Clot characterization by multidisciplinary approach: biochemical and imaging parameters in a hypocoagulative setting. A pilot study.

Background: Clot characterization is, to the present days, a multimodal approach: scanning the clot by electron microscopy (SEM) is helpful for the visualization of fibrin structure along with laboratory parameters such as the clot waveform analysis (CWA) and thrombin generation in different settings of clot abnormalities. This study aimed to assess whether the coagulative parameters were consistent with the clot images texture acquired by SEM, and therefore to propose a more generalist and integrative approach to clots classification.Design and Methods: In this pilot study, the examined population consists of eight healthy subjects, seven patients affected by Acquired Hemophilia A (AHA) and seven patients treated with Vitamin K Antagonists (VKAs), similar for age and gender. We studied the velocity and acceleration (1st and 2nd derivative of the aPTT) of clot formation (CWA), the thrombin generation, and the clots' scanning by SEM. Images acquired with SEM were then analyzed with the MATLAB software with the "Texture Analysis" methods to perform classification. Among the various texture parameters, we reported Contrast and Energy.Results: Significant differences among healthy subjects, patients with AHA and those treated with VKAs were detected for the coagulative parameters. We found no differences between VKAs and AHA patients. Contrast and energy highlighted a significant difference among the three groups in agreement with the laboratory's parameters. We found no significant differences between VKAs and AHA patients.Conclusions: The use of SEM, CWA and thrombin generation parameters may be a starting point for studies aimed to demonstrate the general characteristics of clot formation in different clinical conditions with a multiparametric approach

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Points of Care Testing International Normalized Ratio: Are They Useful for Monitoring Vitamin K Antagonists in a Thrombosis Center?

Point of care testing (POCT) international normalized ratio (INR) devices are widely accepted for self-testing and self-management of vitamin K antagonists (VKAs). The aim of this work was to evaluate the performance of a POCT at our thrombosis centre aiming at reducing the time spent by patients for blood sampling and dose adjustment. A total of 101 consecutive oral anticoagulated patients (53 M, 48 F, median age 74 years, 23-89) were enrolled in the study that consisted of 2 different phases. In the first, standard monitoring was carried out for 3 months; during this period, the INR value was also determined by capillary blood sample with the use of a POCT to compare the INR values obtained with the two systems. In the second phase, patients were monitored for 3 months using only the CoaguChek XS Plus. The Bland-Altman test showed a good agreement between INR values obtained with the automated coagulometer and the CoaguChek XS Plus. The Passing and Bablok test showed no significant deviation from linearity. The total median waiting time was 3 hours and 45 minutes (from 0:44 to 6:05) and 1 hour and 16 minutes (P < 0.001) during standard monitoring and the use of the CoaguChek XS Plus, respectively. CoaguChek XS Plus is a suitable POCT for monitoring VKA therapy at a thrombosis centre, thus significantly reducing the time spent by patients for blood sampling and waiting for dosage adjustment

Point-of-care testing INR: an overview

Abstract Oral anticoagulant therapies with the anti-vitamin K drugs (AVK), warfarin, acenocoumarol and phenprocoumon, are employed in primary and secondary anti-thrombotic prophylaxis in patients with venous thromboembolism, atrial fibrillation and cardiac mechanical valves. However, a monitoring test such as the International Normalized Ratio (INR) is required. The periodic monitoring of this therapy entails discomfort for the patients. Telemedicine and telecare can provide significant aid in the management of this therapy allowing patients to perform the test at home or anywhere else with a portable device, i.e. point-of-care testing (POCT), and to send the result to a thrombosis (TC) via web. Patients can receive dose adjustment sent back by the TC. The effectiveness of this type of management is equal or superior to the traditional AVK monitoring in terms of hemorrhagic and thrombotic events. Analysis of the costs with a horizon of 10 years reveals that both self-testing and self-management are cost-effective. The aim of this overview is to describe the pros and cons of the use of POCT as an alternative in the monitoring of AVK. In particular, description of the POCT, decentralization, quality of the therapy, safety and costs will be examined.</jats:p

Hyperhomocysteinemia: could the post-methionine oral loading test sometimes be avoided?

Background and Objectives. Measurement of homocysteinemia, a risk factor for venous and arterial thrombosis, is carried out in patients fasting for 12 hours and after an oral methionine load (PML). The procedure is time-consuming and several of the patients suffer from nausea and malaise. We wondered whether methionine loading could sometimes be avoided by considering fasting homocysteinemia (tHcy) levels. Design and Methods. We evaluated whether fasting tHcy levels were useful to predict PML and ΔPML tHcy with acceptable sensitivity and specificity in 381 patients with venous and arterial thrombosis through the generation of receiver operating characteristic curves. Results. Both PML and ΔPML tHcy correlated with fasting tHcy values. The cut-off of fasting tHcy value yielding a 100% sensitivity in predicting normal PML and ΔPML tHcy was 6.5 and 5.0 μmol/L in females, and 7.1 and 7.2 μmol/L in males. Fasting tHcy values yielding a 95% specificity in predicting a positive PML and tHcy result ranged from 12.5 to 13.1 μmol/L in males and from 10.4 to 10.5 μmol/L in females. A 95% specificity in predicting a positive ΔPML tHcy result ranged from 10.8 to 11.6 μmol/L in females and from 15.9 to 17.0 μmol/L in men. Considering PML tHcy, 186 out of 381 patients could have avoided methionine loading while using ΔPML tHcy 123 out of 381 could have done so. Interpretation and Conclusions. Nearly 50% of our patients considering PML tHcy, and about 30% considering δPML tHcy could have been spared the methionine loading test. We propose this model for those who wish to carry out this analysis on their own