George, We are a large public tertiary care hospital in West Tennessee. I am in the special coag lab. We are encountering some problems with patients coming in on dabigatran who need invasive stent procedures. Typically when the cardiologist uses heparin during the catheterization he orders an activated clotting time (ACT) post-procedure looking for a target ACT of 150 seconds. Of course, we are not achieving this with dabigatran patients. The cardiologists are ordering ACT’s every 4 hours to get to this target. We cannot support this type of request with personnel around the clock. Do you have any contacts that could help us with this issue? We are not sure what to do next since there is no literature to help us.
Regards, Emily Oakley, MT(ASCP)SH
Special Hematology/Special Coagulation
Medical Center Laboratory, Jackson, TN
Hello, Emily, and thank you for your question. Are these emergency patients who cannot be delayed the recommended 24 hours for dabigatran to clear? If so, choices are limited.
The ACT is a 1966 modification of the now obsolete Lee-White clotting time. Usually performed using semi-automated point of care equipment such as the Hemochron Signature Elite, the operator pipettes fresh whole blood into a cuvette containing the particulate activator celite and places the cuvette into the reaction well of the instrument. The instrument tilts the tube at regular intervals and detects and records the moment of clot formation. A typical reference interval is 100–150 seconds, though the range varies by institution.
The ACT monitors unfractionated heparin therapy up to 5 units/mL, thus the test is usually performed by the anesthetist in the cardiac catherization lab or operating suite, where cardiologists use 1–5 units/mL during the procedure. The ACT is the only test that accurately monitors heparin at these high doses. The cardiologist administers protamine sulfate at the conclusion of surgery to neutralize heparin, and monitors with the ACT to confirm the return to normal, <150 seconds. Once accomplished, the patient may continue to be monitored, if necessary, by the central laboratory using the partial thromboplastin time (PTT) or the anti-Xa heparin assay. The ACT is seldom performed in the central laboratory, but in Emily’s case, dabigatran slows the ACT return to normal so the patient continues to be monitored for up to 24 hours, long after the surgery is completed.
There exists no FDA-cleared method for monitoring dabigatran, though at least three are being readied for agency review, Aniara’s dilute thrombin time and Stago’s ecarin clotting time and ecarin chromogenic assay. Meanwhile, many laboratory directors are using the PTT as a semiquantitative estimate of direct thrombin inhibition. My recommendation is to compare and eventually substitute the in-lab PTT for the ACT until the patient returns to normal, or alternatively to adopt one of the new methods on the research use only basis. This would at least move these assays into the laboratory routine.
I wonder how often catheterization is performed while patients are on dabigatran. What have other institutions encountered?
Here is an article about clinical attempts at dabigatran neutralization and monitoring: