Hemostatic abnormalities in patients with Ehlers–Danlos syndrome, 2018, Artoni et al.

[SNT Gatchaman]

Hemostatic abnormalities in patients with Ehlers–Danlos syndrome
A. Artoni; A. Bassotti; M. Abbattista; B. Marinelli; A. Lecchi; F. Gianniello; M. Clerici; P. Bucciarelli; S. La Marca; F. Peyvandi; I. Martinelli

Background: Ehlers–Danlos syndrome (EDS) includes a heterogeneous group of connective tissue disorders affecting skin, bones, vessels, and other organs. Patients with EDS have an increased risk of bleeding, but a comprehensive study of hemostasis in EDS patients is lacking.

Objective: To investigate the bleeding tendency of a cohort of patients with EDS by using the Bleeding Assessment Tool of the ISTH, the bleeding severity score (BSS).

Methods: The BSS was defined as abnormal when it was ≥ 4 in men and ≥ 6 in women. Patients with a bleeding tendency were compared with those without in terms of type and number of hemostatic abnormalities.

Results: Fifty-nine of 141 patients with EDS (41.7%) had an abnormal BSS. Prothrombin time and activated partial thromboplastin time were slightly prolonged in 10 patients (7.1%) because of mild coagulation factor deficiencies, which were not responsible for the bleeding diathesis. von Willebrand factor antigen, ristocetin cofactor, endogenous thrombin potential and platelet count were normal in all patients. At least one platelet function abnormality was found in 53 patients (90%) with an abnormal BSS and in 64 (78%) with a normal BSS (adjusted odds ratio [OR] 2.55, 95% confidence interval [CI] 0.877.48). The risk of bleeding progressively increased with the number of platelet function abnormalities, reaching an OR of 5.19 (95% CI 1.32–20.45) when more than three abnormalities were detected.

Conclusions: Our results show that nearly half of patients with EDS have an abnormal BSS, which, in 90% of cases, appear, at least in part, to be attributable to platelet function abnormalities. Abnormalities of primary hemostasis may contribute to the risk of bleeding in patients with EDS.

Link | PDF (Journal of Thrombosis and Haemostasis)

 

[Ash]

Hemostatic abnormalities in patients with Ehlers–Danlos syndrome
A. Artoni; A. Bassotti; M. Abbattista; B. Marinelli; A. Lecchi; F. Gianniello; M. Clerici; P. Bucciarelli; S. La Marca; F. Peyvandi; I. Martinelli

Background: Ehlers–Danlos syndrome (EDS) includes a heterogeneous group of connective tissue disorders affecting skin, bones, vessels, and other organs. Patients with EDS have an increased risk of bleeding, but a comprehensive study of hemostasis in EDS patients is lacking.

Objective: To investigate the bleeding tendency of a cohort of patients with EDS by using the Bleeding Assessment Tool of the ISTH, the bleeding severity score (BSS).

Methods: The BSS was defined as abnormal when it was ≥ 4 in men and ≥ 6 in women. Patients with a bleeding tendency were compared with those without in terms of type and number of hemostatic abnormalities.

Results: Fifty-nine of 141 patients with EDS (41.7%) had an abnormal BSS. Prothrombin time and activated partial thromboplastin time were slightly prolonged in 10 patients (7.1%) because of mild coagulation factor deficiencies, which were not responsible for the bleeding diathesis. von Willebrand factor antigen, ristocetin cofactor, endogenous thrombin potential and platelet count were normal in all patients. At least one platelet function abnormality was found in 53 patients (90%) with an abnormal BSS and in 64 (78%) with a normal BSS (adjusted odds ratio [OR] 2.55, 95% confidence interval [CI] 0.877.48). The risk of bleeding progressively increased with the number of platelet function abnormalities, reaching an OR of 5.19 (95% CI 1.32–20.45) when more than three abnormalities were detected.

Conclusions: Our results show that nearly half of patients with EDS have an abnormal BSS, which, in 90% of cases, appear, at least in part, to be attributable to platelet function abnormalities. Abnormalities of primary hemostasis may contribute to the risk of bleeding in patients with EDS.

Link | PDF (Journal of Thrombosis and Haemostasis)

It’s so scary. More so because
there seems little medical willingness to look into these problems and assess for them.


Everywhere you look a disease affecting a greater proportion of female than male patients, is trivialisation and ignorance.

Even measurable factors aren’t taken seriously because of refusal to look for them or to assess them in context, ignorance of how to deal with them even if found. Resentment of patients asking for treatment for their conditions.

I’don’t know of many men making their struggles public over EDS, I remember a couple but not exactly what they said, this was a long time ago. So I think they were disbelieved and treated worse before but also struggled after EDS genetic confirmation. I don’t think this followed quite the same pattern as for women in the same position. I’d like to really know. I’m guessing it’s like for us here where getting something assigned, a ‘condition primarily affecting females’ is an absolute disaster for one’s credibility and chances of getting treated.

 

[Tilly]

It’s so scary. More so because
there seems little medical willingness to look into these problems and assess for them.


Everywhere you look a disease affecting a greater proportion of female than male patients, is trivialisation and ignorance.

Even measurable factors aren’t taken seriously because of refusal to look for them or to assess them in context, ignorance of how to deal with them even if found. Resentment of patients asking for treatment for their conditions.

I’don’t know of many men making their struggles public over EDS, I remember a couple but not exactly what they said, this was a long time ago. So I think they were disbelieved and treated worse before but also struggled after EDS genetic confirmation. I don’t think this followed quite the same pattern as for women in the same position. I’d like to really know. I’m guessing it’s like for us here where getting something assigned, a ‘condition primarily affecting females’ is an absolute disaster for one’s credibility and chances of getting treated.

From my work with those needing and EHCP with EDS this is transferable to Fabricating or Inducing Illness in a child. You ask for appropriate assessments or support you have nowhere to go as those who supported EDS are targeted and some have been taken down. The lead person you would turn to does not believe in ME, so go figure that one. Even with all the joints that would meet the criteria for EDS soft skin and easy bruising Social Workers can give their opinion that it is an FII case. Even if you give evidence of each joint being unstable, dislocated apparently a young person can over exaggerate.

So many young people with ME end up with more bendy/dislocated joints than they did before becoming ill and this is never tracked and so DATA and reality is never tracked. I think some researchers are picking up on this with the connection with POTS but it needs research how the ME impacts on connective tissue.

 

[SNT Gatchaman]

I’m guessing it’s like for us here where getting something assigned, a ‘condition primarily affecting females’ is an absolute disaster for one’s credibility and chances of getting treated.

That's one of the reasons I've tried to be very open about this with medical colleagues, and help get the message out. I would hope I have sufficient pre-existing credibility to counter the narrative. However, I think it's still potentially very easy for people to re-pigeonhole someone and simply forget or reframe their prior knowledge of them.

I would note that there is at least one condition primarily affecting females and rarely affecting males that does not suffer from this credibility problem at all: breast cancer. Maybe autoimmune diseases generally too? So perhaps it's 1) condition primarily affecting females and 2) invisible (or more accurately able to be rendered invisible) illness. Or that might simply be "the exception that confirms the rule".

 

[Ash]

I don’t know this, it’s a very uneducated guess on my part, but I think that the connection between EDS and ME maybe;

One refusal to diagnose/investigate EDS leads to systemic symptoms being attributed to ME.

Two the EDS all over body injuries places extra burden upon immune system around the inflammation process and connective tissue dysfunction of digestive tract, possibly other mucus membranes including eyes and nose lining, may allow infections to take hold more easily or to impair the process of recovery.

Or more obviously one condition is likely to lead to others, due to physical illness processes of one disease causing vulnerability to others. Maybe though EDS is a constant vulnerability it may only become unmanageable and lead to morbidity via other environmental assaults so perhaps infections or physical injury. So ME could come first and reveal other underlying vulnerabilities.

Something could trigger ME process which could trigger EDS process in turn. Perhaps via loss of muscle mass that was hold the body together and compensated for or protected from overstretch of other tissues and no longer does. In which case it wouldn’t be ME specifically but anything that would weaken the body.

Or any infection, any serious injury can weaken the body no need for ME to take hold and EDS related deterioration begins. If ME happens also it’s just because the causes are the same.


There have been suggestions made by some suffers I think perhaps a few professionals working in this area too, of potential genetic overlap for having EDS and susceptibility ME in families. So I guess could be ME is not more likely to be triggered as a downstream consequence of EDS complications, but a direct consequence of something else which causes EDS only in some, ME only in some, and both in others. All of it is speculation at this point, because we don’t know anything enough about EDS yet. Even less about ME.

Or it maybe that EDS is causing morbidity in a population said to be extremely small but actually larger than thought. ME is a relatively common illness and maybe even much no more so than currently known. In which case the association may be simply be the expected overlap in numbers between two conditions, one common which is bound to happen statistically.

We will wait and see I guess. The same as with any other disease possibly some increase risk of overlap possibly none at all.

I do know that people with ME and people with EDS are all currently having an awful time in the healthcare system. Struggling with untreated, under investigated or un-investigated symptoms. These this practice of care denial and abuse is unimaginable, suffering, sorrow and death. To people with EDS and people with ME. We undoubtedly share this. So I am all for solidarity and joining forces to defend ourselves.

I have joint hyper-mobility, various systemic issues common to people with EDS and have been denied genetic tests to rule in or out EDS. I have, ME severely affected. So of course this affects my view. However I feel the exact same way about all the other genetic conditions that share we are not being test for before being diagnosed with ME a virtually bared from further medical investigation.


Edit: I made word omissions and typos that made this read in two paragraphs as if I was concluding that there was a connection or that genetic EDS was actually common rather than, more common than currently known.

 

[Trish]

Research on prevalence of EDS in ME/CFS is very variable both in quality and in results. Some studies that I would consider more reliable don't show any statistical association between the two. Others claim an association, but when you look closely, use a self diagnosed Beignton score and call it EDS, and also don't do proper epidemiological sampling to rule out self selection bias.

Vascular EDS is rare, but having bendy joints is very common. I think we need to be careful about making assumptions about there being any more than a natural overlap when bendy joints are so common, so there are bound to be lots of people with ME/CFS who have bendy joints.

 

[Ash]

That's one of the reasons I've tried to be very open about this with medical colleagues, and help get the message out. I would hope I have sufficient pre-existing credibility to counter the narrative. However, I think it's still potentially very easy for people to re-pigeonhole someone and simply forget or reframe their prior knowledge of them.

I would note that there is at least one condition primarily affecting females and rarely affecting males that does not suffer from this credibility problem at all: breast cancer. Maybe autoimmune diseases generally too? So perhaps it's 1) condition primarily affecting females and 2) invisible (or more accurately able to be rendered invisible) illness. Or that might simply be "the exception that confirms the rule".

I think it is the exception that proves the rule in some respects. But I think there are other factors, I can’t do justice to right now, but would be like to return to. One comparison often made is between prostate and breast cancer. This is misleading as apples to oranges. An intimate internal area to an external one. Still vulnerable and sensitive but not internal. Testicular and penile cancer are also sometimes invoked as a comparison. The closest you could get would be vulvular or ovarian.

Research on prevalence of EDS in ME/CFS is very variable both in quality and in results. Some studies that I would consider more reliable don't show any statistical association between the two. Others claim an association, but when you look closely, use a self diagnosed Beignton score and call it EDS, and also don't do proper epidemiological sampling to rule out self selection bias.

Vascular EDS is rare, but having bendy joints is very common. I think we need to be careful about making assumptions about there being any more than a natural overlap when bendy joints are so common, so there are bound to be lots of people with ME/CFS who have bendy joints.

Sure but I think I covered all that with multiple proposals that mostly came down to the same overlap that could occur with any illness.

I was also specifically talking about genetic EDS. Something people usually only usually get diagnosed with after fighting along time sudden life threatening complications. Or they’re first degree relatives suffering this before them.

Often people are put into the bin of ME or Fibromyalgia first. Misdiagnosed.


So I think it’s helpful and important to not leave speculation, to those convinced that there is a specific connection and not either to those who think- with our lack of knowledge in both conditions -we can be certain that there isn’t one. It’s an open question.

Just like any other illness which some individuals are at increased risk for, or not at all.

The connection might only be that patients with a poorly treated or untreated disease just will get more of certain common symptoms than other people with no disease or one better managed by medical professionals.

I personally think that last bit of common ground is gonna apply the many many conditions where medical professionals are currently dodging their responsibilities toward patients.

 

[Tilly]

Research on prevalence of EDS in ME/CFS is very variable both in quality and in results. Some studies that I would consider more reliable don't show any statistical association between the two. Others claim an association, but when you look closely, use a self diagnosed Beignton score and call it EDS, and also don't do proper epidemiological sampling to rule out self selection bias.

Vascular EDS is rare, but having bendy joints is very common. I think we need to be careful about making assumptions about there being any more than a natural overlap when bendy joints are so common, so there are bound to be lots of people with ME/CFS who have bendy joints.

This is the reason we need good solid data on it all. Bendy joints (especially if a ME patient becomes more bendy) , POTS, Mast Cell or autoimmune. The Beignton score is outdated and only should ever have been used in research. We have now missed decades of data that would have shown us the real picture on biased opinion of DRs.

The other issue to be considered is how many people have been dismissed or accused of FII or fabricating in themselves. There have been many that have come to light recently. The connection between autistic/nerodivergent and hEDS is now considered a known.

If EDS Drs and Drs in general dismiss ME/cfs then no connection with data will be made ? https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7711487/ in this there is a mention of CFS but have yet to fully digest all this, so that I may ask the questions at a meeting I am to attend. https://pubmed.ncbi.nlm.nih.gov/10926298/ no data means we have to ask the questions to pull in the data in that maybe relevant, based on the lived experiences of those that get ignored - that of our silenced children and their families.

There is a big push to get data from those accused of FII, as those now allowed to attend the Family Courts are deeply troubled and concerned over the handling of FII cases with complex medical conditions. I am asking for cold cases to be the basis of our understanding of what has happened giving outcomes of such cases. The now age appropriate young people are speaking up and are now able to tell their lived experience, this will pull the data out and give us a good picture of the reality of both views of Drs and their opinion causing problems in not only in court but also in all areas of life for young people leading to better research.

 

[Trish]

now age appropriate young people are speaking up and are now able to tell their lived experience, this will pull the data out and give us a good picture of the reality of both views of Drs and their opinion causing problems in not only in court but also in all areas of life for young people leading to better research.

Thank you for your work on this. I'm pleased to hear some of the young people who have been through the FII situation are feeling able to provide information that can be used in research. It's such a horrifying situation, my heart goes out to all the families involved.

 

[Ash]

This is the reason we need good solid data on it all. Bendy joints (especially if a ME patient becomes more bendy) , POTS, Mast Cell or autoimmune. The Beignton score is outdated and only should ever have been used in research. We have now missed decades of data that would have shown us the real picture on biased opinion of DRs.

The other issue to be considered is how many people have been dismissed or accused of FII or fabricating in themselves. There have been many that have come to light recently. The connection between autistic/nerodivergent and hEDS is now considered a known.

If EDS Drs and Drs in general dismiss ME/cfs then no connection with data will be made ? https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7711487/ in this there is a mention of CFS but have yet to fully digest all this, so that I may ask the questions at a meeting I am to attend. https://pubmed.ncbi.nlm.nih.gov/10926298/ no data means we have to ask the questions to pull in the data in that maybe relevant, based on the lived experiences of those that get ignored - that of our silenced children and their families.

There is a big push to get data from those accused of FII, as those now allowed to attend the Family Courts are deeply troubled and concerned over the handling of FII cases with complex medical conditions. I am asking for cold cases to be the basis of our understanding of what has happened giving outcomes of such cases. The now age appropriate young people are speaking up and are now able to tell their lived experience, this will pull the data out and give us a good picture of the reality of both views of Drs and their opinion causing problems in not only in court but also in all areas of life for young people leading to better research.

Hey @Tilly I may have misunderstood, but if your work covers lots of people with EDS and or hyper mobility management and that condition is your area, can you recommend any reliable resources like books perhaps for me to learn about this from?

 

[Tilly]

Hey @Tilly I may have misunderstood, but if your work covers lots of people with EDS and or hyper mobility management and that condition is your area, can you recommend any reliable resources like books perhaps for me to learn about this from?

These conditions are only my area in my advocacy work. I am no a professional in any meaningful sense of the word just a mum (and I like that term "just a mum" it should hold a lot of weight and clout) with experience of others who are mistreated, face Family Court and a broke system.

The recommendations need to based on if you are asking as a professional who wants to learn more or a person who has an interest for a family member or friend as the two need to be handled in different ways but for the same reason, they are discouraged from finding facts to help support those who have needs due to the conditions they have.

 

[Jonathan Edwards]

Can I ask where the reference to more common in females comes from?

EDS is by definition not more common in females because it is either autosomal dominant (unrelated to sex) or sex-linked recessive (i.e. almost exclusively inmates).

As far as I can see this paper simply adds some detail to the longstanding knowledge that people with EDS are more at risk of bleeding from minor trauma.