PEs, POOs, plasminogen and peripheral practicalities

April 14, 2026

Casey Parker | BroomeDocs | April 2026

The modern management of proper pulmonary embolism (not the common little ones) has been evolving rapidly in the last decade. The range of acronym-based trials can seem a little dizzying. We now have PERT teams with a quiver of expensive catheters to shoot into our patients pulmonary vessels. However, we need to know what the data tells us. Not about catheters, but about our patients.

We’ve had four major PE trials drop in the last six months. Two of them were published in the New England Journal and Circulation, presented at ACC and TCT to standing rooms of interventionalists with catheters in their pockets. The internet lit up. Guidelines will be rewritten. Hospitals will buy expensive devices.

And if you work in a regional or rural hospital — which is most of the planet — almost none of it changes what you do on a Tuesday night when a sick patient rolls through your door.

Here’s what the evidence actually says, and here’s what to do with it.

A Quick Reckoning with the Evidence Base

Before we talk strategies, let’s be honest about the trials. The vast majority of recent PE intervention trials share two features that should make us cautious:

1. Surrogate endpoints. The RV/LV ratio on CT is not a patient outcome. It is a number on a scan. It has never been validated as a surrogate for death, function, or quality of life. Trial after trial has shown you can improve this number dramatically while patients go on to live identical lives — or die from your intervention’s bleeding complications.

2. Industry funding. HI-PEITHO (Boston Scientific), PEERLESS (Inari Medical), FLAME (Inari), FLASH registry (Inari), STORM-PE (device manufacturer). Every major trial producing a “positive” result in the catheter and device space was designed, run, and in many cases analysed by the companies selling the product being tested. The independently-funded trials — PEITHO, STRATIFY — consistently produce more sobering findings.

This doesn’t mean the data are fabricated. It means we should read them the way we’d read a pharmaceutical company’s drug trial: carefully, with both eyes on the patient-oriented outcomes and a hand ready to cover the surrogate endpoints.

With that said — here’s where we actually are.

First, a Note on Terminology

If you’ve been following along, you’ll know I wrote a separate post covering the new 2026 AHA/ACC PE Classification System when it dropped in February. The short version: the old “low risk / submassive / massive” language is being retired in favour of a five-category A–E system that incorporates clinical severity scores, biomarkers, RV imaging, haemodynamic parameters, and a respiratory modifier. It’s a more granular and physiologically honest framework, and it’s worth familiarising yourself with if you haven’t already.

For this post I’ll use the new categories where relevant, but I’ll keep the old terms alongside them — because most of us still think in “massive and submassive” and the trial literature uses that language throughout. The rough mapping is: New AHA/ACC Category Old terminology What it means clinically A Low risk Asymptomatic, low severity score — can go home B Low risk Symptomatic, low severity score — early discharge reasonable C1–C3 Submassive / intermediate Elevated severity score ± biomarkers ± RV dysfunction, haemodynamically stable D1–D2 Submassive trending to high Incipient cardiopulmonary failure, haemodynamics still compensating but precarious E Massive / high risk Cardiopulmonary failure, persistent hypotension, shock, arrest

Add the “R” modifier (e.g., C3R, D2R) when there’s significant respiratory compromise on top of haemodynamic findings. It’s genuinely useful shorthand when you’re on the phone to retrieval at midnight trying to convey exactly how sick your patient is and where on the spectrum they sit.

The key clinical insight from the new system: the old “submassive” bucket was always too wide. A C1 patient with mildly elevated PESI and no biomarkers is a fundamentally different clinical problem to a D2 patient with RV dilation, elevated troponin, and a lactate trending up. The new categories force more precision — and that precision matters when you’re deciding whether to give thrombolytics, call for retrieval, or watch and wait.

What Fifteen Trials Tell Us (The Short Version)

Heparin alone is not as bad as you think

The long-term follow-up of PEITHO — the largest and most rigorous dataset in this field — followed over 700 submassive PE patients for nearly three years. At that point, the patients who received heparin alone were alive in the same proportions, breathing equally well, walking equally far, and had equivalent right heart function compared to those who got full-dose thrombolysis. Identical rates of chronic thromboembolic pulmonary hypertension too.

Let that sink in. The heparin patients caught up completely.

Thrombolysis for submassive PE: real benefit is narrow, real harm is common

Full-dose systemic thrombolysis in submassive PE reduces haemodynamic deterioration events. It does not reduce mortality. It causes a 10-fold increase in intracranial haemorrhage (2% vs 0.2%). And the long-term outcomes are identical.

The only people who unambiguously benefit from systemic tPA are those whose PE is killing them right now — the haemodynamically unstable, the peri-arrest, the ones going down in front of you.

The catheter does nothing the drug can’t do through a drip

STRATIFY (2026) is the trial that should have changed everything but probably won’t, because it wasn’t funded by anyone trying to sell a catheter. It randomised intermediate-risk PE patients to three arms: heparin alone, 20mg alteplase via the EKOS pulmonary artery catheter, or 20mg alteplase through a peripheral IV over 6 hours.

The catheter and the drip were identical on every outcome including the disease-oriented thrombus burden score. Identical efficacy. Identical bleeding rates. The only difference was that the catheter costs around $5,000 more per patient and requires an operator and a procedure suite.

And the heparin arm? Zero deaths at 3 months. Both thrombolysis arms: 4.3% mortality, with the majority of deaths being bleeding-related (GI bleeds and intracranial haemorrhages).

The new devices are impressive, but the evidence is thin

PEERLESS showed that large-bore mechanical thrombectomy (FlowTriever) is roughly equivalent to catheter-directed thrombolysis in intermediate-risk PE — less ICU time, similar mortality, similar bleeding. HI-PEITHO showed that USAT catheter thrombolysis reduces haemodynamic deterioration compared to heparin alone, with a number-needed-to-treat of 16 and no mortality benefit.

Both trials are industry-funded, open-label, and use composite endpoints that dissolve when you look at the hard outcomes alone. Neither has demonstrated that the intervention saves lives or improves long-term function compared to anticoagulation.

PEERLESS II — comparing thrombectomy to heparin alone — is the trial we actually need. It’s enrolling now.

What This Means If You Work Where the Buck Stops

Here’s the thing: the entire catheter-directed thrombolysis vs mechanical thrombectomy debate is essentially irrelevant to most of the hospitals in Australia, and most hospitals on the planet. There is no FlowTriever at Fitzroy Crossing Hospital. There is no interventional radiologist in Cloncurry at midnight. In most of regional and rural Australia, the choice isn’t which device — it’s what drug, at what dose, and when.

That’s actually a liberating framing. Because the evidence supports a perfectly rational approach that requires nothing more than heparin and alteplase, both of which you almost certainly have in your pharmacy cupboard right now!

The Framework: Three Patients, Three Paths

Patient 1: Category E — Massive PE (haemodynamically unstable)

AHA/ACC Category E: Hypotension, shock, cardiac arrest, or obvious haemodynamic deterioration from PE

This is not an ambiguous situation. Act.

The mortality of untreated massive PE is horrifying — upwards of 30–50%. The mortality benefit of thrombolysis in this group is biologically plausible and supported by observational data, even without an RCT (none will ever exist for obvious ethical reasons). The calculus here is simple: untreated, they will likely die; thrombolysed, some will survive and some will bleed. Bleeding is recoverable from. Death is not.

Give systemic alteplase. Standard dosing: 100mg IV over 2 hours. If in cardiac arrest or imminent arrest: 50mg IV bolus. Stop heparin during the infusion; restart without a loading dose 2–3 hours after the alteplase completes.

If thrombolysis is absolutely contraindicated (recent neurosurgery, active intracranial pathology, recent major haemorrhage) — this is a retrieval call. Get help. Get the patient moving.

Key point: Don’t let the absence of CT confirmation delay treatment in a dying patient with a convincing clinical picture. Bedside echo showing RV dilation and McConnell’s sign, plus the clinical context, is enough to act on.

Patient 2: Categories C3 and D — Submassive PE (haemodynamically stable, but worried)

AHA/ACC Categories C3/D1–D2: Normal BP. RV strain on imaging or echo. Elevated troponin or BNP. Perhaps mildly tachycardic, mildly hypoxic, but not crashing. The D categories in particular represent patients on the edge of compensation — incipient cardiopulmonary failure.

This is where most of the controversy lives — and where the evidence most clearly supports a conservative default.

The question isn’t “should I thrombolyse?” The question is: “Is this patient genuinely trending towards haemodynamic collapse, or are they stable with risk markers that happen to look scary?”

The PEITHO data show that in unselected intermediate-risk patients, thrombolysis doesn’t save lives and produces identical long-term function — but does cause intracranial haemorrhages. STRATIFY shows that even low-dose thrombolysis in this group may produce more deaths than heparin alone, and no functional gain.

Default strategy: Anticoagulate well. Heparin infusion. Observe closely. Set a clear trigger threshold.

Triggers for escalation to systemic thrombolysis:

Sustained hypotension (SBP 15 minutes, not explained by another cause)
Clinical deterioration — increasing oxygen requirements, worsening tachycardia, altered mental state, rising lactate
Bedside echo showing worsening RV function or new right heart dilatation
You are genuinely worried this patient is going down

Do not thrombolyse purely because the CT showed a large clot burden, or the troponin is elevated, or the RV/LV ratio is >1.0. These are risk stratification markers, not treatment indications in themselves. The control arms of multiple trials demonstrate that most patients satisfying these criteria do fine with heparin.

If you decide to give low-dose thrombolysis: 50mg alteplase IV over 2 hours (consider as low as 0.5mg/kg in smaller patients or those at higher bleeding risk). This is not validated against full-dose in powered RCTs but is widely used and produces lower bleeding rates. Stop heparin during infusion.

If there is a contraindication to thrombolysis and the patient is deteriorating: This is your retrieval call. The conversation with the receiving centre now involves whether mechanical thrombectomy is available and appropriate. Give that history clearly: haemodynamic status, echo findings, reason for contraindication, current anticoagulation.

Patient 3: Categories B–C2 — Submassive PE (stable, incidental RV strain, doing OK)

AHA/ACC Categories B, C1, C2: Normal BP, saturating well, mildly tachycardic, troponin mildly elevated, RV/LV >1 on CT, but sitting comfortably asking for a cup of tea.

Anticoagulate. Watch. Resist the urge to do more.

The evidence is remarkably consistent here: these patients have excellent outcomes with heparin alone. The long-term PEITHO data, STRATIFY, and STORM-PE all tell the same story — zero to near-zero mortality in haemodynamically stable intermediate-risk patients managed with anticoagulation. You are not withholding life-saving treatment. You are applying the most evidence-supported therapy available.

Consider admission, telemetry monitoring, and a low threshold for reassessment. If they deteriorate, you escalate. That’s the evidence-based approach.

The Rural Dilemma: Give tPA Now vs. Wait 12 Hours for a Catheter?

This is the question that doesn’t appear in any of the trial papers, because none of them were run in hospitals where the nearest interventional suite is a RFDS flight away. But it’s the question that actually matters if you work in regional and remote medicine.

The scenario: you have a submassive PE patient who is borderline — not crashing yet, but worrying you. You’re considering whether to give peripheral alteplase now, or transfer them to a tertiary centre for catheter-directed therapy. The retrieval will take 12 hours minimum. What do you do?

STRATIFY has effectively answered this question, even though it wasn’t designed to. It showed that 20mg alteplase delivered peripherally through an IV produces identical outcomes to the same dose delivered through a $5,000 pulmonary artery catheter by an interventional specialist. If the drug is the treatment — and the evidence strongly suggests it is — then the catheter is just an expensive delivery mechanism for something you can give through a cannula right now.

So reframe the decision. It’s not “peripheral tPA now vs catheter-directed tPA later.” It’s really two separate questions:

Question 1: Does this patient need thrombolysis at all?

Question 2: If yes, why would I wait 12 hours to give it?

The Decision Framework

Work through it like this:

If the patient is haemodynamically unstable or deteriorating rapidly:

Don’t retrieve. Treat. Give alteplase peripherally now. Notify retrieval so they’re aware and can assist with post-lysis management or escalation if it fails — but the treatment decision is made here, because the treatment window is now. A patient in haemodynamic collapse cannot wait twelve hours for a catheter. And when they arrive at the tertiary centre twelve hours later having received peripheral alteplase, the interventional cardiologist will not be disappointed — because that’s what they would have done too, just through a longer tube.

If the patient is stable but deteriorating slowly — tachycardia climbing, O2 requirements creeping up, echo getting worse:

This is the hardest call. Two reasonable paths:

Option A — Treat and transfer: Give peripheral alteplase now (50mg over 2 hours, or consider 0.5mg/kg if smaller or higher bleeding risk). Notify retrieval. Transfer once stable post-lysis. The patient arrives at the tertiary centre having already received the most effective reperfusion available. The interventional team can reassess and manage residual clot burden or any complications.

Option B — Expedite transfer, treat en route or on arrival: Anticoagulate fully, arrange urgent retrieval, have alteplase drawn up and ready. Treat if they deteriorate during transfer or in the first few hours of transit. This is reasonable only if the trajectory is slow and transfer is genuinely fast — within 3–4 hours. For a 12-hour transfer window, this option is clinically risky.

The key point: if you think this patient is going to need thrombolysis at any point in the next 12 hours, give it now. Peripheral alteplase is not a lesser treatment you offer because you can’t do the real thing. It is the real thing.

If the patient is stable and improving on heparin:

Then they don’t need thrombolysis — peripherally or via catheter. Transfer for monitoring and definitive care is appropriate, but this is not a thrombolysis decision at all. The catheter lab at the tertiary centre is irrelevant.

If thrombolysis is contraindicated:

This is the one genuine indication for urgent transfer to access catheter-based or mechanical therapy. Recent neurosurgery, active intracranial pathology, significant recent haemorrhage — these patients cannot receive peripheral tPA, and if they deteriorate, the only option is mechanical clot removal. Flag this early. Transfer early. Don’t wait until they’re crashing.

The Conversation with the Receiving Team

When you call retrieval or the receiving unit, the new category system earns its keep here — it’s a much more precise handover tool than “submassive.” Use it:

“I have a Category D2R PE — RV/LV ratio 1.1 on CT, echo shows big RV with TAPSE of 10mm, troponin positive, on 6L O2, haemodynamically stable but trending. Thrombolysis is [indicated / not yet indicated / contraindicated because _]. Transfer time is approximately 12 hours. My question is: if this patient needs thrombolysis in the next 12 hours, should I give it peripherally now, or is there a specific reason to wait for catheter-based delivery?”

In almost every case, the honest answer from a well-read tertiary clinician will be: give it peripherally now if they need it. STRATIFY tells you the catheter adds nothing. HI-PEITHO’s benefit was in early treatment — the intervention was delivered within 2 hours of randomisation. A 12-hour delay to catheter delivery almost certainly forfeits whatever advantage catheter timing might theoretically offer.

The One Exception Worth Knowing

PEERLESS showed that large-bore mechanical thrombectomy reduces clinical deterioration compared to CDT, and produces faster early haemodynamic recovery. For the rare patient with massive PE where thrombolysis has failed — ongoing haemodynamic instability 60–90 minutes after alteplase — mechanical thrombectomy is a genuine escalation option that peripheral drugs cannot replicate. This is the patient worth urgent transfer for, and worth a direct conversation with interventional cardiology at the receiving centre while you’re still managing them.

But note: this is the post-lysis failure scenario, not the pre-treatment decision. And it applies to massive PE, not to the stable submassive patient for whom the evidence base consistently shows anticoagulation alone is adequate.

The Bottom Line on the Rural Dilemma

The catheter is not a reason to delay treatment in a deteriorating patient. If the patient needs thrombolysis, peripheral alteplase is the right treatment — not a compromise while you wait for the real thing to become available 700km away. Give it, transfer the patient, and let the receiving team manage what comes next.

The only patients who genuinely need urgent transfer before treatment are those where thrombolysis is contraindicated and mechanical options are the only path. Everyone else either needs treatment now (give it) or doesn’t need more than heparin (transfer routinely and safely).

Practical Anticoagulation Notes

Unfractionated heparin (UFH): Preferred in patients where you might need to reverse anticoagulation rapidly (potential thrombolysis candidate, haemodynamically borderline). Target aPTT 60–100 seconds.

LMWH or DOAC: Perfectly acceptable in stable patients where you are confident thrombolysis is off the table. Rivaroxaban or apixaban have the convenience advantage in hospitals with limited nursing resources.

During and after thrombolysis: Hold heparin during alteplase. Restart heparin (no loading bolus) 2–3 hours after alteplase completion once aPTT <80. Do not combine therapeutic LMWH with alteplase — PEITHO’s catastrophic ICH rate was partly driven by simultaneous full-dose tenecteplase plus full-dose heparin bolus.

The Catheter Question for Rural Clinicians: What to Tell Your Retrieval Service

You don’t have a catheter lab. That’s fine — the evidence says you don’t need one for the majority of PE patients.

What you do need to know is how to communicate the rare patient who might benefit from escalation:

Refer for consideration of catheter-directed therapy or mechanical thrombectomy when:

Massive PE where systemic thrombolysis has failed or is absolutely contraindicated
Submassive PE with clinical deterioration despite optimal anticoagulation, where thrombolysis is contraindicated (recent surgery, active intracranial pathology, recent stroke)
Large clot burden, significant haemodynamic compromise, and the patient is heading in the wrong direction.

Don’t refer for catheter-directed therapy because: The CT showed a big clot. The troponin is elevated. The RV/LV ratio is >1.0. The patient is stable and improving on heparin. These are not indications for invasive intervention.

The Bottom Line (Written for the 2am Brain)

The fancy catheter trials are interesting. The device company registries are beautifully produced. The win ratios and composite endpoints are statistically elegant.

But when you strip them back to what matters — does this patient live, does this patient bleed, can this patient walk up the stairs in six months — the evidence keeps saying the same thing: heparin is remarkably effective, thrombolysis saves lives in the truly unstable, and everything else is yet to prove its worth.

For most submassive PE patients in most hospitals, the evidence-based management plan is:

Anticoagulate promptly and well
Watch closely
Have a clear escalation trigger
Know how to give alteplase safely when that trigger is met
Know who to call when it’s not enough

That’s it. No catheter required.

Broome Docs

PEs, POOs, plasminogen and peripheral practicalities

A Quick Reckoning with the Evidence Base

First, a Note on Terminology