Wanted: rapid test to prevent deep vein thrombosis

Interview with Prof. Albert Sickmann, Director of Bioanalysis and Chief Executive Officer, Leibniz Institute for Analytical Sciences (German: Leibniz-Institut für Analytische Wissenschaften), ISAS


Photo: Prof. Albert Sickmann

Prof. Albert Sickmann; ©ISAS

Deep vein thrombosis is not just a risk factor for frequent flyers but also for wearers of cardiovascular implants and newly operated patients. Blood thinners prevent these dangerous blood clots from forming, but they need to be carefully adjusted and do not work the same way in every patient. A detailed analysis of platelets (thrombocytes) could prevent complications in the future.

Heart attacks, strokes, and pulmonary embolism can develop when deep vein thrombosis obstructs blood vessels. In the interview with MEDICA.de, Prof. Albert Sickmann talks about what we actually know about platelets and the regulation of blood coagulation. He manages a new research project meant to produce a rapid test for comprehensive platelet diagnostics.

Prof. Sickmann, what is the goal of the project titled "Strategy for the personalized early diagnosis, prevention and monitoring of cardiovascular disease treatments"?

Prof. Albert Sickmann: The basic idea of our project is to measure certain platelet parameters and thus determine their activation or inhibition state. This measurement should ultimately provide a conclusion on whether there is a patient-specific platelet dysfunction that can cause deep vein thrombosis. Even though we know several dozen factors that determine the inhibition and activation of platelets, we are not yet able to measure them simultaneously at this point. And this is the novel part about this project.

Why is this so important for clinical diagnostics?

Sickmann: Each year, between 100,000 and 150,000 patients develop deep vein thrombosis in Germany. They become chronically ill and need to permanently take blood thinners. There is also a risk of thrombosis after surgeries: during postoperative care, one to two percent of patients do not respond to the administered blood thinners as expected. Routinely, only a certain mix of active ingredients that stood the test of time is being administered.

This is a high cost and health-related factor if you assume ten million annual surgeries in Germany. Depending on the severity of the thrombosis, patients need to stay in bed from several days up to one week. Four-tenths to six-tenths of one percent of operated patients dies within 30 days after surgery due to various reasons including deep vein thrombosis. This is also why we focus on patients before and after surgery, on whether we detect a higher risk for them and where it is located.

Grafic: Thrombosis in a blood vessel

Thrombosis can cause stroke, heart attack and pulmonary embolism. Some patients react differently than expected to blood thinners and are at risk because of this; ©panthermedia.net/ rasslava

What is the current state of research and what can be discovered with the help of the platelets?

Sickmann: We know a lot about their activation and inhibition. A number of drugs are effective in this area, but not all patients respond the same way. This is why a subclassification based on the different blood factors we target makes sense to provide personalized treatment for patients. At the moment, there is only a handful of data to classify patients with, and that is not enough.

So basically, we do not know what healthy platelets look like, what the normal range is and ultimately what the risks are.

Sickmann: Ultimately, we do not know the normal ranges of most thrombocytic proteins. One of our goals is to determine these ranges since we are not able to conduct any meaningful measurements without standards. We would like to achieve this with a larger number of healthy or ordinary test persons.

When you consider standard diagnostic tests for the respective cardiovascular diseases, what would be the benefit of blood platelet-based diagnostics?

Sickmann: In diagnostics, frequently only the platelet activation time is being measured. You are able to determine a shorter or longer clotting time than normal with this method but not what causes the problem. A platelet signaling pathway might not work as it should for example. If we are able to identify the individual components of the platelet activation by combining diagnostics with biochemical or biomedical fundamentals, we are potentially also able to immediately suggest a treatment that acts at the right spot.

Many people take aspirin as a blood thinner for example. Some do not tolerate the active ingredient well or they metabolize it faster or slower. In this case, you could choose another inhibitor that is better processed by the organism for instance.

Photo: Hand holding a soluble pill over a glass of water

Aspirin is taken as a bloodthinner as well; ©panthermedia.net/diego.cervo

How is the project structured?

Sickmann: During the project initiation phase, we set up a laboratory infrastructure that is scheduled to be accredited by mid-2017. In the second phase, we plan to analyze samples from several thousand patients before and after surgery. We are in talks with several major German hospitals where patients are meant to be recruited. To be able to make a statement about normal platelet count ranges and the distribution of risk factors in the population, we also need several hundred samples from healthy, ordinary test persons during this phase. The targeted amount is samples from 3,000-5,000 donors by 2020.

During the third phase that will run in parallel, we will work on increased laboratory automation and an increase in throughput rates. Initially, we still analyze with a mass spectrometry assay to chart and statistically analyze the desired components. Finally, during the fourth phase, the costly laboratory process is meant to be turned into an antibody-based process that is ultimately intended to be made available as a cost-effective rapid test.

Photo: Timo Roth; Copyright: B. Frommann

©B. Frommann

The interview was conducted by Timo Roth and translated from German by Elena O'Meara.