HIND – Hypercoagulability in Neurovascular Disorders

• Coagulation factors of the intrinsic coagulation pathway are known to contribute to increased clotting propensity (hypercoagulability), but their role in ischemic stroke had not yet been explored in detail.
• Recently, an association between elevated levels of coagulation factor XI (of the intrinsic pathway) and an increased risk for ischemic stroke and other vascular events was demonstrated. Furthermore, promising new research implicated targeting intrinsic coagulation pathway factors in the context of anticoagulation therapy.
• A dose-dependent association has been observed between elevated levels of coagulation factor VIII and thrombosis. Elevated levels of factor VIII indicate increased clotting activity, and we hypothesized these levels may lead to small clots in the brain, and in turn, and small regions of tissue death, visible on MRI scans as white matter lesions. This may be of particular relevance since research has linked covert white matter lesions to diminished cognitive function in the general population.

At the time of project conception, it was unclear whether hypercoagulability…

• affects ischemic stroke recurrence
• has a differential effect on the risk for different subtypes of stroke
• plays a role in the development of white matter lesions and subsequent cognitive impairment

Therefore, our scientific aim was to elucidate the role of hypercoagulability in the etiological mechanisms of neurovascular disorders in three subprojects to address these three points.

Genetic determinants of activity and antigen levels of contact system factors.
Rohmann JL, de Haan HG, Algra A, Vossen CY, Rosendaal FR, Siegerink B.
J Thromb Haemost 2019; 17: 157–68.
PMID: 30288888
DOI: 10.1111/jth.14307

Coagulation factor XII, XI, and VIII activity levels and secondary events after first ischemic stroke.
Rohmann JL, Huo S, Sperber PS, Piper SK, Rosendaal FR, Heuschmann PU, Endres M, Liman TG, Siegerink B.
J Thromb Haemost 2020.
PMID: 32935900
DOI: 10.1111/jth.15092

Coagulation factor VIII, white matter hyperintensities and cognitive function: Results from the Cardiovascular Health Study.
Rohmann JL, Longstreth WT Jr, Cushman M, Fitzpatrick AL, Heckbert SR, Rice K, Rosendaal FR, Sitlani CM, Psaty BM, Siegerink B.
PLoS One2020; 15: e0242062.
PMID: 33196677
DOI: 10.1371/journal.pone.0242062

Our research involved the analysis of prospective data from multiple ongoing studies including our own PROSCIS-B at the CSB and two large international studies (the US Cardiovascular Health Study and the Dutch RATIO study).

Jessica Rohmann, MScPH, PhD Candidate
Bob Siegerink, PhD

Project research began in June 2015. Project completed in December 2020.