Belgian clinical guidance on anticoagulation management in hospitalised and ambulatory patients with COVID-19

Objectives COVID-19 predisposes patients to thrombotic disease. The aim of this guidance document is to provide Belgian health-care workers with recommendations on anticoagulation management in COVID-19 positive patients. Methods These recommendations were based on current knowledge and a limited level of evidence. Results We formulated recommendations for the prophylaxis and treatment of COVID-related venous thromboembolism in ambulatory and hospitalised patients, as well as recommendations for the use of antithrombotic drugs in patients with prior indication for anticoagulation who develop COVID-19. Conclusions These recommendations represent an easy-to-use practical guidance that can be implemented in every Belgian hospital and be used by primary care physicians and gynaecologists. Of note, they are likely to evolve with increased knowledge of the disease and availability of data from ongoing clinical trials

Two Distinct Coagulase-Dependent Barriers Protect Staphylococcus aureus from Neutrophils in a Three Dimensional in vitro Infection Model

Staphylococcus aureus is a pyogenic abscess-forming facultative pathogenic microorganism expressing a large set of virulence-associated factors. Among these, secreted proteins with binding capacity to plasma proteins (e.g. fibrinogen binding proteins Eap and Emp) and prothrombin activators such as Coagulase (Coa) and vWbp are involved in abscess formation. By using a three-dimensional collagen gel (3D-CoG) supplemented with fibrinogen (Fib) we studied the growth behavior of S. aureus strain Newman and a set of mutants as well as their interaction with mouse neutrophils by real-time confocal microscopy. In 3D-CoG/Fib, S. aureus forms microcolonies which are surrounded by an inner pseudocapsule and an extended outer dense microcolony-associated meshwork (MAM) containing fibrin. Coa is involved in formation of the pseudocapsule whereas MAM formation depends on vWbp. Moreover, agr-dependent dispersal of late stage microcolonies could be observed. Furthermore, we demonstrate that the pseudocapsule and the MAM act as mechanical barriers against neutrophils attracted to the microcolony. The thrombin inhibitor argatroban is able to prevent formation of both pseudocapsule and MAM and supports access of neutrophils to staphylococci. Taken together, this model can simulate specific stages of S. aureus abscess formation by temporal dissection of bacterial growth and recruitment of immune cells. It can complement established animal infection models in the development of new treatment options

Preventing Staphylococcus aureus Sepsis through the Inhibition of Its Agglutination in Blood

Staphylococcus aureus infection is a frequent cause of sepsis in humans, a disease associated with high mortality and without specific intervention. When suspended in human or animal plasma, staphylococci are known to agglutinate, however the bacterial factors responsible for agglutination and their possible contribution to disease pathogenesis have not yet been revealed. Using a mouse model for S. aureus sepsis, we report here that staphylococcal agglutination in blood was associated with a lethal outcome of this disease. Three secreted products of staphylococci - coagulase (Coa), von Willebrand factor binding protein (vWbp) and clumping factor (ClfA) – were required for agglutination. Coa and vWbp activate prothrombin to cleave fibrinogen, whereas ClfA allowed staphylococci to associate with the resulting fibrin cables. All three virulence genes promoted the formation of thromboembolic lesions in heart tissues. S. aureus agglutination could be disrupted and the lethal outcome of sepsis could be prevented by combining dabigatran-etexilate treatment, which blocked Coa and vWbp activity, with antibodies specific for ClfA. Together these results suggest that the combined administration of direct thrombin inhibitors and ClfA-antibodies that block S. aureus agglutination with fibrin may be useful for the prevention of staphylococcal sepsis in humans

Cardiovascular End Points and Mortality Are Not Closer Associated With Central Than Peripheral Pulsatile Blood Pressure Components

Pulsatile blood pressure (BP) confers cardiovascular risk. Whether associations of cardiovascular end points are tighter for central systolic BP (cSBP) than peripheral systolic BP (pSBP) or central pulse pressure (cPP) than peripheral pulse pressure (pPP) is uncertain. Among 5608 participants (54.1% women; mean age, 54.2 years) enrolled in nine studies, median follow-up was 4.1 years. cSBP and cPP, estimated tonometrically from the radial waveform, averaged 123.7 and 42.5 mm Hg, and pSBP and pPP 134.1 and 53.9 mm Hg. The primary composite cardiovascular end point occurred in 255 participants (4.5%). Across fourths of the cPP distribution, rates increased exponentially (4.1, 5.0, 7.3, and 22.0 per 1000 person-years) with comparable estimates for cSBP, pSBP, and pPP. The multivariable-adjusted hazard ratios, expressing the risk per 1-SD increment in BP, were 1.50 (95% CI, 1.33-1.70) for cSBP, 1.36 (95% CI, 1.19-1.54) for cPP, 1.49 (95% CI, 1.33-1.67) for pSBP, and 1.34 (95% CI, 1.19-1.51) for pPP (P<0.001). Further adjustment of cSBP and cPP, respectively, for pSBP and pPP, and vice versa, removed the significance of all hazard ratios. Adding cSBP, cPP, pSBP, pPP to a base model including covariables increased the model fit (P<0.001) with generalizedR(2)increments ranging from 0.37% to 0.74% but adding a second BP to a model including already one did not. Analyses of the secondary end points, including total mortality (204 deaths), coronary end points (109) and strokes (89), and various sensitivity analyses produced consistent results. In conclusion, associations of the primary and secondary end points with SBP and pulse pressure were not stronger if BP was measured centrally compared with peripherally

Rate and duration of hospitalisation for acute pulmonary embolism in the real-world clinical practice of different countries : Analysis from the RIETE registry

publishersversionPeer reviewe

Bacterial killing by platelets: making sense of (H)IT

status: publishe

Concentration-dependent stimulation of cholinergic motor nerves or smooth muscle by [Nle(13)]motilin in the isolated rabbit gastric antrum

In man, rabbit and cat, the effects of motilin and motilides are neurally mediated in vivo, whereas in vitro binding and contractility studies suggest the presence of a smooth muscular receptor. The aim of this study was to investigate in vitro interactions of motilin with the enteric excitatory neurotransmission in the gastric antrum of the rabbit. Circular muscle strips from the pre-pyloric antrum were subjected to electrical field stimulation (1 ms, 1-32 Hz, 10 s train) and muscle twitch responses were recorded isometrically. Induced twitch responses were frequency dependent (1-32 Hz) and entirely neurogenic (tetrodotoxin sensitive). [Nle(13)]motilin dose-dependently (10(-9)-10(-8) M) enhanced the amplitude of, atropine sensitive, evoked contractions. At 4 Hz the response, expressed as a % of the response to 32 Hz, increased from 15.5 +/- 4.1% (control) to 28.1 +/- 5.8% (motiiin 10(-9) M), and to 45.8 +/- 3.6% (motilin 10(-8.5) M) (P < 0.05). This effect was not inhibited by hexamethonium (10(-3.3) M) but was abolished by the motilin receptor antagonist GM-109 (10(-5) M). In unstimulated strips, motilin induced phasic-tonic contractions with a threshold concentration of 10(-8) M and an pEC(50) of 7.48, which were also inhibited by GM-109 (10(-5) M) but not by tetrodotoxin (10(-5.5) M). The maximal tension, frequency and dose-dependency of carbachol-induced contractions were not influenced by motilin (pEC(50), carbachol: 6.48 +/- 0.06 (control), 6.49 +/- 0.07 (motilin)). In conclusion, motilin enhances contractions induced by electrical field stimulation in the rabbit antrum by a post-ganglionic interaction with the cholinergic neurotransmission in vitro at low doses and interacts directly with antral smooth muscle at high doses. This model is an accurate reflection of the in vivo effects of motilin and provides a tool to study neurogenic and myogenic actions of motilin and motilides in vitro. (C) 1997 Elsevier Science B.V