Measuring platelet activation and blood coagulation

When a blood vessel is damaged, the leakage has to be stopped in time, but it is equally important that the repair does not continue until the vessel is completely blocked. The blood platelets play a crucial role in both these events. 

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the world. By adhering and aggregating at the site of vessel damage, blood platelets play a crucial role in the complex chain of events that lead to thrombotic occlusion of the coronary or cerebral artery. This has sparked a great interest in the field of platelet inhibition and inhibitors, in order to develop safe and effective ways to prevent thrombosis. Currently, anti-platelet drugs are one of the biggest sellers on the pharmaceutical market. However, the use of more effective drugs, and also combinations of drugs may lead to serious bleeding complications in some patients, something that has been hard to predict with current methods to study platelet function and blood coagulation. 

My research is focused on the function and physiology of blood platelets. A main theme is to work in the border between technology, biology and medicine to develop and use new methods and technologies to study platelets. During my PhD studies, I was a part of the multidisciplinary graduate school Forum Scientium at Linköping University, where I worked with studies on how the platelets influence blood coagulation, using a new technique called free oscillation rheometry (FOR). This was combined with established methods for platelet function analysis, such as flow cytometry, to be able to gain new insights in the physiology of platelets and their interactions with the blood coagulation.

During a postdoctoral period in Dublin, I was working at the Royal College of Surgeons in Ireland (RCSI) as a part of the Biomedical Diagnostics Institute (BDI) which is a Centre for Science, Engineering and Technology (CSET), supported by Science Foundation Ireland. The research focus was on developing platelet function tests, and we developed a system where microcontact printing is used to evaluate platelet adhesion and function (patent application filed). Using microcontact printing, we have shown that we can make reproducible surfaces with more than 100,000 spots of platelet adhesive proteins, with diameters down to 2 micrometer, i.e. approximately the size of a single circulating platelet. This makes it possible to capture and study single adhering platelets, and to automate quantification of platelet adhesion.

Activated platelets interact with the coagulation system by providing a surface where the coagulation factor complexes can be assembled, which is important to localise coagulation to the site of vessel wall injury. It is known that not all platelets respond in a similar way when activated, and that only a fraction is normally responding with the surface changes needed to support coagulation. In my research, we are examining factors and activation pathways involved in determining the reaction of the individual platelets, using techniques to study individual cells, such as flow cytometry and single cell adhesion platforms. We also use more complex systems such as thrombin generation and whole blood coagulation assays to put the findings into a physiological context.

The general aim of my research is to combine technology and medicine, both with the aim to gain new insights in fundamental platelet physiology and to create benefits for patients suffering from cardiovascular disease and platelet-related disorders. We want to develop better methods to measure platelet function. The ultimate goal is to be able to tell when a patient has received appropriate treatment in order to prevent thrombosis, i.e. unwanted blood coagulation, but still avoiding bleeding complications.