Yes, join here Tuesday for CE/#CME for a review of antithrombotic reversal by expert author @md_pollack. Check it out, @CardioNerds @beaverspharmd @SnayCardsPharmD @johneikelboom @VerhammePeter @CMichaelGibson @AlexSpyropoul @connors_md @brian_hiestand @ToddVillinesMD @TheMahaf
— cardio-met (@cardiomet_CE) September 20, 2021
2) This educational platform is supported by grants from AstraZeneca, Bayer, Chiesi, and NovoNordisk, and is intended for healthcare professionals. Follow this thread for credit from @academiccme. Here’s a case:
— cardio-met (@cardiomet_CE) September 21, 2021
4) Now, let’s get this straight. This is NOT a #neurosurgery #tweetorial. We won’t talk about how best to manage this pt from that perspective. Suffice it to say she is neither unstable nor moribund. We are here to talk about #hemostasis.
— cardio-met (@cardiomet_CE) September 21, 2021
6) C: She also has #CAD and had a #drugelutingstent placed 5 weeks ago. She is on #clopidogrel. D: Same #PCI history but she is taking ticagrelor. So let’s review some basics about #antithrombotics and #bleeding. First, these agents don’t CAUSE spontaneous bleeding . . . pic.twitter.com/KQNYmru64Y
— cardio-met (@cardiomet_CE) September 21, 2021
8) . . . in this case means doing all we can to limit hematoma expansion and permanent neurologic impairment or even death 🪦. So we want to TURN OFF the antithrombotic activity of the #DOAC or #P2Y12i at play in each scenario. Doing so makes overall mgt easier.
— cardio-met (@cardiomet_CE) September 21, 2021
10) . . . whether FIIa, FXa, or the platelet P2Y12 receptor, to once again meaningfully participate in hemostasis. REPLETION means we try to overwhelm the blocker by giving the patient more of what is being blocked–i.e., coagulation factors or fresh platelets.
— cardio-met (@cardiomet_CE) September 21, 2021
12) . . . EMERGENCY 🏥 treatment of severe, on-going, or life-threatening bleeding. In the #ICH patient like ours who is not moribund, reversal would be indicated almost always, whether pt is destined for surgery or not.
— cardio-met (@cardiomet_CE) September 21, 2021
14) Mark your answer and return tomorrow for the answer and more discussion! You’re on your way to free CE/#CME. Follow us! @CNCFCardio @GBarnesMD @SABOURETCardio @BartoszHudzik @dr_benoy_n_shah @ValleAlfonso @traceymtay @HollyEHinson @Cardio_delaGuia @JTLLERGO @Rx_Ed
— cardio-met (@cardiomet_CE) September 21, 2021
16) Quick recap: 65F with survivable #ICH complicated by her treatment with #dabigatran. She needs multimodal management that includes #idaucizumab–the specific REVERSAL agent for dabigatran. It's a fully humanized monoclonal antibody directed specifically at dabigatran.
— cardio-met (@cardiomet_CE) September 22, 2021
18) RE-VERSE AD was an open-label single-cohort study of idarucizumab in pts on dabi with major/life-threatening bleed. Not ethical to compare to placebo and no gold standard for a comparator. What lacked in design rigor was made up for in results (N Engl J Med 2017; 377:431-441)
— cardio-met (@cardiomet_CE) September 22, 2021
20) The patient stills needs intensive care to minimize brain damage. Same would apply in a GI bleed or a trauma victim on dabi: idarucizumab does NOT plug holes! Fortunately, it also appears to have NO prothrombotic effect of its own, and no significant safety concerns!
— cardio-met (@cardiomet_CE) September 22, 2021
22) Andexanet works differently from idarucizumab, and I mean besides it working only for anti-FXa drugs and not dabigatran. It's not an antibody, it's an inactive Factor Xa lookalike that attracts the inhibitor off of native FXa so normal hemostasis can resume.
— cardio-met (@cardiomet_CE) September 22, 2021
24) open-label, no comparator. Majority of bleeds were #ICH like our pt. Figure below shows efficacy, with marked ⬇️ of anti-FXa activity. 82% of patients had excellent or good hemostatic efficacy at 12h, as adjudicated according to prespecified criteria. Higher incidence . . . pic.twitter.com/7rKRDvXwNO
— cardio-met (@cardiomet_CE) September 22, 2021
26) Clinical uptake has not been as rapid as expected (and andexanet is still not approved 🇨🇦), but that's at least in part due to price. That absence of widespread availability of the specific reversal agent has led to use of a REPLETION strategy for anti-FXa ICH with
— cardio-met (@cardiomet_CE) September 22, 2021
28) Welcome back! You're nearing the conclusion (and credit grab) of our #tweetorial on reversal of #antithrombotic therapy in the #bleeding patient. I'm @md_pollack and you have found the only source of accredited, serialized tweetorials in #cardiometabolic medicine! #FOAMed
— cardio-met (@cardiomet_CE) September 23, 2021
30) . . . reversal of VKAs, so they contain the vitamin K-dependent factors (II, VII, IX, and X), the anticoag proteins C & S (some also contain antithrombin), & small amounts of heparin. For treatment of VKA-related bleed, PCCs are consider superior to #FFP.
— cardio-met (@cardiomet_CE) September 23, 2021
32) The use of PCCs in such pts indeed might tip the hemostatic balance ➡️hypercoagulability & might be assoc'd w/ ⬆️ thrombotic events. And of course these pts usually have an ⬆️ background risk of thromboembolism–hence the Rx for anti-FXa therapy in the first place.
— cardio-met (@cardiomet_CE) September 23, 2021
34) . . . a low risk of post-repletion thrombotic events & has similar efficacy to that for VKA reversal. 4FPCC (Kcentra, Beriplex P/N, Octaplex) can be dosed at 2000u OR a weight-based dose of 25-50u/kg. Some guidelines rec #rFVIIa for DOAC reversal, but only if . . .
— cardio-met (@cardiomet_CE) September 23, 2021
36) So let's close with a quick look at Scenarios 3 & 4. Recall (a) that we are talking about an #ICH in a 65F who also has #CAD and has a recent #stent. She is taking a #P2Y12i. A momentary return to basics: the P2Y12 receptor on the platelet is the binding site for ADP . . .
— cardio-met (@cardiomet_CE) September 23, 2021
38) Because clopidogrel irreversibly inhibits #platelets, standard practice in clopidogrel-associated #ICH is to give platelet transfusions. New platelets should quickly outstrip the binding capacity of circulating clopidogrel. As with anticoags, tho, platelet REPLETION . . .
— cardio-met (@cardiomet_CE) September 23, 2021
40) . . . still to overcome, because the ticagrelor can jump off bound platelets and bind the new ones. Enter a new potential approach–REVERSAL for a P2Y12i. Currently in Ph 3, #bentracimab (the artist formerly known as #PB2452) . . .
— cardio-met (@cardiomet_CE) September 23, 2021
42) . . . the P2Y12i effects of ticagrelor to return platelet response to ADP to normal. The Ph 1 study is at @DLBHATTMD @md_pollack et al, https://t.co/ReAEVOmO7j and you can learn more about it and earn even MORE FREE CE/#CME (1.0 hr) at https://t.co/CW2wmrwLwu.
— cardio-met (@cardiomet_CE) September 23, 2021
44) That’s it! You made it! FREE CE/#CME! #physicians #nurses #pharmacists make your way to https://t.co/psCb4DJWtg for 0.5h credit, applicable 🇺🇸🇨🇦🇬🇧🇪🇺. And FOLLOW US so as not to miss next week’s accredited #tweetorial! pic.twitter.com/OXhkHRTQtB
— cardio-met (@cardiomet_CE) September 23, 2021