Atherothrombosis is a leading cause of cardiovascular mortality and long-term morbidity. Platelets and coagulation
proteases, interacting with circulating cells and in different vascular beds, modify several complex pathologies including
atherosclerosis. In the second Maastricht Consensus Conference on
Thrombosis, this theme was addressed by diverse scientists from bench to bedside. All presentations were discussed with audience members and the results of these discussions were incorporated in the final document that presents a state-of-the-art reflection of expert opinions and consensus recommendations regarding the following five topics: 1. Risk factors,
biomarkers and plaque instability: In
atherothrombosis research, more focus on the contribution of specific risk factors like ectopic fat needs to be considered; definitions of
atherothrombosis are important distinguishing different phases of disease, including plaque (in)stability; proteomic and metabolomics data are to be added to genetic information. 2. Circulating cells including platelets and
atherothrombosis: Mechanisms of leukocyte and macrophage plasticity, migration, and transformation in murine
atherosclerosis need to be considered; disease mechanism-based
biomarkers need to be identified; experimental systems are needed that incorporate whole-blood flow to understand how red blood cells influence
thrombus formation and stability; knowledge on platelet heterogeneity and priming conditions needs to be translated toward the in vivo situation. 3. Coagulation
proteases,
fibrin(
ogen) and
thrombus formation: The role of factor (F) XI in
thrombosis including the lower margins of this factor related to safe and effective antithrombotic
therapy needs to be established; FXI is a key regulator in linking platelets,
thrombin generation, and inflammatory mechanisms in a
renin-
angiotensin dependent manner; however, the impact on
thrombin-dependent PAR signaling needs further study; the fundamental mechanisms in FXIII biology and biochemistry and its impact on
thrombus biophysical characteristics need to be explored; the interactions of red cells and
fibrin formation and its consequences for
thrombus formation and lysis need to be addressed. Platelet-
fibrin interactions are pivotal determinants of clot formation and stability with potential therapeutic consequences. 4. Preventive and acute treatment of
atherothrombosis and arterial
embolism; novel ways and tailoring? The role of
protease-activated receptor (PAR)-4 vis à vis PAR-1 as target for antithrombotic
therapy merits study; ongoing trials on platelet function test-based antiplatelet
therapy adjustment support development of practically feasible tests; risk scores for patients with
atrial fibrillation need refinement, taking new
biomarkers including coagulation into account; risk scores that consider organ system differences in
bleeding may have added value; all forms of oral
anticoagulant treatment require better organization, including education and emergency access; laboratory testing still needs rapidly available sensitive tests with short turnaround time. 5. Pleiotropy of coagulation
proteases,
thrombus resolution and ischaemia-reperfusion: Biobanks specifically for
thrombus storage and analysis are needed; further studies on novel modified activated
protein C-based agents are required including its cytoprotective properties; new avenues for optimizing treatment of patients with
ischaemic stroke are needed, also including novel agents that modify fibrinolytic activity (aimed at
plasminogen activator inhibitor-1 and
thrombin activatable fibrinolysis inhibitor.