Besides mediating hemostatic functions, platelets are increasingly recognized as important players of inflammation. Data from experiments in mice and men revealed various intersection points between thrombosis, hemostasis, and inflammation, which are addressed and discussed in this review in detail. One such example is the intrinsic coagulation cascade that is initiated after platelet activation thereby further propagating and re-enforcing wound healing or thrombus formation but also contributing to the pathophysiology of severe diseases. FXII of the intrinsic pathway connects platelet activation with the coagulation cascade during immune reactions. It can activate the contact system thereby either creating an inflammatory state or accelerating inflammation. Recent insights into platelet biology could show that platelets are equipped with complement receptors. Platelets are important for tissue remodeling after injury has been inflicted to the endothelial barrier and to the subendothelial tissue. Thus, platelets are increasingly recognized as more than just cells relevant for bleeding arrest. Future insights into platelet biology are to be expected. This research will potentially offer novel opportunities for therapeutic intervention in diseases featuring platelet abundance.

Background This study analyzed the effects on long‐term outcome of residual mitral regurgitation ( MR ) and mean mitral valve pressure gradient ( MVPG ) after percutaneous edge‐to‐edge mitral valve repair using the MitraClip system. Methods and Results Two hundred fifty‐five patients who underwent percutaneous edge‐to‐edge mitral valve repair were analyzed. Kaplan–Meier and Cox regression analyses were performed to evaluate the impact of residual MR and MVPG on clinical outcome. A combined clinical end point (all‐cause mortality, MV surgery, redo procedure, implantation of a left ventricular assist device) was used. After percutaneous edge‐to‐edge mitral valve repair, mean MVPG increased from 1.6±1.0 to 3.1±1.5 mm Hg ( P <0.001). Reduction of MR severity to ≤2+ postintervention was achieved in 98.4% of all patients. In the overall patient cohort, residual MR was predictive of the combined end point while elevated MVPG >4.4 mm Hg was not according to Kaplan–Meier and Cox regression analyses. We then analyzed the cohort with degenerative and that with functional MR separately to account for these different entities. In the cohort with degenerative MR , elevated MVPG was associated with increased occurrence of the primary end point, whereas this was not observed in the cohort with functional MR . Conclusions MVPG >4.4 mm Hg after MitraClip implantation was predictive of clinical outcome in the patient cohort with degenerative MR . In the patient cohort with functional MR , MVPG >4.4 mm Hg was not associated with increased clinical events.

Platelets contribute to the regulation of tissue neovascularization, although the specific factors underlying this function are unknown. Here, we identified the complement anaphylatoxin C5a-mediated activation of C5a receptor 1 (C5aR1) on platelets as a negative regulatory mechanism of vessel formation. We showed that platelets expressing C5aR1 exert an inhibitory effect on endothelial cell functions such as migration and 2D and 3D tube formation. Growth factor- and hypoxia-driven vascularization was markedly increased in C5ar1−/− mice. Platelet-specific deletion of C5aR1 resulted in a proangiogenic phenotype with increased collateralization, capillarization and improved pericyte coverage. Mechanistically, we found that C5a induced preferential release of CXC chemokine ligand 4 (CXCL4, PF4) from platelets as an important antiangiogenic paracrine effector molecule. Interfering with the C5aR1-CXCL4 axis reversed the antiangiogenic effect of platelets both in vitro and in vivo.In conclusion, we identified a mechanism for the control of tissue neovascularization through C5a/C5aR1 axis activation in platelets and subsequent induction of the antiangiogenic factor CXCL4.

SummaryThere is emerging evidence that platelets have an important role in inflammation beyond their involvement in hemostasis. Platelets can contribute to inflammatory reactions via crosstalk both with immune cells and endothelial cells. Inflamed vessels are characterized by the presence of activated endothelial cells. These activated endothelial cells upregulate receptors necessary for leukocyte recruitment, but also for the adhesion of platelets. Subsequently, immune cells can bind to platelets through adhesion receptors presented on the platelet surface, thus supporting leukocyte recruitment to the vessel wall. There are several neurological diseases associated with vascular inflammation including multiple sclerosis (MS) and stroke. Increased markers of platelet activation could be demonstrated in patients suffering from MS compared to healthy individuals. Reports from murine models indicate that platelets may be of importance for disease progression and severity by mediating leukocyte recruitment as one potential underlying mechanism. Blocking platelet function disease severity was considerably ameliorated. Moreover, processes of tissue remodelling may be influenced by platelet derived mediators. Whether a role of platelets for vascular inflammation can be extrapolated to further neurological diseases will have to be investigated in further in depth experimental and clinical trials.Platelets and platelet associated mechanisms may offer novel starting points to understand neurovascular diseases from a different point of view and to develop novel approaches to access the disease.

In March 2020, the World Health Organization (WHO) declared the novel coronavirus disease pandemic. Here, we present the case of a patient who was admitted to our hospital with acute respiratory distress syndrome (ARDS) following infection with COVID-19. After initial stabilization through restrictive uid management, hemadsorption using Cytosorb® was performed and nally temporary extubation of the patient was possible. However, the patient again clinically deteriorated and needed ventilation and nally ECMO-support and high catecholamine application. Whilst being on VV-ECMO, hemadsorption using Biosky® MG 350 lter was performed. In this manuscript, after a brief overview of the role of hemadsorption in ARDS, a detailed case presentation is followed by a critical discussion of the current literature.