Richard Buka
@richardbuka.bsky.social
200 followers 56 following 62 posts
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
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richardbuka.bsky.social
Wonderful! Thank you. Scots is such a fascinating thing to listen to - just a beautiful illustration of how new languages develop
richardbuka.bsky.social
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.
richardbuka.bsky.social
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...
richardbuka.bsky.social
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
richardbuka.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.
richardbuka.bsky.social
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...
richardbuka.bsky.social
Thanks to @profmakris.bsky.social for invitation and editorial input and thank you to insightful, thoughtful reviewers who helped to improve the piece substantially. #andexanetalfa
richardbuka.bsky.social
7/ I conclude - some patients likely to benefit but we don't know who they are - probably those treated early. At the moment, lack of evidence for net clinical benefit makes me sceptical of all the options available.
richardbuka.bsky.social
6/ Thrombosis rates are high with andexanet alfa - statistically increased risk of thrombosis vs usual care. No mortality or disability benefit was shown (study underpowered for these) so we cannot know if there is net benefit.
richardbuka.bsky.social
5/ However, the lack of blinding & usual care control --> bias especially in context of surrogate endpoints - particularly the need for rescue therapy (which was part of the primary outcome). Need for rescue therapy was significantly better with andexanet in whole cohort analysis
richardbuka.bsky.social
4/ With a usual care control arm, blinding patients and physicians is impractical - given different methods of administration for PCC and andexanet, and the chaotic, time pressured situation. These trials are hard enough to run and recruit to.
richardbuka.bsky.social
3/ I argue that the usual care control arm is reasonable as evidence for PCC is scanty and is not licensed for FXa DOAC reversal.
richardbuka.bsky.social
2/ 530 patients, most with intracerebral haemorrhage randomised to andexanet or usual care in ANNEXA-I. Showed improved haemostatic efficacy with andexanet - a surrogate endpoint composed of haematoma expansion <35% at 12h, need for rescue therapy and change in NIHSS <7.
richardbuka.bsky.social
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 🧵
richardbuka.bsky.social
Maybe the best option is going to be B-cell delivered FVIII gene therapy. Excited to see how this goes.
richardbuka.bsky.social
Making a mirror image of organisms doesn't sound like a good idea... Organisms made out of left handed DNA and right handed amino acids could evade our immune systems and have profound effects on the survival of life on earth.

www.science.org/doi/10.1126/...
Confronting risks of mirror life
Broad discussion is needed to chart a path forward.
www.science.org
richardbuka.bsky.social
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_...
richardbuka.bsky.social
They're planning on a pre-surgical trial against standard of care (which will be a messy control arm) so not going up against andexanet initially
richardbuka.bsky.social
Re antibodies, given it's a one off treatment for most, maybe not too worried although one would also worry about spreading of antibodies to endogenous FXa (although clearly unlikely and not seen with andexanet)
richardbuka.bsky.social
I think this is a promising agent but it's very different showing no thrombosis signals with d-dimer etc... than when you start giving it to real patients. The lack of effect on TFPI is reassuring though.
Reposted by Richard Buka
samelsonjones.bsky.social
#Ash24 #hemesky

Very large datasets suggest factor 12 haploinsufficiency substantially reduce venous #thrombosis.

Suggest intravascular pathological clot formation is molecularly different than extra vascular hemostatic clot formation?
Reposted by Richard Buka
isth.org
Abstract submission for #ISTH2025 is OPEN! Tag someone who should definitely submit an abstract below⏬
tomreiser.bsky.social
Abstract Submission for the #ISTH2025 Congress is now Open.
Deadline is January 15, 2025!
Don't miss showcasing your most exciting research and contribute to advancing the understanding of #thrombosis and #hemostasis on a global scale!
https://buff.ly/3B2XFQy
@ISTH-official.bsky.social #HemeSky
Reposted by Richard Buka
profmakris.bsky.social
A large prospective study from Austria shows that bleeding is more frequent and is of more relevance than generally assumed. Paper is behind a pay wall. tinyurl.com/2tf8kfv6 #cancer #bleeding
richardbuka.bsky.social
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.