.
Joseph, I need more data. Are the platelets large or normal? Take a look in http://mmserver.cjp.com/images/image/0144076.jpg
At five hours, there are two normal-size platelets. The others are macrothrombocytes. The coulter may not identify macrothrombocytes as platelets, but a technician or a hematologist can help you with the information. More important than platelet count are the clinical consequences. What happens with these patients? Does thrombocytopenia caused by ELAD increase the risk of bleeding?
I need to find the original study results, because all the speaker said was that the device produced a temporary thrombocytopenia that relented after ELAD therapy was discontinued. Will try to find that ASAP.
As for clinical consequences, they did not report any serious adverse effects from the thrombocytopenia, though with more critical patients (MELD >30) the hematological insult isn't appreciated by the attendings. When I broached the subject to the Hepatology clinical team, they didn't feel that it was worth the risk.
I bet you will be able to find the blood slides of the patients. In this case, it would be very helpful to review them in order to see if they are large or normal-size platelets.
I don't think we know, but I assume it is related to platelet adhesion to tubing. The charcoal column used in early studies most likely had non-specific adhesion (resolved by switching to plasma perfusion). I don't think turbulence plays a role. Long-term use of heparin is a theoretical concern, but we did not see HIT in 23 patients treated with whole blood perfusion.
Patients with acute liver failure are hypercoaguable despite the disturbances in standard standard coagulation tests - clotting in the device will cause depletion of clotting factors (including platelets) with limited ability to replace them.
I hope that helps
Thank you all for your answers. I certainly have more research to do on these devices to think up some work-arounds for these and other problems.
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