Richard Buka
@richardbuka.bsky.social
Haem reg interested in thrombosis. Chair of HaemSTAR. Father of 3. Founder of pathquestionbank.com Blog: http://classicalcompass.substack.com. Pod: Don't Just Read the Abstract
The latest episode of Don't Just Read the Abstract with is now up!
We discuss the APPOINT-PNH trial of ictacopan, a proximal complement inhibitor and the first oral therapy for PNH.
Available now on all podcast platforms.
We discuss the APPOINT-PNH trial of ictacopan, a proximal complement inhibitor and the first oral therapy for PNH.
Available now on all podcast platforms.
March 9, 2025 at 7:48 PM
The latest episode of Don't Just Read the Abstract with is now up!
We discuss the APPOINT-PNH trial of ictacopan, a proximal complement inhibitor and the first oral therapy for PNH.
Available now on all podcast platforms.
We discuss the APPOINT-PNH trial of ictacopan, a proximal complement inhibitor and the first oral therapy for PNH.
Available now on all podcast platforms.
Hugely excited for this webinar from Saskia Middledorp lead on sooo many pivotal studies in H&T.
Part of HaemSTAR's research-focused 2 monthly webinar series hosted by the limbic
Tues 25th March 08:15 - 09:00 GMT.
thelimbic.com/uk/haematolo...
Part of HaemSTAR's research-focused 2 monthly webinar series hosted by the limbic
Tues 25th March 08:15 - 09:00 GMT.
thelimbic.com/uk/haematolo...
March 5, 2025 at 8:10 AM
Hugely excited for this webinar from Saskia Middledorp lead on sooo many pivotal studies in H&T.
Part of HaemSTAR's research-focused 2 monthly webinar series hosted by the limbic
Tues 25th March 08:15 - 09:00 GMT.
thelimbic.com/uk/haematolo...
Part of HaemSTAR's research-focused 2 monthly webinar series hosted by the limbic
Tues 25th March 08:15 - 09:00 GMT.
thelimbic.com/uk/haematolo...
Extremely interesting! Antibodies against COVID-19 receptor binding domain are also anti-PF4/heparin antibodies - frequently platelet activating. 1st report I know of showing this phenomenon. Well done to authors @versitiresearch.bsky.social, reviewers, & editors @bloodportfolio.bsky.social
February 7, 2025 at 6:14 PM
Extremely interesting! Antibodies against COVID-19 receptor binding domain are also anti-PF4/heparin antibodies - frequently platelet activating. 1st report I know of showing this phenomenon. Well done to authors @versitiresearch.bsky.social, reviewers, & editors @bloodportfolio.bsky.social
**NEW EPISODE**
Pleased to release the latest episode of Don't Just Read the Abstract with Pip Nicolson. We discuss Kuhne et al.'s study in @bloodportfolio.bsky.social on the treatment of TTP without the use of plasma exchange.
There will be a follow-up episode with an author interview.
Pleased to release the latest episode of Don't Just Read the Abstract with Pip Nicolson. We discuss Kuhne et al.'s study in @bloodportfolio.bsky.social on the treatment of TTP without the use of plasma exchange.
There will be a follow-up episode with an author interview.
February 3, 2025 at 7:04 PM
**NEW EPISODE**
Pleased to release the latest episode of Don't Just Read the Abstract with Pip Nicolson. We discuss Kuhne et al.'s study in @bloodportfolio.bsky.social on the treatment of TTP without the use of plasma exchange.
There will be a follow-up episode with an author interview.
Pleased to release the latest episode of Don't Just Read the Abstract with Pip Nicolson. We discuss Kuhne et al.'s study in @bloodportfolio.bsky.social on the treatment of TTP without the use of plasma exchange.
There will be a follow-up episode with an author interview.
Very cool study in @nature.com showing transfer of mutated mitochondria from cancer cells into tumour infiltrating T cells --> impaired T cell function and association with poor response to checkpoint inhibition.
www.nature.com/articles/s41...
www.nature.com/articles/s41...
January 28, 2025 at 7:58 PM
Very cool study in @nature.com showing transfer of mutated mitochondria from cancer cells into tumour infiltrating T cells --> impaired T cell function and association with poor response to checkpoint inhibition.
www.nature.com/articles/s41...
www.nature.com/articles/s41...
Pleased to share this perspective on andexanet alfa, now published in @rpth.bsky.social #openaccess🔓
rpthjournal.org/article/S2475-…
I cover blinding, surrogate endpoints, clinical outcomes and thrombosis.
A brief 🧵
rpthjournal.org/article/S2475-…
I cover blinding, surrogate endpoints, clinical outcomes and thrombosis.
A brief 🧵
January 7, 2025 at 9:49 AM
Pleased to share this perspective on andexanet alfa, now published in @rpth.bsky.social #openaccess🔓
rpthjournal.org/article/S2475-…
I cover blinding, surrogate endpoints, clinical outcomes and thrombosis.
A brief 🧵
rpthjournal.org/article/S2475-…
I cover blinding, surrogate endpoints, clinical outcomes and thrombosis.
A brief 🧵
Sitting at the front for the Ernest Butler prize lectures at #ASH24. Spent last 10 reading about this remarkable physician scientist who discovered G6PD deficiency, X inactivation, Gaucher disease, pioneered BMT and coded reference manager software
en.m.wikipedia.org/wiki/Ernest_...
en.m.wikipedia.org/wiki/Ernest_...
December 9, 2024 at 9:31 PM
Sitting at the front for the Ernest Butler prize lectures at #ASH24. Spent last 10 reading about this remarkable physician scientist who discovered G6PD deficiency, X inactivation, Gaucher disease, pioneered BMT and coded reference manager software
en.m.wikipedia.org/wiki/Ernest_...
en.m.wikipedia.org/wiki/Ernest_...
Thanks for reading. Check out Don't Just Read the Abstract podcast (on all major platforms). We have done a a two-part podcast on the ANNEXA-I trial.
November 28, 2024 at 6:20 PM
Thanks for reading. Check out Don't Just Read the Abstract podcast (on all major platforms). We have done a a two-part podcast on the ANNEXA-I trial.
Also, earlier data about andexanet showed thrombin generation being boosted to much higher than the baseline with andexanet. I wonder whether the TFPI effect is actually partly responsible for the effect on haematoma expansion - giving supranormal haemostasis.
November 28, 2024 at 6:20 PM
Also, earlier data about andexanet showed thrombin generation being boosted to much higher than the baseline with andexanet. I wonder whether the TFPI effect is actually partly responsible for the effect on haematoma expansion - giving supranormal haemostasis.
Andexanet definitely reverses anti-FXa activity - very well. And gives improved thrombin generation compared to PCC. But look at the TFPI effect - sustained for many many hours, and likely the cause for excess thrombosis.
November 28, 2024 at 6:20 PM
Andexanet definitely reverses anti-FXa activity - very well. And gives improved thrombin generation compared to PCC. But look at the TFPI effect - sustained for many many hours, and likely the cause for excess thrombosis.
Reasons? (1) Just statistical noise - mRS was a post-hoc analysis and study was not powered for this. (2) Andexanet may “delay” rather than prevent deterioration – think tortoise and hare – they end up in the same place (3) stroke risk offsetting benefit of ⬇️haematoma expansion.
November 28, 2024 at 6:20 PM
Reasons? (1) Just statistical noise - mRS was a post-hoc analysis and study was not powered for this. (2) Andexanet may “delay” rather than prevent deterioration – think tortoise and hare – they end up in the same place (3) stroke risk offsetting benefit of ⬇️haematoma expansion.
You can see that in responding patients with mRS 0-3 at presentation, andexanet patients were more likely than usual care patients to have a worse mRS at 30 days. The p-values are mine (Fisher's exact test) - and are a bit naughty given this is a post-hoc analysis.
November 28, 2024 at 6:20 PM
You can see that in responding patients with mRS 0-3 at presentation, andexanet patients were more likely than usual care patients to have a worse mRS at 30 days. The p-values are mine (Fisher's exact test) - and are a bit naughty given this is a post-hoc analysis.
So, whilst I agree that expansion is correlated with outcomes, it's not linear. Also, ANNEXA-I uses % change rather than absolute. There are issues relating to bleed volume etc... that I won't go into but long story short the stat above is a simplification.
November 28, 2024 at 6:20 PM
So, whilst I agree that expansion is correlated with outcomes, it's not linear. Also, ANNEXA-I uses % change rather than absolute. There are issues relating to bleed volume etc... that I won't go into but long story short the stat above is a simplification.
This is based on Delcourt et al. 2012 – a subanalysis of the INTERACT1 study - so these are hypertensive patients who are not anticoagulated. In this study, haematoma expansion was measured at 24h rather than 12.
November 28, 2024 at 6:20 PM
This is based on Delcourt et al. 2012 – a subanalysis of the INTERACT1 study - so these are hypertensive patients who are not anticoagulated. In this study, haematoma expansion was measured at 24h rather than 12.
Data not new but Kaplan Meier is useful. All cause mortality: 28% vs 26%, death due to index bleeding event: 5% vs 7%
Many point out that 30 days is too short to look for survival effects of acute interventions but this is all we have to go on.
Many point out that 30 days is too short to look for survival effects of acute interventions but this is all we have to go on.
November 28, 2024 at 6:20 PM
Data not new but Kaplan Meier is useful. All cause mortality: 28% vs 26%, death due to index bleeding event: 5% vs 7%
Many point out that 30 days is too short to look for survival effects of acute interventions but this is all we have to go on.
Many point out that 30 days is too short to look for survival effects of acute interventions but this is all we have to go on.
First AZ presented (mostly) published trial data. Andexanet showed significant improvement in all parameters making up haemostatic efficacy but the only significant component was haematoma expansion. The visual representation is quite useful but nothing new here.
November 28, 2024 at 6:20 PM
First AZ presented (mostly) published trial data. Andexanet showed significant improvement in all parameters making up haemostatic efficacy but the only significant component was haematoma expansion. The visual representation is quite useful but nothing new here.
Thrombosis rates are much higher in patients receiving high dose andexanet (as are death rates - more on efficacy in next thread)
November 25, 2024 at 11:03 PM
Thrombosis rates are much higher in patients receiving high dose andexanet (as are death rates - more on efficacy in next thread)
Patients with history of heart failure, stroke or MI are at particularly high risk of thrombotic events.
November 25, 2024 at 11:03 PM
Patients with history of heart failure, stroke or MI are at particularly high risk of thrombotic events.
Interestingly, thrombosis rate in patients who did not receive any haemostatic treatment had a high thrombosis rate – 4/33 (12.1%) vs 11/232 (4.8%). May just be statistical noise or could be related to thrombotic risk factors and reasons why physicians did not give anything.
November 25, 2024 at 11:03 PM
Interestingly, thrombosis rate in patients who did not receive any haemostatic treatment had a high thrombosis rate – 4/33 (12.1%) vs 11/232 (4.8%). May just be statistical noise or could be related to thrombotic risk factors and reasons why physicians did not give anything.
In case you’re wondering – as expected rate of oral anticoagulation restart was low – ~10% by day 30 – might reflect treatment of patients with thrombotic events.
November 25, 2024 at 11:03 PM
In case you’re wondering – as expected rate of oral anticoagulation restart was low – ~10% by day 30 – might reflect treatment of patients with thrombotic events.
At the 5-day mark, only 50% patients were on some kind of anticoagulation. This is probably reasonable as we know that 81% patients were mRS 0-3 at baseline (moderate disability) so a good proportion should be able to mobilise.
November 25, 2024 at 11:03 PM
At the 5-day mark, only 50% patients were on some kind of anticoagulation. This is probably reasonable as we know that 81% patients were mRS 0-3 at baseline (moderate disability) so a good proportion should be able to mobilise.
Could thromboprophylaxis, prevent thrombotic events after andexanet? Firstly, I would not expect LMWH to prevent ARTERIAL events. Nevertheless, AHA guidelines recommend thromboprophylaxis in non-ambulatory patients after 1-4 days (2015 guideline), and 24-48h (2022 guideline).
November 25, 2024 at 11:03 PM
Could thromboprophylaxis, prevent thrombotic events after andexanet? Firstly, I would not expect LMWH to prevent ARTERIAL events. Nevertheless, AHA guidelines recommend thromboprophylaxis in non-ambulatory patients after 1-4 days (2015 guideline), and 24-48h (2022 guideline).
To my mind, NOPE! The reason we see this pattern is because the events caused by andexanet happen really early - median 3.5 days vs 16 days with usual care. With andexanet, 17/35 events were in the first 3 days vs 1/16 with usual care.
November 25, 2024 at 11:03 PM
To my mind, NOPE! The reason we see this pattern is because the events caused by andexanet happen really early - median 3.5 days vs 16 days with usual care. With andexanet, 17/35 events were in the first 3 days vs 1/16 with usual care.
AZ presented striking data on thrombotic events and re-anticoagulation (refers to thromboprophylaxis). Suggests that if you give thromboprophylaxis, you can prevent andexanet-induced events. Is this correct?
November 25, 2024 at 11:03 PM
AZ presented striking data on thrombotic events and re-anticoagulation (refers to thromboprophylaxis). Suggests that if you give thromboprophylaxis, you can prevent andexanet-induced events. Is this correct?
FDA's own review of thrombotic events reported 12 extra cases – 9 in andexanet & 3 in usual care – that were not assigned as thrombotic by blinded committee. Sorry, I don’t have more info on this!
Final figures (based on n=471 FDA safety set): 14.6% vs 6.9%, stroke 5% vs 0.4%.
Final figures (based on n=471 FDA safety set): 14.6% vs 6.9%, stroke 5% vs 0.4%.
November 25, 2024 at 11:03 PM
FDA's own review of thrombotic events reported 12 extra cases – 9 in andexanet & 3 in usual care – that were not assigned as thrombotic by blinded committee. Sorry, I don’t have more info on this!
Final figures (based on n=471 FDA safety set): 14.6% vs 6.9%, stroke 5% vs 0.4%.
Final figures (based on n=471 FDA safety set): 14.6% vs 6.9%, stroke 5% vs 0.4%.