Tag: thrombosis

Three new papers published – part II

~ BS

In my last post, I explained why I am at the moment not writing one post per new paper. Instead, I group them. This time with a common denominator, namely the role of cardiac troponin and stroke:

High-Sensitivity Cardiac Troponin T and Cognitive Function in Patients With Ischemic Stroke. This paper finds its origins in the PROSCIS study, in which we studied other biomarkers as well. In fact, there is a whole lot more coming. The analyses of these longitudinal data showed a – let’s say ‘medium-sized’ – relationship between cardiac troponin and cognitive function. A whole lot of caveats – a presumptive learning curve, not a big drop in cognitive function to work with anyway. After all, these are only mild to moderately affected stroke patients.

Association Between High-Sensitivity Cardiac Troponin and Risk of Stroke in 96 702 Individuals: A Meta-Analysis. This paper investigates several patient populations -the general population, increased risk population, and stroke patients. The number of patients individuals in the title might, therefore, be a little bit deceiving – I think you should really only look at the results with those separate groups in mind. Not only do I think that the biology might be different, the methodological aspects (e.g. heterogeneity) and interpretation (relative risks with high absolute risks) are also different.

Response by Siegerink et al to Letter Regarding Article, “Association Between High-Sensitivity Cardiac Troponin and Risk of Stroke in 96 702 Individuals: A Meta-Analysis”. We did the meta-analysis as much as possible “but the book”. We pre-registered our plan and published accordingly. This all to discourage ourselves (and our peer reviewers) to go and “hunt for specific results”. But then there was a letter to the editor with the following central point: Because in the subgroup of patients with material fibrillation, the cut-offs used for the cardiac troponin are so different that pooling these studies together in one analysis does not make sense. At first glance, it looks like the authors have a point: it is difficult to actually get a very strict interpretation from the results that we got. This paper described our response. Hint: upon closer inspection, we do not agree and make a good counterargument (at least, that’s what we think).

Three new papers published

~ BS

Normally I publish a new post for each new paper that we publish. But with COVID-19, normal does not really work anymore. But i don’t want to completely throw my normal workflow overboard. Therefore, a quick update on a couple of publications, all in one blogpost, yet without a common denominator:

Stachulski, F., Siegerink, B. and Bösel, J. (2020) ‘Dying in the Neurointensive Care Unit After Withdrawal of Life-Sustaining Therapy: Associations of Advance Directives and Health-Care Proxies With Timing and Treatment Intensity’, Journal of Intensive Care Medicine A paper about the role of advanced directives and treatment in the neurointensive care unit. Not normally the topic I publish about, as the severity of disease in these patients is luckily not what we normally see in stroke patients.

Impact of COPD and anemia on motor and cognitive performance in the general older population: results from the English longitudinal study of ageing. This paper makes use of the ELSA study – an open-access database – and hinges on the idea that sometimes two risk factors only lead to the progression of disease/symptoms if they work jointly. This idea behind interaction is often “tested” with a simple statistical interaction model. There are many reasons why this is not the best thing to do, so we also looked at biological (or additive interaction).

Thrombo-Inflammation in Cardiovascular Disease: An Expert Consensus Document from the Third Maastricht Consensus Conference on Thrombosis. This is a hefty paper, with just as many authors as pages it seems. But this is not a normal paper – it is the consensus statement of the thrombosis meeting last year in Maastricht. I really liked that meeting, not only because I got to see old friends, but also because of a number of ideas and papers were the product of this meeting. This paper is, of course, one of them. But after this one, some papers on the development of an ordinal outcome for functional status after venous thrombosis. But they will be part of a later blog post.

Finding consensus in Maastricht

~ BS
source https://twitter.com/hspronk

Last week, I attended and spoke at the Maastricht Consensus Conference on Thrombosis (MCCT). This is not your standard, run-of-the-mill, conference where people share their most recent research. The MCCT is different, and focuses on the larger picture, by giving faculty the (plenary) stage to share their thoughts on opportunities and challenges in the field. Then, with the help of a team of PhD students, these thoughts are than further discussed in a break out session. All was wrapped up by a plenary discussion of what was discussed in the workshops. Interesting format, right?

It was my first MCCT, and I had difficulty envisioning how exactly this format will work out beforehand. Now that I have experienced it all, I can tell you that it really depends on the speaker and the people attending the workshops. When it comes to the 20 minute introductions by the faculty, I think that just an overview of the current state of the art is not enough. The best presentations were all about the bigger picture, and had either an open question, a controversial statement or some form of “crystal ball” vision of the future. It really is difficult to “find consensus” when there is no controversy as was the case in some plenary talks. Given the break-out nature of the workshops, my observations are limited in number. But from what I saw, some controversy (if need be only constructed for the workshop) really did foster discussion amongst the workshop participants.

Two specific activities stand out for me. The first is the lecture and workshop on post PE syndrome and how we should able to monitor the functional outcome of PE. Given my recent plea in RPTH for more ordinal analyses in the field of thrombosis and hemostasis – learning from stroke research with its mRS- we not only had a great academic discussion, but made immediately plans for a couple of projects where we actually could implement this. The second activity I really enjoyed is my own workshop, where I not only gave a general introduction into stroke (prehospital treatment and triage, clinical and etiological heterogeneity etc) but also focused on the role of FXI and NETS. We discussed the role of DNase as a potential for co-treatment for tPA in the acute setting (talking about “crystal ball” type of discussions!). Slides from my lecture can be found here (PDF). An honorable mention has to go out to the PhD students P and V who did a great job in supporting me during the prep for the lecture and workshop. Their smart questions and shared insights really shaped my contribution.

Now, I said it was not always easy to find consensus, which means that it isn’t impossible. In fact, I am sure that themes that were discussed all boil down to a couple opportunities and challenges. A first step was made by HtC and HS from the MCCT leadership team in the closing session on Friday which will proof to be a great jumping board for the consensus paper that will help set the stage for future research in our field of arterial thrombosis.

Virchow’s triad and lessons on the causes of ischemic stroke

~ BS

I wrote a blog post for BMC, the publisher of Thrombosis Journal in order to celebrate blood clot awareness month. I took my two favorite subjects, i.e. stroke and coagulation, and I added some history and voila!  The BMC version can be found here.

When I look out of my window from my office at the Charité hospital in the middle of Berlin, I see the old pathology building in which Rudolph Virchow used to work. The building is just as monumental as the legacy of this famous pathologist who gave us what is now known as Virchow’s triad for thrombotic diseases.

In ‘Thrombose und Embolie’, published in 1865, he postulated that the consequences of thrombotic disease can be attributed one of three categories: phenomena of interrupted blood flow, phenomena associated with irritation of the vessel wall and its vicinity and phenomena of blood coagulation. This concept has now been modified to describe the causes of thrombosis and has since been a guiding principle for many thrombosis researchers.

The traditional split in interest between arterial thrombosis researchers, who focus primarily on the vessel wall, and venous thrombosis researchers, who focus more on hypercoagulation, might not be justified. Take ischemic stroke for example. Lesions of the vascular wall are definitely a cause of stroke, but perhaps only in the subset of patient who experience a so called large vessel ischemic stroke. It is also well established that a disturbance of blood flow in atrial fibrillation can cause cardioembolic stroke.

Less well studied, but perhaps not less relevant, is the role of hypercoagulation as a cause of ischemic stroke. It seems that an increased clotting propensity is associated with an increased risk of ischemic stroke, especially in the young in which a third of main causes of the stroke goes undetermined. Perhaps hypercoagulability plays a much more prominent role then we traditionally assume?

But this ‘one case, one cause’ approach takes Virchow’s efforts to classify thrombosis a bit too strictly. Many diseases can be called multi-causal, which means that no single risk factor in itself is sufficient and only a combination of risk factors working in concert cause the disease. This is certainly true for stroke, and translates to the idea that each different stroke subtype might be the result of a different combination of risk factors.

If we combine Virchow’s work with the idea of multi-causality, and the heterogeneity of stroke subtypes, we can reimagine a new version of Virchow’s Triad (figure 1). In this version, the patient groups or even individuals are scored according to the relative contribution of the three classical categories.

From this figure, one can see that some subtypes of ischemic stroke might be more like some forms of venous thrombosis than other forms of stroke, a concept that could bring new ideas for research and perhaps has consequences for stroke treatment and care.

Figure 1. An example of a gradual classification of ischemic stroke and venous thrombosis according to the three elements of Virchow’s triad.

However, recent developments in the field of stroke treatment and care have been focused on the acute treatment of ischemic stroke. Stroke ambulances that can discriminate between hemorrhagic and ischemic stroke -information needed to start thrombolysis in the ambulance-drive the streets of Cleveland, Gothenburg, Edmonton and Berlin. Other major developments are in the field of mechanical thrombectomy, with wonderful results from many studies such as the Dutch MR CLEAN study. Even though these two new approaches save lives and prevent disability in many, they are ‘too late’ in the sense that they are reactive and do not prevent clot formation.

Therefore, in this blood clot awareness month, I hope that stroke and thrombosis researchers join forces and further develop our understanding of the causes of ischemic stroke so that we can Stop The Clot!

ECTH 2016

~ BS

ecth-small-logo
ecth2016.org

Last week was the first edition of the European Congress on Thrombosis and Hemostasis in the Hague (NL). The idea of this conference is to provide a platform for european thrombosis researchers and doctors to meet in the dull years between ISTH meetings. There is a strong emphasis on enabling and training the young researchers, as can be from the different activities and organisational aspects. One os these things was the Junior advisory board, of which I was part. We had the task to give advice both solicited and unsolicited, and help organise and shape some of the innovative aspects. For example: we had the so-called fast and furious sessions, where authors of the best abstract were asked to let go of the standard presentation format and share their research TED talk style.

I learned a lot during these sessions, and even got in contact with some groups that have interesting methods and approaches that we might apply in our studies and patient populations. My thoughts: targeting FXII and FXI as well as DNAse treatment are the next big thing. We also had a great selection of speakers for meet-the-experts and how-to sessions. These sessions demanded active participation of all participants which is really a great way to build new collaborations and friendships.

The 5K fun run with 35+ participants was also a great succes.

The wednesday plenary sessions, including the talks on novel and innovative methods of scholarly communications as well as the very well received sessions from Malcolm Macloud on reducing research waste where inspiring to all. Missed it? do not worry, they have shared their slides online!

All in all, the conference was a great success in both numbers (750+ participants) as well as scientific quality. I am looking forward to the next edition, which will be held in Marseille in two years time. Hope to see you all there!

The ECTH 2016 in The Hague

~ BS

My first conference experience (ISTH 2008, Boston) got me hooked on science. All these people doing the same thing, speaking the same language, and looking to show and share their knowledge. This is true when you are involved in the organisation. Organising the international soccer match at the Olympic stadium in Amsterdam linked to the ISTH 2013 to celebrate the 25th anniversary of the NVTH was fun. But lets not forget the exciting challenge of organising the WEON 2014.

And now, the birth of a new conference, the European Congress of Thrombosis and Hemostasis, which will be held in The Hague in Netherlands (28-30 sept 2016). I am very excited for several reasons: First of all, this conference will fill in the gap of the bi-annual ISTH conferences. Second, I have the honor to help out as the chair of the junior advisory board. Third, the Hague! My old home town!

So, we have 10 months to organise some interesting meetings and activities, primary focussed on the young researchers. Time to get started!

New article published: the relationship between ADAMTS13 and MI

~ BS

2015-06-16 14_26_12-Plasma ADAMTS13 levels and the risk of myocardial infarction_ an individual pati

this article is a collaboration with a lot of guys. initiated from the Milan group, we ended up with a quite diverse group of researchers to answers this question because of the methods that we used: the individual patient data meta-analysis. The best thing about this approach: you can pool the data from different studies, even while you can adjusted for potential sources of confounding in a similar manner (given that the data are available, that is). On themselves, these studies showed some mixed results. But in the end, we were able to use the combined data to show that there was an increase MI risk but only for those with very low levels of ADAMTS13. So, here you see the power of IPD meta-analysis!

The credits for this work go primarily to AM who did a great job of getting all PI’s on board, analysing the data and writing a god manuscript. The final version is not online, but you find the pre-publication on pubmed

 

 

New article: the intrinsic coagulation proteins and the risk of arterial thrombosis

~ BS

I got good news today! A manuscript on the role of the intrinsic coagulation factors in the causal mechanisms leading to myocardial infarction and ischaemic stroke has been accepted for publication by the JTH. It took sometime, but in the end I’m very glad that this paper was published in the JTH because its readership is both clinical as well as biomedical: just the place where I feel most at home.

The basic message? These factors do contribute to ischaemic risk, but not to the risk of myocardial infarction. This is mostly the case for coagulation factor XI, which is a nice finding, because it could be a new target for anti-thrombotic therapies.

The article is now in print and will be made available soon. In the mean time, you can refer to my thesis, in which this research was also described.

New article published: review on obesity and venous thrombosis

~ BS

Together with colleagues I worked on a review on the role of obesity as a risk factor for venous thrombosis. I’m second author on the article, which come online last week, and most work has been done by SKB from Norway, who is visiting our department for a full year.

The article is written from an epidemiological point of view and discusses several points that are worth mentioning here. First of all, obesity is an ill-defined concept: are we only talking BMI, or do also other measures of obesity need to be taken into account? Second, even when defined, the results are not always easy to interpret. In causal research there are a couple of things that need to be fulfilled before one can answer the question whether something is risk factor of disease. For example, BMI can be reduced by means of exercise   diet or disease, which all three have completely different effects on thrombosis risk. We discuss all these epidemiological problems, together with the existing body of evidence in the new article in seminars of thrombosis and hemostasis. These question are not only important for our understanding of thrombotic disease, but also to grasp the causal role of obesity in (cardiovascular) disease. This research question has in ast couple of years been put on the research agenda of the NEO study, on which perhaps more in the future.

The article, with the full title “Role of Obesity in the Etiology of Deep Vein Thrombosis and Pulmonary Embolism: Current Epidemiological Insights” can be found via PubMed, or via my personal Mendeley page.