A descriptive investigation of the ultrastructure of fibrin networks in thrombo-embolic ischemic stroke.

Stroke is one of the leading causes of death worldwide. Formation of a fibrin clot is controlled by a group of tightly regulated plasma proteases and cofactors and a change in the fibrin fiber formation causes an alteration in clot morphology. This plays an important role during thrombotic events. In the current study we investigated the ultrastructure of fibrin networks from fifteen ischemic stroke patients by using scanning electron microscopy. Clot morphology was investigated with and without the addition of human thrombin to the platelet rich plasma. Previously it was shown that, when studying the ultrastructure of fibrin networks, the addition of thrombin is necessary to form an expansive, fully coagulated layer of fibers. Results from the addition of thrombin to the plasma showed thick, matted fibrin fibers and a net covering some of the major fibers in stroke patients. Typical control morphology with major thick fibers and minor thin fibers could be seen in some areas in the stroke patients. In stroke patients, without the addition of thrombin, a matted fibrin network still formed, indicating that the factors responsible for the abnormal fibrin morphology are present in the circulating plasma and is the cause of the observed matted, layered morphology. This is not present in healthy individuals. From the results obtained we suggest that this changed morphology might be useful in a screening regime to identify the possibility of a stroke or even to follow the progress of stroke patients after treatment.

COVID-19-associated coagulopathy and antithrombotic agents-lessons after 1 year.

COVID-19 is associated with a high incidence of thrombotic complications, which can be explained by the complex and unique interplay between coronaviruses and endothelial cells, the local and systemic inflammatory response, and the coagulation system. Empirically, an intensified dose of thrombosis prophylaxis is being used in patients admitted to hospital with COVID-19 and several guidelines on this topic have been published, although the insufficiency of high quality and direct evidence has led to weak recommendations. In this Viewpoint we summarise the pathophysiology of COVID-19 coagulopathy in the context of patients who are ambulant, admitted to hospital, and critically ill or non-critically ill, and those post-discharge from hospital. We also review data from randomised controlled trials in the past year of antithrombotic therapy in patients who are critically ill. These data provide the first high-quality evidence on optimal use of antithrombotic therapy in patients with COVID-19. Pharmacological thromboprophylaxis is not routinely recommended for patients who are ambulant and post-discharge. A first ever trial in non-critically ill patients who were admitted to hospital has shown that a therapeutic dose of low-molecular-weight heparin might improve clinical outcomes in this population. In critically ill patients, this same treatment does not improve outcomes and prophylactic dose anticoagulant thromboprophylaxis is recommended. In the upcoming months we expect numerous data from the ongoing antithrombotic COVID-19 studies to guide clinicians at different stages of the disease.