Short summary

The study purpose is to identify new risk markers for arterial and venous thrombosis in patients who had a thrombosis in the past. These new biomarkers will be used to identify patients at particularly high risk of thrombosis number two, and in these high-risk patients a targeted preventive treatment will be initiated. Today, it is not possible to identify these high-risk patients. Another purpose of the project is to investigate whether the identified risk markers differ in subgroups, e.g. in overweight patients.

Rationale

Blood clotting disorders are frequent causes of mortality and morbidity in the western world. In 2015, approximately 9,000 Danes were affected by a thrombosis in the heart and 14,000 by a stroke in the brain. Deep venous thrombosis, which can result in life-threatening pulmonary embolism, affects approximately 4,000 Danes each year. Treatment has improved significantly over the past years, and a large number of patients survive both arterial and venous thrombosis. In 2015, the number of survivors were 53,000 patients with an arterial thrombosis in the heart, 87,000 patients with a stroke, and 30,000 patients with a venous thrombosis in the legs.

Both arterial and venous thrombotic diseases are multifactorial, and the interaction between several risk factors is important for the development of the diseases. Although many risk factors are well described, there is still a need to identify new and more specific risk factors. An important and unresolved question is why a large proportion of patients experience thrombosis number two while others do not. Identification of new risk factors will help to elucidate the pathophysiological mechanisms that lead to recurrent thrombosis, including whether arterial and venous thromboses can be perceived as different, or whether the risk factors reflect a common pathophysiological mechanism. It is also important to uncover whether the mechanisms (and risk factors) are the same in subgroups of patients, e.g. in overweight patients. It has previously been shown that the risk of recurrence of venous thrombosis is higher in men than in women and depends on body weight.

The balance between blood clot formation (coagulation) and blood clot dissolution (fibrinolysis) plays a central role for the thrombotic risk. Several studies have investigated the importance of single factors in this hemostatic balance for the risk of recurrent thrombosis, but the results are conflicting. Since 1995, the Thrombosis Clinic at the Department of Clinical Biochemistry, University Hospital of Southern Denmark has seen more than 5,000 patients diagnosed with venous or arterial thrombosis. Patients have provided blood samples for future research projects (a biobank). Because these investigations include a large number of patients and follow a standardized procedure, the information obtained is particularly suitable for research purposes. Therefore, we aim to establish a research database including the informations provided by the patient investigations. In this context, it is necessary to retrieve information in the patients' electronic records, where information on the patients' medical history, family history, medication, and laboratory results are recorded at the time of investigation. 

Hopefully, our new database will become a useful tool for understanding mechanisms and risk profiles. In order to identify new risk markers, a longitudinal perspective must be added to the study. We therefore plan to follow up with the "Sundhedsdatastyrelsen" to find out whether patients had a second thrombosis since the first health examination took place.

Thus, the purpose of our project is to identify new and better risk markers for arterial and venous thrombosis in patients who already had a thrombosis in the past. These new biomarkers will be used to identify patients at particularly high risk of thrombosis number two, and in these high-risk patients a targeted preventive treatment will be initiated. Today, it is not possible to identify these high-risk patients. Another purpose of the project is to investigate whether the identified risk markers differ in subgroups, e.g. overweight patients.

Description of the cohort

The cohort includes information on 1600 patients (men and women) investigated between 1995 and 2013 and who were 18-50 years old at the time of the clinical investigation ("younger patients"). Patients were diagnosed with arterial thrombosis, venous thrombosis, or bleeding

Data and biological material

For each patient, the following informations were recorded: family history of thrombosis, height, weight, waist circumference, blood pressure, medications, gender, age, educational level, and biochemical laboratory results related to coagulation and fibrinolysis measured in blood samples.