ECMO is a therapy that’s becoming more and more common, particularly during the COVID-19 pandemic, as it’s often the only support therapy that will get some of these patients through when all conventional ARDS treatments have failed. ECMO involves the use of lots of plastic, catheters, pumps, oxygenators, etc. Blood traditionally doesn’t really like plastic, it often forms clots. So, typically, ECMO patients require some sort of systemic anticoagulation while they’re on the circuit.*
Unfractionated heparin as a continuous infusion has long been the mainstay of ECMO anticoagulation, but there are other options, including bivalirudin. Bivalirudin is a direct thrombin inhibitor (similar to dabigatran) that works by preventing the conversion of fibrinogen to fibrin (you knew that, I’m sure you have the clotting cascade memorized still, right?). It has a rapid plasma clearance, small volume of distribution, and elimination half-life of about 30 mins. All that means that it’s easy to titrate and you can usually just shut it off if there are bleeding problems. Also, it can’t cause heparin induced thrombocytopenia (HIT).
So, should we be using bivalirudin to anticoagulate all our ECMO patients? Well, in the interest of full disclosure, I’m a little biased. We use bivalirudin on all ECMO patients in our center.** We made that decision based on the overall safety of bivalirudin as compared to heparin, but another factor influenced that decision as well, COVID (doesn’t everything seem to come back to COVID these days?). In this case, our average ECMO run for patients who are COVID + is over 30 days. That amount of time presents lots of opportunities for bleeding issues and lots of opportunities for clotting issues (especially given the hypercoagulability of COVID patients). Ordinarily, if an ECMO patient develops clots in their circuit or oxygenator, while not ideal, it’s not the end of the world. You simply cut out the section of clotted circuit or exchange the oxygenator. However, with most patients with COVID, even a 30 second oxygenator exchange can see rapid desaturation, bradycardia, and peri-arrest (or actual arrest). So, it is a good idea to minimize the need for those. Additionally, the long ECMO runs require a lot of exposure to heparin, which increases the risk of developing HIT. HIT isn’t necessarily common, even in ECMO patients, but again, when it happens, it’s BAD.
The podcast ED ECMO, recently discussed this controversy with Ryan Rivosecchi, a pharmacist at University of Pittsburgh and lead author of a new study comparing heparin to bivalirudin. (You can read the original study here) They found a significant decrease in ECMO circuit events as well as decreased incidence of major bleeding in ECMO patients on bivalirudin as compared to heparin. They also discuss the potential cost differences in bivalirudin vs heparin, and, like lots of these things, it’s not as straightforward are the cost of one drug vs the other.
*Not all ECMO patients technically require systemic anticoagulation. Theoretically, if your flow rate is >5lpm on VV ECMO, the risk of significant clotting is low. At our center, we used to run VV ECMO quite frequently with no systemic anticoagulation. Also, shorter runs typically can avoid anticoagulation. VA ECMO can avoid this as well, but the stakes are higher. If a clot forms on VV and it embolizes, it’s going to get caught in the lungs, and well, you’re already on ECMO. But if a clot embolizes on VA, that’s a stroke. That’s bad. In the ED ECMO podcast linked above, Rivosecchi discusses this concept of “dry” ECMO and mentions an upcoming study at University Health Network in Toronto examining the feasibility of an “anticoagulation-free strategy” for VV ECMO.
**Again, not ALL. We have done a few short runs of ECMO with no anticoagulation even recently. However, these were done in patients without COVID and the associated hypercoagulability and in patients for whom systemic anticoagulation was contraindicated for some other reason.