2) The outstanding faculty for this course included Thorsten Steiner (chair), Michiel Coppens, and Adrian Parry-Jones @adrianpj1. This #tweetorial recaps the questions directed to the faculty by the learned audience at the #ESOC22 presentation. pic.twitter.com/r4j2fpfAa2
— cardio-met (@cardiomet_CE) December 12, 2022
4) The program at #ESOC22 was a case-based discussion of the challenges of managing #ICH in patients taking #DOACs that inhibit #Factor_Xa. The combination of #anticoagulation and #ICH creates clinical problems and poor outcomes! pic.twitter.com/ZNLx4gmpVu
— cardio-met (@cardiomet_CE) December 12, 2022
6) The magnitude and pace of #hematoma expansion in ICH is a key determinant of neurologic recovery and #mortality. Anticoagulation, understandably, makes expansion more likely, more rapid, and more severe. pic.twitter.com/IQVbqJIAUx
— cardio-met (@cardiomet_CE) December 12, 2022
8) See previous tweetorials (still available for credit) from @rkchoi & @caseyalbin (https://t.co/ODUtDv2a5B) and from @namorrismd (https://t.co/ewU526Mneb) for evidence and guidance on management of these pts with specific factor reversal vs nonspecific factor repletion.
— cardio-met (@cardiomet_CE) December 12, 2022
10a) The faculty responded: There is no "gold standard" for #reversal of #anticoagulation in such cases. While other approaches such as #4F_PCC, #rFVIIa, and even #cryopreciptate have been reported and discussed, none has been approved for reversal of #apixaban or #rivaroxaban.
— cardio-met (@cardiomet_CE) December 12, 2022
10c) The @US_FDA therefore approved the design of a single-arm study, as given the existing evidence, withholding a treatment supported by biologic rationality and supporting data would not be ethical.
— cardio-met (@cardiomet_CE) December 12, 2022
10e) Meanwhile, #andexanet remains the only #FDA-approved treatment for reversal in these patients. Although #4F_PCCs may be usual care in some hospitals, supporting data currently are of a low quality of evidence.
— cardio-met (@cardiomet_CE) December 12, 2022
11) Next question: "Why do we see thromboembolic events after reversal of anticoagulation?" See data from #ANNEXA-4: pic.twitter.com/AN4wEMlQix
— cardio-met (@cardiomet_CE) December 12, 2022
12b) In the #ANNEXA-A/R studies in healthy volunteers, no thrombotic events occurred (see 🔓https://t.co/mzeFhePIWR). In ANNEXA-4 study in bleeding patients, there were no thrombotic events after the restart of oral anticoagulation (🔓https://t.co/g6TXQgMf4i).
— cardio-met (@cardiomet_CE) December 12, 2022
12d) This concept is further supported by the occurrence of #thromboembolic complications after treatment of aFXa-#OAC-associated bleeding with #PCC. In a retrospective study of 333 pts (184 on warfarin, 48 on rivaroxaban) who received 383 PCC doses for bleeding . . .
— cardio-met (@cardiomet_CE) December 12, 2022
12f) There was increased rivaroxaban use in patients who developed thrombosis (25.4% vs 12.2%; P = .011), and a higher rate of TEC in those who received >1 dose of PCC (21.8% vs 7.9%; P = .002). pic.twitter.com/NpiYuZk1nH
— cardio-met (@cardiomet_CE) December 12, 2022
14a) The faculty respond: #Andexanet has been shown to bind & hinder #TFPI, the first line of inhibitor of blood coagulation. TFPI can reversibly inhibit #FXa. Therefore this could be a mechanism by which andexanet use could contribute to thrombosis in the aFXa-treated pt.
— cardio-met (@cardiomet_CE) December 12, 2022
14c) The #andexanet_alfa–#TFPI interaction appears to have only a small effect on thrombin generation, which affects only the extrinsic (not intrinsic) coagulation pathway. See 🔓https://t.co/nrKdQCaXil.
— cardio-met (@cardiomet_CE) December 12, 2022
16a) The faculty responds: It is correct that the #ANNEXA studies enrolled only patients with aFXa-#DOAC-related hemorrhage, and did not include pts treated with DOACs but not bleeding and requiring surgery.
— cardio-met (@cardiomet_CE) December 12, 2022
16c) In the case presented by Coppens, however, a pt with acute #ICH on #DOAC #anticoagulation was reversed with #andexanet, but went on to deteriorate and require surgical evacuation. Initial administration was consistent with label, and the surgeons in the case . . .
— cardio-met (@cardiomet_CE) December 12, 2022
17) The symposium continues to be available for viewing and #CME credit, but YOU 🫵 can now pick up an additional 0.5h credit by clicking to https://t.co/tvkoGpJIDV. Please take full advantage of this opportunity as we reach the end of the year 📅and you need that credit!
— cardio-met (@cardiomet_CE) December 12, 2022