SPEAKER_00 0:00

Imagine bleeding for days after um just a simple tooth extraction, yet every single blood test your doctor runs comes back perfectly normal.

SPEAKER_02 0:09

Yeah, which is a terrifying situation for a patient.

SPEAKER_00 0:12

Right. I mean the medical lab says you're fine, but your body's basically screaming that you are in danger. You know, usually when we talk about a medical diagnosis, there's this expectation of like precision.

SPEAKER_02 0:24

Right, like engineering.

SPEAKER_00 0:25

Exactly, like engineering. Yeah. You break your arm, the x-ray shows that jagged white line, and the doctor just points and says, There it is, broken or not broken.

SPEAKER_02 0:33

We really crave that binary, don't we? We want our biology to be visible and, you know, neatly categorized.

SPEAKER_00 0:39

We're right onto a spreadsheet. But then you step into the world of hemostasis and bleeding disorders, and suddenly that x-ray machine is, well, it's completely broken.

SPEAKER_02 0:47

Aaron Powell It's a very murky diagnostic landscape.

SPEAKER_00 0:50

It really is. And today's deep dive is based on a really extensive clinical overview by William Ayrt, all about the clinical manifestations of von Wilbrand disease, or VWD.

SPEAKER_02 1:00

And this source material is fantastic because it really challenges how we view bleeding.

SPEAKER_00 1:05

Yeah, and that's actually our mission today. We want to completely shatter your preconceived notions about what a bleeding disorder actually looks like. Because it turns out it's not about someone just spontaneously bleeding all the time.

SPEAKER_01 1:15

No, not at all. It's much more complex.

SPEAKER_00 1:17

It is a detective story. It's about how the human body responds to very specific, intense moments of stress. So we're going to invite you to look at your own medical history not just as like a static list of dates and symptoms, but as a dynamic record of biological performance. Okay, let's unpack this. Where do we even begin with a condition that just seems to hide in plain sight?

SPEAKER_02 1:43

Well, we begin by changing the fundamental question we ask. In medicine, the default question is almost always does this patient bleed?

SPEAKER_00 1:50

Which seems like the obvious question, right?

SPEAKER_02 1:52

It seems obvious, but according to this overview, that is entirely the wrong question. It actually leads to a lot of misdiagnoses.

SPEAKER_01 1:58

Oh wow. Okay.

SPEAKER_02 1:59

The right question, the one that actually unlocks the biology of VWD, is when has this patient's hemostatic system been tested and what happened when it was?

SPEAKER_00 2:08

A test. Okay. So let's look at the biology of this test. The source describes VWD as a mucocutaneous bleeding disorder, which is a bit of a mouthful.

SPEAKER_01 2:19

It is a mouthful, yeah.

SPEAKER_00 2:20

But to understand what it means, we have to look at the protein at the center of all of this, which is von Willebrand factor, or VWF. And from what I gathered, this protein essentially has um two main jobs in the body. Trevor Burrus, Jr.

SPEAKER_02 2:33

Right, two very specific jobs.

SPEAKER_00 2:35

Aaron Powell First, it acts like a sticky tether, supporting platelet adhesion at the exact sites where a blood vessel is injured. But it specifically does this under high shear stress, meaning fast flowing blood.

SPEAKER_02 2:45

Yes, the mechanical flow matters a lot.

SPEAKER_00 2:47

Aaron Powell And then the second job is that it acts as a carrier and a stabilizer for another crucial clotting protein called factor eighth.

SPEAKER_02 2:54

Aaron Powell And the mechanics of that first job, you know, the tethering under shear stress is really where the paradigm shift happens. Von Willebrand factor doesn't just float around in your blood as an active sticky net.

SPEAKER_00 3:05

Because if it did, what you'd just be clotting constantly.

SPEAKER_02 3:08

Exactly. You'd be forming microscopic clots everywhere all the time, which would be fatal. So instead, it travels in this tightly coiled shape, almost like a balled-up piece of yarn.

SPEAKER_00 3:19

Oh, interesting. So it's inactive while it's traveling.

SPEAKER_02 3:21

Right. It only uncoils and becomes sticky when it is subjected to high shear stress. Think of a rushing river being forced through a narrow gorge.

SPEAKER_00 3:30

Okay, I can picture that.

SPEAKER_02 3:32

When a blood vessel is injured, the flow dynamics change rapidly, and that physical mechanical pressure actually forces the VWF to unroll, exposing its sticky binding sites so the platelets can grab on.

SPEAKER_00 3:44

So it's like um VWF is a city's emergency structural reinforcement system. It's like deploying thousands of sandbags, but only when the flood waters reach a specific critical velocity.

SPEAKER_02 3:56

That's a great way to put it.

SPEAKER_00 3:57

If there's no flood, you don't need the sandbags, and you don't even know they're missing from the warehouse. But wait, let me push back on this a bit. If I don't bleed every single day, could I still realistically have a full-blown bleeding disorder? Like how does someone go years, maybe decades, without realizing their biological sandbags are completely missing?

SPEAKER_02 4:16

What's fascinating here is the distinction between having a biological vulnerability and having that vulnerability actually tested by the real world.

SPEAKER_00 4:24

Ah, right. The test we talked about.

SPEAKER_02 4:26

Exactly. A patient with VWD might look perfectly well between challenges. The disease is there. The genetic or acquired deficiency is physically present. But every day, resting life simply hasn't required that emergency reinforcement yet.

SPEAKER_00 4:40

Because the floodwaters haven't risen.

SPEAKER_02 4:42

Exactly. The absence of bleeding doesn't mean normal hemostasis. It just means a meaningful biological test hasn't occurred yet.

SPEAKER_00 4:49

Which begs the question for anyone listening. If sitting on the couch or going for a light jog doesn't test the system, what does? Yeah. And this takes us into what the overview calls the mucosal battlegrounds.

SPEAKER_02 4:59

Right. The mucocutaneous aspect.

SPEAKER_00 5:01

Yeah. We mentioned earlier it's a mucocutaneous disorder. The typical bleeding pattern involves the nose, the mouth, gums, skin, the uterus, and the gastrointestinal mucosa. Why are these specific surfaces the ones demanding those emergency sandbags?

SPEAKER_02 5:17

Because those environments are incredibly hostile to clot formation. Think about the inside of your mouth or your GI tract. They are highly vascularized, meaning they have a very dense network of blood vessels.

SPEAKER_00 5:29

Which means more chances to bleed.

SPEAKER_02 5:31

Right. But more importantly, they are constantly subjected to friction, local trauma, and microbial inflammation.

SPEAKER_00 5:38

Oh, because we're always chewing and swallowing.

SPEAKER_02 5:40

Exactly. And then you add in a process called local fibrinolysis.

SPEAKER_00 5:44

Fibrinolysis.

SPEAKER_02 5:45

Yes, which is the boder's own mechanism for breaking down blood clots. Your saliva, for instance, literally contains enzymes designed to dissolve clots so that small scrapes in your mouth don't turn into massive obstructive scabs.

SPEAKER_00 5:57

Oh wow. So you're trying to form a life-saving clot in a wet moving environment that is actively trying to dissolve the very patch you're trying to build.

SPEAKER_02 6:04

Exactly. It's fighting against you.

SPEAKER_00 6:06

That is a completely different scenario than getting a simple paper cut on your finger.

SPEAKER_02 6:11

Totally different. Add the mechanical reality to that. In the nasal passages or the GI tract, you can't easily apply pressure and immobilize the wound like you can with a cut on your arm.

SPEAKER_00 6:21

Right. You can't put a tourniquet on your stomach.

SPEAKER_02 6:23

No, you can't. The tissue is always moving. You are swallowing, speaking, digesting. VWF is exceptionally critical in these settings because it helps those initial platelets grab on and hold tight under that constant mechanical flow and stress.

SPEAKER_00 6:38

So if it's not there, they just get swept away.

SPEAKER_02 6:40

Right. When VWF is low or dysfunctional, or maybe cleared from the body too quickly, that initial platelet plug just washes away. Because of this, VWD often doesn't present as bleeding, starting in bizarre random places. It presents as ordinary bleeding that behaves abnormally.

SPEAKER_00 6:58

Aaron Ross Powell Like a nosebleed that just won't quit. Or bleeding after a dental extraction.

SPEAKER_02 7:02

Yes, dental extractions are a huge test.

SPEAKER_00 7:05

Aaron Ross Powell The dental extraction was highlighted so specifically in the sources. Pulling a tooth is basically the ultimate hemostatic stress test. You've got rich vascularity, massive tissue disruption, pooling saliva, delivering those clot busting enzymes we talked about, and mechanical stress every single time you swallow or speak.

SPEAKER_02 7:26

It's the perfect storm.

SPEAKER_00 7:27

It really is. But let me ask a practical question on behalf of the listener. Kids get bruises and nosebleeds all the time. I mean, it's a standard part of growing up. How do you know when a clumsy Tuesday is just a clumsy Tuesday and when it is actually, you know, VWF biology made visible?

SPEAKER_02 7:44

That's a great question. It comes down to crossing a threshold. Bruising and epistaxis, which are nosebleeds, are incredibly common in the general population.

SPEAKER_00 7:52

Everyone gets them.

SPEAKER_02 7:53

So the mere presence of a bruise tells us almost nothing. The clinical red flags are found in the severity and the context. Like how bad it is. Exactly. Is the bruising spontaneous? Is it wildly out of proportion to the trauma? We also look for palpable lumps under the bruises.

SPEAKER_00 8:07

Aaron Powell, hematomas, not just surface discoloration.

SPEAKER_02 8:09

Aaron Powell Right, hematomas. And with nosebleeds, the clues are in the duration, whether it's happening heavily in both nostrils, and most importantly, the need for medical intervention.

SPEAKER_00 8:19

Aaron Powell Medical intervention. Like they actually have to go to the doctor for it.

SPEAKER_02 8:22

Aaron Powell Did the child need nasal packing or cottery to finally stop the bleeding? That's the threshold.

SPEAKER_00 8:27

Aaron Powell Okay, so we aren't looking for the presence of the event. We're looking at the behavior of the event. And since these symptoms often just like blend in with normal life events, we really need to follow the chronological timeline of human life to see how these tests of hemostasis evolve over time.

SPEAKER_02 8:45

Yes, because the tests change.

SPEAKER_00 8:46

A five-year-old faces very different physical challenges than a 30-year-old.

SPEAKER_02 8:50

In childhood, as we noted, the clues are often those recurrent severe nosebleeds or extreme bruising. But another major early test is a tonsilectomy.

SPEAKER_00 9:00

Right, getting your tonsils out.

SPEAKER_02 9:01

The sources flag tonsilectomies as a notoriously high risk procedure for VWD patients. Obviously, they involve the airway, which is inherently dangerous. But the key biological insight here is the timeline of the bleeding.

SPEAKER_00 9:13

What do you mean by the timeline?

SPEAKER_02 9:15

Well, initial hemostasis right after the surgery might look completely fine.

SPEAKER_00 9:19

Because the surgeon is right there fixing it.

SPEAKER_02 9:21

Exactly. The surgeon is actively cauterizing vessels. But days later, as the throat tries to heal, as those scabs begin to shift in a wet, mobile environment, a sudden lack of VWF reserve can lead to severe delayed bleeding.

SPEAKER_00 9:36

Wow. So the structural reinforcement fails right when the healing process demands it the most.

SPEAKER_02 9:41

Yes, it's a delayed failure.

SPEAKER_00 9:42

And as we move into adulthood, the challenges shift dramatically. Pregnancy is a fascinating evolutionary test here. The sources note that VWF and factor VII actually rise significantly during pregnancy in many patients, particularly those with type 1 VWD.

SPEAKER_02 9:58

Which is an amazing biological adaptation.

SPEAKER_00 10:00

It is. Mammalian biology naturally ramps up its clotting factors in preparation for the massive vascular wound that occurs when the placenta detaches. So the disease essentially masks itself.

SPEAKER_02 10:11

Completely hides.

SPEAKER_00 10:12

The patient might look totally normal on a blood test in their third trimester. But then after delivery, those protective levels plummet rapidly, which can lead to life-threatening primary or secondary postpartum hemorrhage.

SPEAKER_01 10:24

Which is unfortunately very common and very dangerous.

SPEAKER_00 10:27

But before we even get to pregnancy, there is a massive physiological test that happens in adolescence. The case study in the overview centers on a 16-year-old girl. She presents with heavy menstrual bleeding. Her menses last eight to ten days with the passage of large clots, and she's changing her protection every one to two hours. She's literally missing school.

SPEAKER_02 10:49

For patients who menstruate, the uterus becomes the very first repeated high-demand test of primary hemostasis.

SPEAKER_00 10:56

Right, because it happens every month.

SPEAKER_02 10:57

The sheer surface area of the endometrial lining shedding every month is a massive structural challenge. The source gives us highly practical clues for when menstrual bleeding crosses from what society might deem, you know, just heavy into what a hematologist deems clinically significant.

SPEAKER_00 11:12

What are those clues?

SPEAKER_02 11:13

We're looking at blood clots larger than about one inch in diameter, and the need to change a pad or tampon more frequently than once an hour.

SPEAKER_00 11:20

Here's where it gets really interesting, though. If a 16-year-old is losing that much blood every single month, how is her body physically sustaining that? It can't just be about the visible blood loss. Like what is happening to her internal reserves?

SPEAKER_01 11:35

And that is the crucial question.

SPEAKER_00 11:36

Because here is where the diagnostic tract really springs shut. In this 16-year-old's lab results, her hemoglobin is only mildly reduced. If a rushed doctor just looks at that standard measure, they might just say, Oh, you're fine, you're not technically anemic.

SPEAKER_02 11:51

Which happens all too often.

SPEAKER_00 11:52

But her ferritin, which measures the body's actual stored iron, is sitting at eight nanograms per milliliter, which is severely depleted. We live in a society that so often writes off heavy menstruation as just a quality of life issue, or just, you know, the unfortunate reality of being a woman.

SPEAKER_01 12:09

It's completely normalized.

SPEAKER_00 12:10

Yeah, normalized. But in reality, for this teenager, her uterus is the first major hemostatic stress test her body has ever faced, and it is catastrophically failing.

SPEAKER_02 12:19

Heavy menstrual bleeding must be viewed as vital hematologic evidence of reduced hemostatic reserve. It is not just a gynecological complaint.

SPEAKER_00 12:27

Right, it's a blood disorder symptom.

SPEAKER_02 12:29

Exactly. A normal hemoglobin does absolutely nothing to exclude clinically important iron loss, particularly with chronic mucosal bleeding. The body will drain its iron stores completely dry just to maintain that baseline hemoglobin level.

SPEAKER_00 12:44

So it's basically cannibalizing its own iron to keep up appearances in the blood.

SPEAKER_02 12:48

Yes. Ferritin is the biological narrative of that struggle. If a clinician ignores a crash ferritin level just because the hemoglobin is borderline okay, they are entirely missing the story of what that young woman's body is going through to survive its own biology.

SPEAKER_00 13:04

It's a literal record of biology under stress.

SPEAKER_02 13:06

Yeah.

SPEAKER_00 13:06

But VWD doesn't just hide in common mucosal bleeding. It's also um it's sort of a shapeshifter.

SPEAKER_01 13:13

Yeah, very much so.

SPEAKER_00 13:14

The overview points out that if we look at more severe subtypes, the disease can completely disguise itself as something else entirely. For instance, mimicking hemophilia.

SPEAKER_02 13:23

Right. Most VWD bleeding is mucocutaneous, happening at the surface levels like the mouth or the uterus. But severe type 3 VWD and a specific variant called type 2N look exactly like hemophilia.

SPEAKER_00 13:37

How so?

SPEAKER_02 13:38

Instead of surface bleeding, these patients experience deep tissue bleeding, massive muscle hematomas, and bleeding directly into their joints, which is known as hemothrosis.

SPEAKER_00 13:48

Bleeding into the joints. And this goes all the way back to that second job of VWF we mentioned at the very start, acting as the carrier and bodyguard for factor eight.

SPEAKER_02 13:57

Because VWF isn't just a sticky net, it is the essential transport vehicle for factor eight. In severe VWD, if you have almost no VWF, or if you have the type 2N variant where your VWF is structurally incapable of binding to Factor VIII, your factor eight levels absolutely plummet.

SPEAKER_00 14:13

Wait, so the body is still making factor eight?

SPEAKER_02 14:15

The body might be producing factor eight perfectly well, but without its carrier protein to shield it in the bloodstream, it just gets degraded and cleared from the blood almost instantly.

SPEAKER_00 14:22

So a doctor looks at the lab, sees practically zero factor eight, and immediately assumes, ah, hemophilia. But it's a brilliant disguise. The actual problem isn't the cargo, it's the delivery truck. Now what about older adults? The source has mentioned that as patients age, the presentation shifts toward gastrointestinal bleeding and something called angiodysplasia.

SPEAKER_02 14:43

Yes, angiodisplasia.

SPEAKER_00 14:45

Which involve these fragile, swollen, dilated blood vessels in the gut that form as we age. And this ties into acquired von Willebrand syndrome. So what does this all mean for someone who suddenly starts bleeding heavily in their 70s? Did the disease just hide perfectly for seven decades?

SPEAKER_02 15:02

If we connect this to the bigger picture, we have to firmly separate inherited genetic failure from acquired biological failure. In older adults, you can develop acquired von Willebrand syndrome even if you were born with perfectly normal genetics and have no lifelong history of bleeding whatsoever.

SPEAKER_00 15:17

Wow, it just appears out of nowhere.

SPEAKER_02 15:19

It does, and this acquired version is often associated with other severe medical conditions. For example, a patient might have severe aortic stenosis, which is a tightly narrowed heart valve, or they might be living with an L V A D, which is a mechanical heart pump implanted in their chest.

SPEAKER_00 15:34

Wait, I need to pause you right there because this is where the biology feels completely disconnected to me. A mechanical heart pump is in the chest. Aortic stenosis is a heart valve issue. Angiodysplasia is happening all the way down in the gut. Are you saying the mechanical action of the heart pump is physically altering the structure of the blood before it even reaches the stomach?

SPEAKER_02 15:55

It is literally shredding it.

SPEAKER_00 15:57

Shredding it.

SPEAKER_02 15:58

It comes down to pure physics. Remember how we said VWF uncoils under sheer stress?

SPEAKER_00 16:03

Yeah, the fast-flowing river.

SPEAKER_02 16:05

Well, VWF circulates in these massive sticky nets called high molecular weight multimopers. They're huge, complex protein structures. When blood is forced through a narrowed, calcified heart valve in aortic stenosis, or when it is ground through the rapidly spinning mechanical rotors of an LVAD, the extreme sheer stress is so violent that it physically breaks those high molecular weight multimochers apart.

SPEAKER_00 16:31

Oh my god.

SPEAKER_02 16:32

The essential protein is mechanically destroyed by the cardiovascular system.

SPEAKER_00 16:35

So the sandbags aren't missing, they're just getting ripped apart by a wood chipper before they can reach the flood.

SPEAKER_02 16:40

That is exactly what is happening. And down in the gastrointestinal tract, those aging, fragile, swollen vessels, the angiodisplasia, are constantly developing microscopic leaks.

SPEAKER_00 16:49

That's naturally.

SPEAKER_02 16:50

Right. And normal platelets aren't enough to patch them. They specifically require those massive, intact, high molecular weight stickiness to seal the weird, low-pressure dilated leaks. Without them, the patient suffers severe, recurrent, often life-threatening gastrointestinal bleeding.

SPEAKER_00 17:09

That is mind-blowing. The plumbing of the heart destroys the structural integrity of the blood, which causes a leak in the stomach. The human body is just absurdly interconnected.

SPEAKER_02 17:17

It truly is.

SPEAKER_00 17:18

But this sheer complexity brings us to perhaps the most frustrating part of this entire deep dive: the diagnostic illusion. Given that this disease is completely dependent on real-world challenges, that it brilliantly mimics other disorders, that it shifts depending on age or pregnancy, and can literally be shredded by a heart valve. How on earth do doctors actually catch it? Because the standard medical testing seems completely broken here.

SPEAKER_02 17:41

The standard screening tests are indeed highly deceptive. A patient can have a completely normal platelet count. They can have a normal PT or prothrombin time, they can have a normal APTT.

SPEAKER_00 17:52

All normal.

SPEAKER_02 17:53

All the standard routine coagulation screens can come back perfectly normal, and that patient can still be suffering from a severe, life-threatening form of von Willebrand disease.

SPEAKER_00 18:02

Aaron Powell Let me just express some frustration on behalf of anyone listening who has ever felt dismissed by a doctor. It feels like these standard medical tests are practically gaslighting patients. How is it biologically possible to have a completely normal clotting time on a piece of paper in a lab, but then bleed endlessly after a dental extraction in reality?

SPEAKER_02 18:22

Aaron Powell This raises an important question about what we are actually measuring in a laboratory setting.

SPEAKER_00 18:27

Okay, what are we measuring?

SPEAKER_02 18:28

The standard PT and APT tests are conducted in a static plastic or glass test tube. They measure the chemical cascade of clotting factors and still fluid, but they completely fail to replicate the dynamic sheer stress of flowing blood.

SPEAKER_00 18:42

Because it's just sitting in a tube.

SPEAKER_02 18:44

Right. They do not replicate the stretching of endothelial cells or the local fibrinolysis happening in a saliva-filled mouth, or the mechanical friction of a healing tonsillectomy.

SPEAKER_00 18:55

But even the more advanced tools seem to fail here. The overview talks about the PFA 100, which is supposed to simulate blood flow. But it works by drawing blood through a tiny synthetic aperture coated with collagen.

SPEAKER_01 19:09

It's just a simulation.

SPEAKER_00 19:10

Right. It's still just a plastic tube. It doesn't have active saliva, it doesn't have healing tissues sloughing off, and it has been proven unreliable for firmly ruling out VWD when the patient's real world story strongly suggests they have it.

SPEAKER_02 19:24

We also see major limitations with B bats or bleeding assessment tools.

SPEAKER_00 19:28

What are those?

SPEAKER_02 19:28

These are structured questionnaires designed to score a patient's bleeding history. But a low score on a bat doesn't necessarily mean your blood clots normally. It might just mean you've had a very quiet life.

SPEAKER_00 19:39

Like we said earlier, no floods, no need for sandbags.

SPEAKER_02 19:42

Right. A low bleeding score in a young child who has never had surgery, never had a major injury, and hasn't started menstruating is practically meaningless. They haven't had enough hemostatic challenges to fail one yet. You cannot trust normal screening tests if the patient's real world lived history is screaming that there's a problem. Right. William Aired makes a definitive statement in the overview. He says, bleeding is not a laboratory value. It is the clinical result of a hemostatic system meeting real world challenges.

SPEAKER_00 20:12

Bleeding is not a laboratory value. That is the core of it. The lab is just a snapshot, but the bleeding is the actual movie. So to truly diagnose this, you can't just order the standard generic panel and call it a day. You have to order focused, specific testing interpreted strictly within the context of the patient's life, right? Like VWF antigen levels, platelet-dependent VWF activity, and factor eight activity.

SPEAKER_02 20:35

Yes, those specific tests are key.

SPEAKER_00 20:36

And even then, you have to interpret those specific numbers against the backdrop of their unique physical challenges.

SPEAKER_02 20:43

And clinicians have to be willing to repeat those specialized tests too. Because as we saw with evolutionary biology of pregnancy or, you know, with periods of acute inflammation, those protein levels fluctuate wildly.

SPEAKER_01 20:54

They move around.

SPEAKER_02 20:55

The diagnosis is never just a single data point. It is an ongoing clinical synthesis. It is the complex interaction between VWF biology, the specific vascular bed being tested, the severity of the hemostatic challenge, and time. Treating the patient sitting in front of you, listening to their actual lived experience with bleeding, with heavy menstruation, with prolonged healing is vastly more important than blindly trusting a normal result on a static screening test.

SPEAKER_00 21:21

So to synthesize our deep dive today, von Willebrand disease isn't simply about missing a protein. It's a dynamic, shifting interaction between biology, your vascular beds, and time. It's about a hemostatic reserve that looks perfectly fine when you're resting on the couch, but entirely collapses when the physical flood waters rise. I really hope this encourages you to re-evaluate how you look at your own medical history. It is not just a chronological timeline of appointments and standard lab results, it's a vital, lived record of exactly how your specific body handles stress.

SPEAKER_01 21:53

It really is.

SPEAKER_00 21:54

Which brings me to a final thought I want to leave you with, something to mull over long after this deep dive ends. If a complex genetic condition like von Willebrand disease can remain perfectly, silently hidden in a person's body for years or even decades, until a highly specific environmental trigger or mechanical heart pump or a surge in hormones finally forces it into the light, what other latent traits, incredible hidden strengths or unknown biological vulnerabilities, are lying dormant in our DNA right now, just waiting for the exact right or wrong challenge to finally reveal themselves? Turns out our biology isn't a clean X ray after all. It's an untested map, just waiting for the territory.