Hemostasis, Coagulation & (Neuro)Vascular Disease

The research in the subtheme coagulation disorders focuses on the fundamental mechanistic understanding, diagnosis, treatment, and prevention of both presentation of blood coagulation disorders, i.e. bleeding and thrombosis.

The combined staff members of the division of Thrombosis and Hemostasis in collaboration with many other research groups in and outside the LUMC perform epidemiological and clinically oriented patient studies on the diagnosis and risk factors for these thrombotic and bleeding disorders, studies that are complemented by preclinical research on the basic mechanisms of coagulation to elucidate:

  1. the structure-function relationships of blood coagulation proteins, the pathophysiology of the bleeding disorders von Willebrand disease and hemophilia
  2. the biological mechanism(s) underlying acquired and genetic risk factors for venous thrombosis
  3. the link between coagulation, tumor progression, and cancer-associated thrombosis.

With these basic research themes, we aim to provide the mechanistic framework that will allow for a better interpretation of the clinical findings, with the overall goal of improving the diagnostic tools, tailoring treatment options, identifying new leads for therapies and developing novel patient-focused clinical pathways for short and long-term follow-up. With this central role the Thrombosis and Hemostasis research program contributes to the synergy in the  Cardiovascular theme with strong links to other research programs (clinical, translational and fundamental) within this research theme as well as to research programs within others themes. Lately, special attention is given to the important role of coagulation problems in COVID-19 patients, and the complications associated with  these problems, leading to new research activities directed at improving the treatment and prognosis of COVID-19 patients.

Another important aspect in the cardiovascular theme are the vascular complications related to acute stroke. With the introduction of endovascular treatment, the chances of a good clinical outcome for acute ischemic stroke patients have doubled over the last years. Treatment efficacy sharply declines with time and must therefore be given as soon as possible (time =brain). Pre-hospital selection to fasten the chain of acute stroke care and advanced neuroimaging techniques to select treatment eligible patients are increasingly important. This requires a whole new organization structure in the chain of acute stroke care. In the field of small vessel disease, the advent of high (3T) and ultra-high (7T) field MRI has made detailed imaging of the brain possible. Different small vessel diseases seem to have a distinctive fingerprint of imaging markers. The age-related small vessel disease (SVD) Cerebral Amyloid Angiopathy (CAA) is one of the major causes of intracerebral hemorrhages and cognitive decline in the elderly. Understanding the pathophysiology of the different types of SVD will result in better opportunities for prevention and (neuroprotective) treatment. The LUMC stroke research group focusses on the following topics:

  1. Pathophysiology; factors leading to acute ischemic or hemorrhagic stroke are being studied, such as amyloid angiopathy, intracranial atherosclerosis, carotid arterial atherosclerosis, vessel pulsatility and plaque stability in preclinical (vessel on a chip) and clinical (imaging) models with special emphasis on sex differences.
  2. Prehospital triage; new tools for a rapid discriminative diagnosis of the type of stroke (hemorrhagic or ischemic) investigated for example clinical prediction models and biomarkers based on small non-coding RNA detection.
  3. Imaging; neuroimaging markers that relate to treatment outcome after ischemic stroke are studied with state-of-the-art volumetric CT scans. Advanced and experimental MRI sequences are being investigated to study pathophysiological processes that occur in the immediate post-stroke period (e.g. inflammation, microcirculation) and to learn more about pathophysiological process (e.g. inflammation, lymphatics) – and their relation with vascular-mediated tissue injury - that occur at the start and at later stages of SVDs.
  4. Current and Innovative treatments and E-health; based on insights obtained in our pathophysiologic research new treatments are developed and tested in randomized controlled trials such as the multicenter TRUTH study, Vagus nerve stimulation in acute ischemic stroke and minocycline administration in hereditary (“Katwijkse ziekte”) and sporadic CAA. E-health tools, such as the Stroke Box, are developed.