10 Posts Not to Miss This Week

This week brings a striking mix of new evidence and therapeutic advances across hematology, hemostasis, thrombosis and cardiovascular medicine.

From new anticoagulation strategies and advances in factor replacement to emerging treatments for ITP and myeloproliferative neoplasms, several posts highlight how established approaches are being challenged – and, in some cases, redefined.

At the same time, evolving evidence in pulmonary embolism, ischemic stroke and high-bleeding-risk coronary intervention underscores a central theme in modern medicine: finding better ways to prevent thrombosis without compromising safety.

Beyond the clinic, structural insights into coagulation proteins and new perspectives on Factor IX manufacturing illustrate how discoveries at the molecular and translational level continue to shape therapeutic innovation.

Here are 10 posts worth catching up on this week – from changing standards of care and newly approved therapies to emerging evidence that may influence how we approach bleeding and thrombosis in the years ahead.

Maria Queralt Gorgas, Director of Pharmacy Services at Vall d’Hebron Barcelona Hospital Campus:

“Anticoagulation for Atrial Fibrillation with Intermediate Stroke Risk, New England Journal of Medicine.”

Thirunavukkarasu Angappan, Vice President of Operations and Manufacturing at PopVax:

“BeneFIX Is Recombinant. Mononine Isn’t. Hemophilia B Patients Still Need Both on the Shelf.

Every vial of plasma-derived Factor IX carries a bit of thousands of different donors in it.

Every vial of recombinant Factor IX, like BeneFIX, comes from just one carefully chosen cell line grown in a lab.

• Plasma-derived products pool thousands of donors into each batch, which means small differences — in sugar structures on the protein, in donor variation — that manufacturers have to control for every single time.
• Recombinant products come from one fully characterized cell bank. RIXUBIS, for example, is made in a CHO (Chinese hamster ovary) cell line and doesn’t use any human or animal material in its manufacturing. There’s still some batch-to-batch variation even here, but it’s the kind you can select for and control upfront, not something that changes with every new donor pool.
• Recombinant Factor IX keeps growing its market share — about 6 to 9 percent a year — largely because that kind of control is easier to build a process around.
  But here’s where it gets more interesting than ‘manufacturing wins’.

Plasma-derived and recombinant Factor IX actually work equally well for normal bleed prevention and treatment — that’s well established.

The real complication shows up with inhibitors.

Hemophilia B inhibitors are rare, about 1 to 3 percent of patients, but when they happen, they bring a real risk that Factor VIII inhibitors don’t carry the same way — anaphylaxis, and sometimes kidney complications like nephrotic syndrome, and this can happen whether the product is plasma-derived or recombinant.

Trying to build immune tolerance in these patients is much harder and riskier in hemophilia B than in hemophilia A, with fairly unpredictable success.

So for these patients, doctors usually don’t just give more Factor IX of either kind — they turn to bypassing agents instead.

I’ve spent my career validating both mammalian cell platforms and reviewing plasma product quality systems, and here’s my honest read: the case for keeping plasma-derived Factor IX around isn’t about it being clinically better for any one group of patients.

It’s about keeping supply steady, keeping costs manageable, and making sure patients in places where recombinant supply isn’t always reliable still have a treatment option.

As recombinant manufacturing keeps scaling up, does plasma-derived Factor IX still have a real clinical reason to stick around — or does it end up being mainly a backup option for less-resourced healthcare systems?“

Ahmed Kotb, Head of Global Oncology Medical Affairs at Daiichi Sankyo:

“For ITP plus critical or life-threatening bleeding plus platelets less than 20×10⁹/L:

• High-dose IVIG.
• High-dose corticosteroids.
• Platelet transfusion.
• Tranexamic acid.
• Consider early TPO-RA.
• If bleeding remains uncontrolled – consider urgent splenectomy.

Avoid routine rFVIIa because of thrombosis risk.“

Ruben Mesa, President of Cancer National Service Line at Advocate Health:

“Honored to have been involved with (as PI of the Global Surpass ET trial) the now FDA approval of ROPEG INF a2b for patients with Essential Thrombocythemia.

This is the first approval in over 30 years for patients with this myeloid neoplasm MPN and helps decrease disease associated risks, symptoms, and modifies the underlying clone.“

Kelly Anderson, Healthcare Expert:

“Recognizing vascular complications early is critical, particularly when underlying hematologic and vascular conditions may increase the risk of impaired circulation and thrombosis.”

Kavya Keerthana, Hematologist at Prime Health:

“A potentially important advance in Polycythemia Vera (PV).

In PV, excess red blood cells increase the risk of blood clots, stroke and heart attack.

For years, regular phlebotomy has been a cornerstone of treatment—but repeated blood removal can also lead to iron deficiency.

The FDA has approved rusfertide, a hepcidin mimetic that offers a different approach by regulating iron availability and reducing excessive red blood cell production.

In the Phase 3 VERIFY trial, 76.9 percent of patients receiving rusfertide achieved clinical response, with fewer phlebotomies and improvements in symptoms such as fatigue.

A fascinating shift in how we think about managing PV.“

Josef Kroupa, Interventional Cardiologist, Healthcare Consultant:

“Czech cardiology at the forefront.

Today, at the Congress of the European Society of Cardiology, we presented to the international cardiovascular community the results of the largest randomized trial to date investigating interventional treatment of acute pulmonary embolism (PRAGUE-26).

At the same time, its results are being published in The New England Journal of Medicine (NEJM) — marking the first original Czech study in history to be published in the journal.

Behind this study are years of hard work, an extraordinary team effort, and above all, a shared ambition to change the way this serious disease is treated worldwide.

A heartfelt thank you to everyone who has been part of this journey.

And yes — we did it!“

Nadezhda Vasilyeva, Neurologist:

“The boundaries of acute ischemic stroke management are shifting: the 2026 AHA/ASA guidance allows tenecteplase 0.25 mg/kg as an alternative to alteplase within 4.5 hours or less; concurrently, trials (e.g. HOPE) are investigating selective thrombolysis expansion to 4.5-24 hours using perfusion-based selection.

Antithrombotic management after reperfusion remains a trade-off: ATIS‑NVAF data showed increased bleeding without clear clinical benefit when combining anticoagulants and antiplatelets.

The emergence of Factor XIa inhibitors (e.g. asundexian; Phase III OCEANIC‑STROKE) shows reduced recurrence with an acceptable bleeding profile – potentially addressing a key neuro-safety dilemma.

As a clinician with 5 plus years in neurology, I translate this bedside experience into rigorous ICH‑GCP safety monitoring.

Colleagues in research teams – how are you adapting monitoring systems for extended thrombolysis windows and new antithrombotic combinations?“

Stefano Garzon, Interventional Cardiologist, PhD candidate:

“SELUTION DeNovo HBR: weren’t HBR patients supposed to bleed more with DES?

SELUTION DeNovo (NCT04859985) randomised 3,323 patients with de novo coronary lesions to a sirolimus-eluting balloon strategy with provisional stenting or to systematic DES.

The HBR substudy (Rissanen et al., EuroInterventio 2026, doi 10.4244/EIJ-D-26-00889) reports the 522 patients who met ARC-HBR criteria, 17.0% of the 3,064 with HBR data.

269 were allocated to SEB and 253 to DES. 17.1% of SEB patients received a bailout stent.

The subgroup was prespecified.

The trial is open-label.

At 1 year, target vessel failure occurred in 13 of 269 (4.9%) with SEB and 20 of 253 (7.9%) with DES.

Risk difference −3.05 percentage points (95% CI −7.27 to 1.17).

BARC 3–5 bleeding: 6 vs 8 (2.3% vs 3.2%), difference −0.91 (−3.71 to 1.89). NACE: 18 vs 27 (6.8% vs 10.7%), difference −3.94 (−8.80 to 0.92).

The Central Illustration states that the substudy ‘suggests that an SEB strategy with minimal stenting is a safe and effective alternative to systematic DES implantation.’

Let’s use the parent trial as our reference.

TVF was 88 of 1,661 (5.3%) with SEB and 73 of 1,662 (4.4%) with DES, difference 0.91 (−0.55 to 2.38), non-inferior against a 2.44-point margin (one-sided p is equal 0.02).

In the per-protocol population the difference was 1.09 (−0.45 to 2.63) and non-inferiority was not confirmed. As a non-inferiority trial, ITT and PP should agree. As they don’t, we’ll stick to PP and say it wasn’t non-inferior.

Cardiac death 0.7% vs 1.0%, target vessel MI 2.7% vs 2.6%, clinically driven TVR 3.3% vs 2.1% (difference 1.22, 0.11 to 2.33).

Repeat revascularisation was in favour of the DES. Among non-HBR patients, TVF was 5.7% vs 4.0%, difference +1.79 (0.12 to 3.47).

Now, in the substudy, the HBR interval runs from −7.27 to +1.17, which contains +0.91 (the parent trial estimate). The HBR result is compatible with the parent result.

However, it has too few events to test it. RR 0.61 (0.31 to 1.20) contains a 69% relative reduction and a 20% relative increase, both compatible with 13 versus 20 events.

With 33 events, the smallest effect detectable at 80% power is a HR ~ 0.38. Bleeding: RR 0.71 (0.25 to 2.00); a 75% reduction and a doubling fit 6 versus 8 events equally well. NACE: RR 0.63 (0.35 to 1.11).

None of the three intervals excludes harm, but none excludes a large benefit.

One would think that there would be a distinct effect in HBR, but on the interaction test we got a p is equal 0.49 for bleeding. Conversely, we got p is equal 0.04 for TVF. Why would HBR have better outcomes for TVF?

Maybe because cutting antithrombotic medication would translate into higher lesion thrombosis or spontaneous MI, but both lesion thrombosis (1 vs 2; definite 1 vs 1) and TV-MI (8 vs 11) were comparable.

The HBR TVF difference is built from cardiac death 4 vs 6, target vessel MI 8 vs 11 and clinically driven TVR 4 vs 9.

All-cause death was 14 vs 13 (5.3% vs 5.2%). The protocol classifies unwitnessed and unknown-cause deaths as cardiac.

Stroke was 5 vs 1 (1.9% vs 0.4%) but it wasn’t included in the primary outcomes.

Bleeding, the only endpoint with a plausible HBR-specific mechanism, shows nothing (6 vs 8), and it behaves opposite to the logical mechanism (1 vs 7 in the first 30 days under identical regimens, 5 vs 1 afterwards).

Now, there’s something else I would like to address and it’s about the writing.

I’m no Shakespeare, but the Methods state that the intervals ‘should not be used to infer definitive treatment effects.’

The Impact box states that the data support ‘its use as an alternative revascularisation strategy in HBR patients.’

Both sentences are in the same paper, which seems contradictory to me.

To wrap this up, what I think the substudy establishes: an SEB-first strategy in 522 HBR patients had 1-year TVF of 4.9% (95% CI 2.8 to 8.1%) and lesion thrombosis 0.4%.

The patients were 68% anticoagulated and selected by operators for an anticipated bailout probability below 30%.

What it doesn’t: whether the strategy is non-inferior or superior to DES in HBR.

No hypothesis was tested, and 33 events are too few to test one.

Detecting 7.9% against 4.9% at 80% power takes about 1,040 patients per arm, four times this subset. Nonetheless, it is an important piece in building our knowledge regarding DCB PCI.

Congratulations to the authors!“

Shirley D’Sa, Professor of Haematology at UCL Cancer Institute, Advisory Council Member at Harvard Business Review:

“Cold agglutinin-associated hemolysis does not always fit neatly into our diagnostic boxes.

This new study by colleagues in Japan examines rituximab-based chemoimmunotherapy in patients with primary cold agglutinin disease and Waldenström macroglobulinemia-associated cold agglutinin syndrome.

Despite their differing underlying classifications, hematological responses were seen in both groups—100 percent in primary CAD and 80 percent in WM-associated disease – with no apparent difference in time to next treatment.

The study is small, retrospective and hypothesis-generating, but it raises a clinically relevant question:

When hemolysis is the dominant problem and precise classification remains difficult—particularly in MYD88-negative cases—might fixed-duration, clone-directed chemoimmunotherapy remain a pragmatic treatment option?

Modern diagnostic precision matters, but treatment must also address the biology causing harm to the patient.

An interesting contribution to an area in which larger, collaborative studies are much needed.

Read the open-access article: The impact of chemoimmunotherapy on primary cold agglutinin disease and Waldenström macroglobulinemia-associated cold agglutinin syndrome.“

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