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

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!

Associate editor at BMC Thrombosis Journal


In the week just before Christmas, HtC approached me by asking whether or not I would like to join the editorial board of BMC Thrombosis Journal as an Associate Editor. the aims and scope of the journal, taken from their website:

“Thrombosis Journal  is an open-access journal that publishes original articles on aspects of clinical and basic research, new methodology, case reports and reviews in the areas of thrombosis.Topics of particular interest include the diagnosis of arterial and venous thrombosis, new antithrombotic treatments, new developments in the understanding, diagnosis and treatments of atherosclerotic vessel disease, relations between haemostasis and vascular disease, hypertension, diabetes, immunology and obesity.”

I talked to HtC, someone at BMC, as well as some of my friends and colleagues whether or not this would be a wise thing to do. Here is an overview of the points that came up:

Experience: Thrombosis is the field where I grew up in as a researcher. I know the basics, and have some extensive knowledge on specific parts of the field. But with my move to Germany, I started to focus on stroke, so one might wonder why not use your time to work with a stroke related journal. My answer is that the field of thrombosis is a stroke related field and that my position in both worlds is a good opportunity to learn from both fields. Sure, there will be topics that I have less knowledge off, but here is where an associate editor should rely on expert reviewers and fellow editors.

This new position will also provide me with a bunch of new experiences in itself: for example, sitting on the other side of the table in a peer review process might help me to better understand a rejection of one of my own papers. Bottom line is that I think that I both bring and gain relevant experiences in this new position.

Time: These things cost time. A lot. Especially when you need to learn the skills needed for the job, like me. But learning these skills as an associate editor is an integral part of the science apparatus, and I am sure that the time that I invest will help me develop as a scientist. Also, the time that I need to spend is not necessary the type of time that I currently lack, i.e. writing time. For writing and doing research myself I need decent blocks of time to dive in and focus  — 4+ hours if possible. The time I need to perform my associate editor tasks is more fragmented: find peer reviewers, read their comments and make a final judgement are relative fragmented activities and I am sure that as soon as I get the hang of it I can squeeze those activities within shorter slots of time. Perhaps a nice way to fill those otherwise lost 30 minutes between two meetings?

Open science: Thrombosis journal is part of the Biomed central family. As such, it is an 100% OA journal. It is not that I am an open science fanboy or sceptic, but I am very curious how OA is developing and working with an OA journal will help me to understand what OA can and cannot deliver.

Going over these points, I am convinced that I can contribute to the journal with my experience in the fields of coagulation, stroke and research methodology. Also, I think that the time that it will take to learn the skills needed are an investment that in the end will help me to grow as a researcher. So, I replied HtC with a positive answer. Expect email requesting for a peer review report soon!