Predictive value of coagulation variables and glycocalyx shedding in hospitalized COVID-19 patients - a prospective observational study.

OBJECTIVES: Covid-19 disease causes an immense burden on the healthcare system. It has not yet been finally clarified which patients will suffer from a severe course and which will not. Coagulation disorders can be detected in many of these patients. The aim of the present study was therefore to identify variables of the coagulation system including standard and viscoelastometric tests as well as components of glycocalyx damage that predict admission to the intensive care unit. METHODS: Adult patients were included within 24 h of admission. Blood samples were analyzed at hospital admission and at ICU admission if applicable. We analyzed group differences and furthermore performed receiver operator characteristics (ROC). RESULTS: This study included 60 adult COVID-19 patients. During their hospital stay, 14 patients required ICU treatment. Comparing ICU and non-ICU patients at time of hospital admission, D-dimer (1450 µg/ml (675/2850) vs. 600 µg/ml (500/900); p = 0.0022; cut-off 1050 µg/ml, sensitivity 71%, specificity 89%) and IL-6 (47.6 pg/ml (24.9/85.4 l) vs. 16.1 pg/ml (5.5/34.4); p = 0.0003; cut-off 21.25 pg/ml, sensitivity 86%, specificity 65%) as well as c-reactive protein (92 mg/dl (66.8/131.5) vs. 43.5 mg/dl (26.8/83.3); p = 0.0029; cutoff 54.5 mg/dl, sensitivity 86%, specificity 65%) were higher in patients who required ICU admission. Thromboelastometric variables and markers of glycocalyx damage (heparan sulfate, hyaluronic acid, syndecan-1) at the time of hospital admission did not differ between groups. CONCLUSION: General inflammatory variables continue to be the most robust predictors of a severe course of a COVID-19 infection. Viscoelastometric variables and markers of glycocalyx damage are significantly increased upon admission to the ICU without being predictors of ICU admission.

Modified thromboelastometric tests provide improved sensitivity and specificity to direct oral anticoagulants compared to standard thromboelastometric tests in-vitro.

BACKGROUND: The detection of direct oral anticoagulants (DOACs) is still challenging but important in emergency patients. We recently demonstrated that modified thromboelastometry can detect rivaroxaban and dabigatran. Data on the detection rates of modified compared to standard thromboelastometric tests of apixaban and edoxaban, are missing. The aim of this in-vitro dose-effect-study was to add data on these DOACs and to evaluate thromboelastometric tests in-vitro using data of both studies. METHODS: The study was approved by the Ludwig-Maximilians-University ethics committee (No 17-525-2). Written informed consent was obtained from all individuals. Blood samples of healthy volunteers and samples of 10 volunteers for each DOAC were used. Blood samples were spiked with six different concentrations of edoxaban and apixaban (0ng/ml; 31.25ng/ml; 62.5ng/ml; 125ng/ml; 250 ng/ml; 500ng/ml). Modified tests (low-tissue-factor test TFTEM and ecarin-based test ECATEM) as well as standard tests (e.g. FIBTEM) analyzing extrinsic pathway of coagulation were used. Receiver operating characteristics analyzes were performed as well as regression analyzes. RESULTS: TFTEM CT correlated well with anti-Xa levels of apixaban and edoxaban (apixaban: r2 = 0.8064 p < 0.0001; edoxaban: r2 = 0.8603; p < 0.0001). The detection of direct FXa inhibitors (> 30 ng/mL) was successful with FIBTEM CT with a sensitivity and specificity of 81% and 90%, respectively. As expected, ECATEM CT was not prolonged by direct FXa-inhibitors due to its specificity for direct thrombin inhibitors. Again, TFTEM CT provided the highest sensitivity and specificity for the detection of direct FXa inhibitors with 96% and 95%, respectively. ECATEM test showed 100% sensitivity and 100% specificity for the detection of dabigatran. CONCLUSIONS: Our study presents modified thromboelastometric tests with improved detection of even low DOAC concentrations > 30 ng/mL, including apixaban in-vitro. The study thus complements the previously published data on dabigatran and rivaroxaban. Validation studies must confirm the results due to the explanatory design of this study.

Sulforaphane Reduces Prostate Cancer Cell Growth and Proliferation In Vitro by Modulating the Cdk-Cyclin Axis and Expression of the CD44 Variants 4, 5, and 7.

Prostate cancer patients whose tumors develop resistance to conventional treatment often turn to natural, plant-derived products, one of which is sulforaphane (SFN). This study was designed to determine whether anti-tumor properties of SFN, identified in other tumor entities, are also evident in cultivated DU145 and PC3 prostate cancer cells. The cells were incubated with SFN (1-20 µM) and tumor cell growth and proliferative activity were evaluated. Having found a considerable anti-growth, anti-proliferative, and anti-clonogenic influence of SFN on both prostate cancer cell lines, further investigation into possible mechanisms of action were performed by evaluating the cell cycle phases and cell-cycle-regulating proteins. SFN induced a cell cycle arrest at the S- and G2/M-phase in both DU145 and PC3 cells. Elevation of histone H3 and H4 acetylation was also evident in both cell lines following SFN exposure. However, alterations occurring in the Cdk-cyclin axis, modification of the p19 and p27 proteins and changes in CD44v4, v5, and v7 expression because of SFN exposure differed in the two cell lines. SFN, therefore, does exert anti-tumor properties on these two prostate cancer cell lines by histone acetylation and altering the intracellular signaling cascade, but not through the same molecular mechanisms.