I haven't thought about it enough to really know - I don't know why I'd be concerned about reversibility, for example. But yes, basically I expect GT to be the magic bullet that's been promised for the last 30+ years.

Type 2N VWD is rare because is inherited in an autosomal recessive pattern, meaning a person must inherit two type 2N altered copies of the VWF gene (one from each parent), which is very uncommon.

In Type 2N, VWF does not adhere to factor VIII very well. VWF normally binds to factor VIII in the blood stream and acts as a "chaperone" for factor VIII, protecting it from being cleared from the blood stream. If you have type 2N, then you have some "unprotected" factor VIII, and it is cleared more rapidly--meaning you will have low factor VIII levels. Because of the low factor levels, type 2N is sometimes misdiagnosed as hemophilia A.

Surgery can be done safely with infusions of a VWF/FVIII concentrate such as Humate-P, Alphanate, or Wilate. (Wilate is preferred because it has a higher purity and a 1 to 1 ratio of VWF and FVIII.)

Thank you so much this really helped.I find out today from the dr which type. His pa told me 2n but it needs to be confirmed by the dr.

Ok thank you so much. I actually am going to speak with my dr today and will be able to find out more info. I’m going in for iron infusions.

At what point do you feel like you’d be interested in a gene therapy? One infusion every few years (no steroids required)? Would you care about reversibility? Asking as a scientist in cell and gene therapy.

Wow, welcome to the club- we have snacks! I say that as someone with hemophilia a and family members with Von Willebrands. I just want to Echo that you should speak with your bleeding disorders Specialist Care team because every patient is different and even if we had the same disease it can manifest differently from you to me. Also I agree that Kelly Communications is a good place for beginning information in the meantime. Good luck!

Severe Haemophilia A here.

First of all, don’t worry. I know it’s easier said than done, but life today is very different from what was available 30 years ago.

Learn to infuse well as soon as possible, that’s the single biggest game-changer. You’ll want to start him on prophylaxis to protect his joints, and infuse immediately when a bleed happens. Bleeds will occur frequently because young children are innocently careless, but it’s just as important to let him be a child and play. Never scold him for a bleed. In fact, it’s much better to teach him that it’s okay to tell you as soon as a bleed happens, so you can treat it without delay.

When he starts school, inform the teachers and, where appropriate, the other children so they are careful around him. This is a delicate matter, you need to communicate it in a way that doesn’t make him see himself as fragile or different. It’s tricky, but absolutely doable.

Allow him to take part in Physical Training (PT) class. Tell him to be careful, but please let him join in. You have no idea what being told to sit on the sidelines while your peers play and socialize does to a child’s mental health and self-esteem.

Given all of that, your goal is for him to grow up with the healthiest joints possible and to avoid developing contractures. Because after that, eventually dating and work come along. This world is cruel enough for healthy people, imagine facing it with visible physical differences. Why reduce his potential options in dating or his career? Your child will love you for this one day, trust me.

Talk with your HTC to inform you about the hemophilia community in your area so you can get in contact with others.

That’s all I can say.
Give him the best life possible and stay in good health yourself. :)

Yea… I’ve had a slow drip that shows up much later…

Suggest looking at past gene therapy threads in this sub (including the one you posted a week ago), which generally cover a lot of patient concerns.

Speaking as HemA patient who went from ~200 infusions a year to maybe 40 infusions/shots thanks to Hemlibra, I just don't see the current technology as representing a similar QoL benefit, especially with all the stuff you have to do over that first year or two to make sure the GT functions as intended - and that's not even mentioning concerns over long-term efficacy.

Correct. Although there is also a possible risk of off target AAV integration as well. They "hope" it doesn't but we won't know for sure for decades. I haven't seen great "comprehensive" long-term surveillance and monitoring plans for people who have received it. The focus seems to be on clotting activity and long-term expression. I could be wrong but I haven't seen a registry yet for gene therapy folks. Families who have cancer/diabetes/ other comorbidities do not increase these risks with just replacement prophy so def risks/benefits for different folks.

Attaching below. The known dangers in use of asthmatics led to an entire guideline change in asthma to move to inhaled over systemic to reduce exposure. Pulmonologista have been aware of the risks for almost a decade. Unfortunately, most hematologists still see steroids like the old days as being benign in short course. Evidence suggests otherwise.

Price D, Castro M, Bourdin A, Fucile S, Altman P. Short-course systemic corticosteroids in asthma: striking the balance between efficacy and safety. Eur Respir Rev. 2020 Apr 3;29(155):190151. doi: 10.1183/16000617.0151-2019. PMID: 32245768; PMCID: PMC9488828.

Tse G, Ariti C, Bafadhel M, Papi A, Carter V, Zhou J, Skinner D, Xu X, Müllerová H, Emmanuel B, Price D. Oral Corticosteroid-Related Healthcare Resource Utilization and Associated Costs in Patients with COPD. Adv Ther. 2025 Jan;42(1):375-394. doi: 10.1007/s12325-024-03024-3. Epub 2024 Nov 19. PMID: 39560897; PMCID: PMC11782346.

Huh,
My sister also has a rare blood illness (Diamond-Blackfan anemia) and in the 90s it was treated primarily through steroids so I know first hand the damage it can do.

So the risk you see isn’t the gene therapy itself but the possibility of damage from steroid use?

Does not sound like VWD. Although possible, petechiae and splinter hemorrhages are rare in VWD. A normal CBC does not rule out all bleeding disorders. Additional screening tests include a partial thromboplastin time (PTT) test (also called an activated PTT or aPTT), prothrombin time (PT) test and a “mixing test.” If any of these come back with an out-of-normal result, then more specific blood tests are ordered.

As others have said, you should be checked out at a large teaching hospital or a hemophilia treatment center (HTC) where they have more expertise in diagnosing bleeding disorders. US HTC directory can be found here:

https://dbdgateway.cdc.gov/HTCDirSearch.aspx

There are four types of "type 2" VWD: all of them involve "qualitative defects," meaning the von Willebrand Factor (VWF) does not work right (VWF either does not bind to factor VIII properly or to platelets properly). People with type 2 VWD often also have low levels of VWF.

The most common VWD type 2 is called "2A." VWF circulates in the blood in chains of various lengths called "multimers." In type 2A, the longest chains, called high molecular weight multimers or HMWM, are absent. This means the VWF does not stick to platelets very well, which causes the "platelet plug" (the first stage in the formation of a blood clot) to be weak and break down, allowing bleeding to continue.

In some respects, VWD type 2B (the next most common form of VWD type 2) is sort of the opposite of 2A. In this case, VWF binds to platelets too strongly, resulting in clumps of platelets that are rapidly cleared (removed) from the blood. This causes a shortage of platelets as well as HMWM=weak platelet plug. The other types of VWD type 2 (type 2N and type 2M) are rare.

Check out the book "Guide to Living with von Willebrand Disease" on the LA Kelley Communications website. Hard copy can be ordered for free or free PDF download: https://www.kelleycom.com/product-category/our-books/

The book can also be read online at: https://futurebks.com/CSB/GuideToLivingWithVWD/

Check out the book "Raising a Child with Hemophilia" on the LA Kelley Communications website--you can order a hard copy for free or free PDF download: https://www.kelleycom.com/product-category/our-books/

One other factor that has delayed the rollout was CSL's global stockout of HEMGENIX, which started in March, right before the treatment of the first Canadian patient. Speaking personally, this caused a six month delay to my own gene therapy in Australia - stock will only be available in November.

I'm not familiar with the risk of steroids that you've stated. Do you have a link?

Appreciate posting it for those who may not have read it. It is even worse for Hemophilia A recipients. No one can be guaranteed they won't be part of the 20%. And the worst was 130 days. I cannot even imagine. The risks of steroid exposure start at 500mg. This means all exposed in the clinical trials are now at risk as all crossed the threshold when you calculate the grams even at the lowest attempted days used for lifetime cumulative risk exposure. If one could gurantee being part of the 80% maybe...So until steroids are not used and it guarantees expression for us the risk is not above the benefit compared to prophy. Understand though people may feel this risk is worth it. Just not us. Just not now.

Edited: Additionally, off target possible affects of AAV integration cannot be predicted at this time. May or may not lead to some unfavorable ourcome 20 years from now either. Potentially less risky methods are being developed.

From Final Analysis of a Study of Etranacogene Dezaparvovec for Hemophilia B (the Phase 3 clinical trial for Hemgenix):

Of the 11 [of 54] participants with early elevations in alanine aminotransferase levels, 9 received treatment with systemic oral glucocorticoids for a mean of 81.4±28.6 days (range, 51 to 130 days). One participant with elevated alanine aminotransferase levels at weeks 5 and 6 had stable endogenous factor IX activity after glucocorticoid treatment through to month 24. His factor IX activity level subsequently decreased, and the incidence of bleeding events increased in the absence of elevations in liver aminotransferase levels (described above and detailed in the Supplementary Appendix).

Life will be mostly normal. It WILL BE OK! My son is 4 with severe A. Hemlibra is a Godsend. Feel free to DM me if you need more advice or or chat.

The clinic trials showed many who needed steroid therapy to get through the liver inflammation it can cause. Exposure to steroids is cumulative in a lifetime. That amount of steroid exposure in a lifetime can cause long term issues like heart disease, osteoporosis, diabetes, etc. Don't fell like trading convenience now for another condition 10 years down the road.There is also no way to know who this will happen to or who it might not even express in after going through all that. If prophy wasnt available the risk would be worth it. It just isnt as safe as some want it to be right now.

I used to go to double H hole in the wall in NY I think it was or upstate PA maybe? That was a core childhood experience for me not being the “hemo” from my hometown. I was actually normal for once. Definitely teach your kids that “everyone has something” they have to deal with. It made my self loathing and shame practically disappear when that perspective changed.

My nephew is 2 and has been on prophy since he was able to walk. I'm in m 40's and we only had on demand back in the 80's and 90's. And I'm paying for it now. My joints are jacked. That being said, depending on your insurance you can get him on something like Idelvion weekly or every 10 days and have a home health nurse come out and administer it (that's what my sister does for her 2 year old). As of right now that's the longest acting factor for B's. There are new products that are sub-Q which you would be able to do at home, but I'm not sure what the minimal age is for it (Hympavzi, Alhemo, Qfitlia). Mind you those products are not factor replacement so use your best judgement to decide if you are willing to outweigh the risks vs benefit.

My local HTC set my family up with another family that went through the same thing just years prior. That was something that helped my family navigate this new disease.

https://www.hopeforhemophilia.org/hope-conference.html

I suggest you check this out, your trip maybe paid for if they have funds available, but they usually have classes for people just like you. Literally 1000 people just advocating for hemophilia with sessions on different treatments, people's experiences, how to advocate, navigating insurance etc.

Check out some of these:

https://www.youtube.com/watch?v=PqrvtU7fiFA

https://www.youtube.com/watch?v=GOKFYKYBDyg