PROJECT: JTC2022 - Cerebrovascular: COHDICH

Cerebral microhaemorrhages (CMHs) are predictors of future intracerebral haemorrhage (ICH). While CMHs are mainly seen as markers of the underlying vessel disease, to what extent haemostatic disorders influence CMH incidence and transformation into ICH remains unclear. Congenital haemostatic defects are unique situations, in which ICH is frequent and devastating. Hypothesis: In the setting of CMHs, the existence of a haemostatic disorder promotes macrobleeding, and modulates the inflammatory response around the bleeding when a macrobleeding occurs. COHDICH offers a translational approach from animal models with severe haemostatic defects to patients with cerebral bleedings. In workpackage 1, we will: (i) determine the prevalence of CMHs in patients with severe haemostatic defects related to the coagulation cascade (haemophilia) or primary haemostasis (von Willebrand disease, vWD), and (ii) evaluate the influence of impaired haemostasis on the inflammatory response around ICH. In workpackage 2, we will induce CMHs in mouse models for haemophilia and VWD, and explore their transformation into ICHs. In addition, we will study the role of these haemostatic defects in perspective of the inflammatory response around the bleeding. Relevance to public health: Identifying predictors of future cerebral bleedings is of utmost importance and may lead to a change in patients’ preventive treatment regimen. COHDICH fills a knowledge gap and could pave the way to new treatments.