1b) @AnticoagPharmD is Systems Director of Anticoagulation Services and also is the Co-Chair of the @NATF Thrombosis Medical Advisory Board & the @AnticoagForum ACE committee. She will be discussing the very exciting #CodeICH project that launched with https://t.co/wpT1bMdlsO
— cardio-met (@cardiomet_CE) March 18, 2024
1d) #CodeICH aims to protocolize these interventions, similar to current strategies used for the management of acute ischemic #stroke #AIS pic.twitter.com/J4Zos4U2SG
— cardio-met (@cardiomet_CE) March 18, 2024
3) Code ICH: A Call To Action
— cardio-met (@cardiomet_CE) March 18, 2024
Intracranial Hemorrhage #ICH is often devastating, & the rates of associated morbidity & mortality are high.
🚨Time is Brain. It is vital to have a pathway in place to provide aggressive early intervention & prevent 🧠deterioration. pic.twitter.com/cRWy09z9vu
5a) Quickly identifying the #ICH etiology will help guide tx. In the case of #anticoag associated #ICH, identifying the offending agent is critical to determining the optimal reversal strategy to support #hemostasis.
— cardio-met (@cardiomet_CE) March 18, 2024
6) Step 1⃣: determine if there is #anticoagulation on board. Just because it’s on the med list, doesn’t mean the patient is actually taking it.
— cardio-met (@cardiomet_CE) March 18, 2024
If the patient is unable to give an accurate med history, the following lab tests may be helpful 👇 pic.twitter.com/nLET65eIkL
8) In 2020 @JACC expert consensus provided a great outline on pt management for 🩸🩸.
— cardio-met (@cardiomet_CE) March 18, 2024
They highlight recommended #reversal strategies for:
– Warfarin
– Factor Xa Inhibitors
– oral DTIs.
Let’s take a deeper 👀into each pathway, starting with warfarin
🔓 https://t.co/5qhPaQ9Ems pic.twitter.com/0jE8YLcI91
9b) #Warfarin #reversal is focused on targeted replacement of Vitamin K-dependent #clottingfactors AND promoting synthesis of new clotting factors.
— cardio-met (@cardiomet_CE) March 18, 2024
As we saw earlier, warfarin inhibits Factors II, VII, XI & X, along with Protein C&S pic.twitter.com/aNudj5Es2k
10a) While the #4F #PCC is vital to rapidly decreasing the INR, IV Vit K is essential to sustaining it
— cardio-met (@cardiomet_CE) March 18, 2024
Have you heard about IV Vitamin K & anaphylactoid rxns?
Fun Facts:
– They are actually caused by the diluent (Castor Oil)
– Incidence 3:10,000
– Infuse slow over 30min to⬇️risk pic.twitter.com/u5caRVEcVx
10c) Each method has its Pros & Cons
— cardio-met (@cardiomet_CE) March 18, 2024
💡Variable Dosing
✅ More likely to achieve 🎯INR < 1.5 (May be important in #CodeICH situations)
❌ Delayed time to administration
vs
💡Fixed Dosing
✅Faster administration
✅Cheaper
❌Less likely to achieve INR < 1.5 w/o supplemental dosing
11a) No matter the dosing, the earlier you reverse, the better. Time is 🧠!
— cardio-met (@cardiomet_CE) March 18, 2024
In 2015 Schellinger et al. reported that reversing to a goal INR <1.3 + BP control in <4h was associated w/ significant ⬇️in hematoma expansion #HE &⬇️in-hospital mortality.
🔓 https://t.co/BJUZwMJsSz pic.twitter.com/tv0uRiIbD6
11c) At the end of the day, pick a strategy and stick with it . . . #Protocols are key & it is important to utilize clinical decision support at the time of order entry! pic.twitter.com/EpKmVFcIRp
— cardio-met (@cardiomet_CE) March 18, 2024
12b) Guidance to support either dosing option is listed below:
— cardio-met (@cardiomet_CE) March 18, 2024
👉 from @neurocritical & @SCCM: https://t.co/e0eXIAmbsc
👉 from @American_Heart: 🔓https://t.co/vaHdmoyaHD
👉from @ACCinTouch: https://t.co/5qhPaQ9Ems
12d) . . . but please KEEP IN MIND:
— cardio-met (@cardiomet_CE) March 18, 2024
🌟4F-PCC is SUPERIOR to FFP🌟#PCC is associated with
– Faster & more complete reversal
– Lower risk of volume overload
– Lower risk of infection
🔓 https://t.co/miWh3FFn4r
13b) However, we quickly woke up from that dream 😶🌫️when we realized that #DOAC-associated major bleeds are also associated with high rates of morbidity and mortality pic.twitter.com/oFLMf5a0YP
— cardio-met (@cardiomet_CE) March 18, 2024
14b) #Idarucizumab is a specific monoclonal antibody #MAb that adheres to and neutralizes #dabigatran at the thrombin binding site. It has no known off-target activity. pic.twitter.com/mc7vaDGv51
— cardio-met (@cardiomet_CE) March 18, 2024
15a) #REVERSE_AD: Study Info
— cardio-met (@cardiomet_CE) March 18, 2024
Design: Prospective open label
Population: 301 life threatening 🩸+ 202 emergent procedures
Intervention: 5g #Idarucizumab IV
Primary EP: Max % reversal of dilute thrombin time #dTT or Ecarin Clotting time #ECT in 4 h
🔓 https://t.co/XDsY3e8PyB pic.twitter.com/qJJOTr5y3Y
15c) #RE_VERSE AD: Adverse Events
— cardio-met (@cardiomet_CE) March 18, 2024
30 day ☠️13.5% (group A bleeders) & 12.6% (group B procedural)
90 day ☠️18.8% (group A) & 18.9% (group B)
Thrombotic events: 4.8% at 30 days and 6.8% at 90 days 🫀🫁🦵🧠 pic.twitter.com/03GPYot3TG
16a) Now it’s time to review the #reversal pathways for #FXaI: #Apixaban, #Rivaroxaban & #Edoxaban–the most commonly used #OACs for the treatment of #VTE & for #stroke prevention in #AFib
— cardio-met (@cardiomet_CE) March 18, 2024
Having a #protocol is essential to delivering high quality care in emergency situations pic.twitter.com/fzmLmPlkiM
17a) Here is another big debate 🥊. Does your #reversal agent matter? There are very strong opinions when it comes to which is best ⚔️
— cardio-met (@cardiomet_CE) March 18, 2024
Depending on where you practice you are either going to use #andexanet_alfa or #4F_PCC for the reversal of Major Bleeds in pts on FXa Inhibitors pic.twitter.com/IYfMTpGObH
17c) Clinical decision support #CDS at the time of order entry is critical to help avoid dosing errors and delays in care.
— cardio-met (@cardiomet_CE) March 18, 2024
Order entry questions can help providers differentiate between the approved Low and High Doses pic.twitter.com/bv8pR2zUNb
18a) #Andexanet: Ph 3⃣ Studies#ANNEXA_A: pts on #Apixaban 5mg BID x 3.5d#ANNEXA_R: pts on #Rivaroxaban 20mg Daily x 4d
— cardio-met (@cardiomet_CE) March 18, 2024
Patients: Healthy, older, non-bleeding
Primary Efficacy Measure: mean % change in anti-#FXa activity
🔓 https://t.co/mzeFhePIWR
18c) #ANNEXA_R
— cardio-met (@cardiomet_CE) March 18, 2024
26 patients received the HIGH 800mg Bolus + 8mg/min infusion
92% Reduction in aFXa activity
96% Thrombin Generation Restored w/in 2-5min
0 Thrombotic Events pic.twitter.com/22O3wtr2jv
20a) Then the much anticipated #ANNEXA_4 results were published
— cardio-met (@cardiomet_CE) March 18, 2024
Design: prospective, open label, single-group trial
N=352pts with acute major bleeding on #FXai
Primary Outcome: #Hemostasis within 12 hours after infusion
🔓 https://t.co/gBisLsQ5Um pic.twitter.com/yys3AM8SPZ
20c) 🔑 Baseline Characteristics:
— cardio-met (@cardiomet_CE) March 18, 2024
– Mean age 77
– Time to administration 4.7h
– #eGFR: <30mL/min 9%; 30-60mL/min 39%; ≥60mL/min 47%
– #AFib 80%, #VTE 17%, Other 3%
– Apix 55%, Riva 36%
– Bleed Site: #GI 26%, #ICH 64%, Other 10%
20e) ANNEXA-4 Final Results: #Efficacy
— cardio-met (@cardiomet_CE) March 18, 2024
🧪Median ⬇️ in aFXa activity
– 93% for Apixaban
– 94% for Rivaroxaban
⭐️Efficacy Outcomes
– Excellent or good hemostasis at 12h: 82% all bleeds; 80% in #ICH pic.twitter.com/aSXeNvFXPQ
20g) #ANNEXA_4 Final Thoughts:
— cardio-met (@cardiomet_CE) March 18, 2024
– #Andexanet provides rapid specific reversal of #FXa inhibition ➡️ excellent to good hemostatic control
– ⬇️aFXa activity:
o Predicted hemostatic efficacy #ICH
o Was associated w/ improved mortality in pts < 75yo (adj P=0.022; unadj P=0.003)
21a) And finally: #ANNEXA_I, about which you can LEARN & EARN more 🆓 CE/#CME at
— cardio-met (@cardiomet_CE) March 18, 2024
📓 https://t.co/bQ4qvD5Dzb
📓 https://t.co/lgW9NON4ff
both from expert author @Ash_Shoamanesh pic.twitter.com/JChVUYITHY
21c) #ANNEXA_I Patient Characteristics pic.twitter.com/InRG0rh5py
— cardio-met (@cardiomet_CE) March 18, 2024
21d) #ANNEXA_I Results pic.twitter.com/GrJER9zSK3
— cardio-met (@cardiomet_CE) March 18, 2024
21f) Now we are just waiting for someone to publish the full report pic.twitter.com/pzPSHiZCBF
— cardio-met (@cardiomet_CE) March 18, 2024
23a) So let’s discuss #4F_PCC
— cardio-met (@cardiomet_CE) March 18, 2024
– NOT FDA approved. Considered OFF Label for #FXai reversal
– Std dosing not been clearly defined (hence "usual care arms" are hard to interpret)
– Similar to warfarin reversal, we see Weight Based & Fixed Dosing
– Create a protocol & stick to it pic.twitter.com/qIryFv3x1o
23c) Other retrospective data not as positive. One review showed #andexanet ⬆️odds of achieving hemostatic efficacy v 4F-PCC* (85.8% vs 68.1%; OR 2.73; 95% CI 1.16-6.42) & odds of mortality (7.9% vs 19.6%; 0.36; 0.13-0.98)
— cardio-met (@cardiomet_CE) March 18, 2024
* ~80% received 25units/kg
🔓 https://t.co/ei0vfCllMk pic.twitter.com/UCXCYYl9IG
24) What about #ICH w/ #antiplatelets on board–ASA, #P2Y12, #GpIIb_IIIa Inhibitors?
— cardio-met (@cardiomet_CE) March 18, 2024
– No specific reversal agent
– Platelet Xfusion (not for #ticagrelor) +/- DDAVP may be considered for pts w/ICH or who need emergent surgery
– The dose of desmopressin is 0.3 mcg/kg IV x1 STAT
26a) If you are looking for resources to help get you started, check out:
— cardio-met (@cardiomet_CE) March 18, 2024
🚨@ACEPNow Guidance on #OAC Reversal in the ED
🩺Assess Patient: Labs, Imaging
🩹Initiate Supportive Care
🔁Emergent Reversal for Major/Life Threatening 🩸
🔓 https://t.co/AsfXgKzlT8
26c) … and The AC Forum Website also contains great resources for #reversal pathways and #AnticoagStewardship opportunities
— cardio-met (@cardiomet_CE) March 18, 2024
1666-2021-01-12-055939.pdf (https://t.co/0XCDgvTBYC) pic.twitter.com/fESrP2fhZR
28a) So what have you learned?
— cardio-met (@cardiomet_CE) March 18, 2024
Which reversal agent has been approved by @US_FDA for #ICH in patients treated with #rivaroxaban?
29b) The correct answer is b, as was seen in the recent @sheth_kevin-led analysis that @cardiomet_ce has featured. In addition, #ANNEXA_I has shown that early reversal makes #HE less likely (https://t.co/lgW9NON4ff).
— cardio-met (@cardiomet_CE) March 18, 2024
30) Congratulations! You just earned 1⃣ FULL HOUR 🆓 CE/#CME! Grab your certificate NOW at https://t.co/vLSktz5Kpl … and FOLLOW US for more #MedEd in the #cardiometabolic space! Thanks especially to content expert @AnticoagPharmD!
— cardio-met (@cardiomet_CE) March 18, 2024