Comparative Investigation of Thromboelastometry and Thrombin Generation for Patients Receiving Direct Oral Anticoagulants or Vitamin K Antagonists.

. Alterations induced by direct oral anticoagulants (DOACs) or vitamin K antagonists (VKAs) to thromboelastometry and thrombin generation are not well defined. We performed a simultaneous investigation of thromboelastometry and thrombin generation for patients who were chronically anticoagulated with DOACs or VKAs.

Predictive parameters for spontaneous joint bleeding during emicizumab prophylaxis.

Emicizumab is approved for prophylaxis of patients with hemophilia A (HA). Despite its efficacy in reducing bleeding, some patients on emicizumab still experience hemarthrosis, but no tool is yet available to identify those at a higher risk of spontaneous joint bleeding. This study aimed to evaluate whether laboratory measurements (global coagulation assays and emicizumab concentration) and/or arthropathy scores can distinguish patients at higher risk of spontaneous joint bleeding while on emicizumab prophylaxis.

How the Hemostasis Laboratory Can Help Clinicians to Manage Patients on Oral Anticoagulants.

Oral anticoagulants are widely used to treat or prevent cardiovascular diseases in millions of patients worldwide. They are the drugs of choice for stroke prevention and systemic embolism in patients with non-valvular atrial fibrillation and prosthetic heart valves, as well as for treatment/prevention of venous thromboembolism. Oral anticoagulants include vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs).

Defining a metrologically traceable and sustainable calibration hierarchy of international normalized ratio for monitoring of vitamin K antagonist treatment in accordance with International Organization for Standardization (ISO) 17511:2020 standard: communication from the International Federation of Clinical Chemistry and Laboratory Medicine-SSC/ISTH working group on prothrombin time/international normalized ratio standardization.

Calibration of prothrombin time (PT) in terms of international normalized ratio (INR) has been outlined in "Guidelines for thromboplastins and plasmas used to control oral anticoagulant therapy" (World Health Organization, 2013). The international standard ISO 17511:2020 presents requirements for manufacturers of in vitro diagnostic (IVD) medical devices (MDs) for documenting the calibration hierarchy for a measured quantity in human samples using a specified IVD MD. The objective of this article is to define an unequivocal, metrologically traceable calibration hierarchy for the INR measured in plasma as well as in whole blood samples.

Laboratory Diagnosis of Antiphospholipid Syndrome in Anticoagulated Patients.

The laboratory diagnosis of antiphospholipid syndrome (APS) requires the measurement of solid-phase antibodies to cardiolipin or β2-Glycoprotein-I and the search for lupus anticoagulant (LA). The diagnosis of patients whilst on anticoagulation is impaired by the difficult interpretation of results, at least for LA, owing to the fact that prolongations of clotting times induced by LA superimpose those induced by anticoagulants. This is a matter of concern as treating physicians very often need to know the APS status of their patients to make a decision on secondary antithrombotic prophylaxis.

Thromboplastin calibration revisited to look for possible revision of the World Health Organization recommendations.

Background: Thromboplastin calibration is essential to determine the international sensitivity index required to calculate the international normalized ratio (INR). The procedure for calibration recommended by the World Health Organization (WHO) calls for the selection of patients on stable anticoagulation in the range of 1.5 to 4.

Clinical and genetic determinants of the fatty liver-coagulation balance interplay in individuals with metabolic dysfunction.

Background & Aims: The aim of this study was to examine the determinants of the interplay between liver damage and the coagulation balance in individuals at risk of non-alcoholic fatty liver disease (NAFLD).

Methods: We considered 581 healthy participants with ≥3 metabolic alterations undergoing clinical and genomic evaluation, measurement of liver stiffness (LSM) and controlled attenuation parameter (CAP) by Fibroscan, Pro-C3, coagulation balance (von Willebrand factor [vWF], factor VIII/protein C ratio [F8/PC] as the main outcome, D-dimer as marker of coagulation/fibrinolysis activation).

Results: Liver fibrosis indices (both Fibrosis-4 [FIB-4] and liver stiffness measurement [LSM]), but not liver fat (CAP), were independently associated with higher F8/PC ratio ( <0.

No changes of parameters nor coagulation activation in healthy subjects vaccinated for SARS-Cov-2.

Background: Recent reports of thrombotic events after SARS-Cov-2 vaccination raised concern. However, modifications of the most common coagulation parameters after vaccination are unknown.

Aims: We measured parameters of coagulation including (i) basic coagulation tests, (ii) procedures aimed to assess the ex-vivo potential capacity to generate thrombin and (iii) in vivo thrombin activity.

Pro-coagulant imbalance in patients with community acquired pneumonia assessed on admission and one month after hospital discharge.

Objectives: Patients hospitalized because of community-acquired-pneumonia (CAP) are at risk of cardiovascular diseases. Although plasma procoagulant imbalance play a role, mechanisms are not completely understood. We aimed to investigate whether there is a measurable state of procoagulant imbalance following inflammation determined by CAP.

Impact of a commercially available DOAC absorbent on two integrated procedures for lupus anticoagulant detection.

Background: Lupus anticoagulant (LA)-detection in anticoagulated patients is an unmet need, which becomes even more cogent with the introduction of direct oral anticoagulants (DOAC) that may lead to false-positive results.

Aims: We aimed to investigate the effect of a commercially available DOAC absorbent on residual drug concentrations, and on integrated procedures for LA-detection.

Methods: Blood from patients treated for atrial fibrillation with either dabigatran (n = 39), rivaroxaban (n = 55), apixaban (n = 47) or edoxaban (n = 47) were collected at peak and trough, and centralized for testing with two LA integrated procedures [i.

Evaluation of procoagulant imbalance in Cushing's syndrome after short- and long-term remission of disease.

Objective: Patients with Cushing's syndrome (CS) are at high risk of venous thromboembolism related to a hypercoagulability due to procoagulant imbalance. However, whether these alterations are reversible after disease remission is still unclear. The endogenous thrombin potential (ETP) measured with and without the addition of thrombomodulin provides a global representation of coagulation and previous data confirmed hypercoagulable profile in patients with active hypercortisolism.

Plasma levels of extracellular vesicles and the risk of post-operative pulmonary embolism in patients with primary brain tumors: a prospective study.

Primary brain tumors are associated with an increased risk of pulmonary embolism (PE), particularly in the early post-operative period. The pathophysiological mechanisms of PE are poorly understood. This study aims to describe prospectively extracellular vesicles (EVs) levels and investigate whether or not their variations allow to identify patients at increased risk of post-operative PE.

Assessment of Platelet Thrombus Formation under Flow Conditions in Adult Patients with COVID-19: An Observational Study.

Background:  Coronavirus disease 2019 (COVID-19) is associated with systemic inflammation, which may dysregulate platelet function. Total Thrombus-Formation Analysis System (T-TAS) is a flow-chamber device that analyses platelet-mediated thrombus formation in capillary channels through the following parameters: (1) the area under the flow-pressure curve (AUC), (2) occlusion start time (OST), time needed to reach OST, and (3) occlusion time (OT), time needed to reach the occlusion pressure.

Methods And Findings:  Sixty-one COVID-19 patients admitted to intensive, subintensive, and low intensive care were prospectively enrolled according to the time of admission: group A (up to 8 days) ( = 18); group B (from 9 to 21 days) ( = 19), and group C ( > 21 days) ( = 24).

Procoagulant Imbalance in Klinefelter Syndrome Assessed by Thrombin Generation Assay and Whole-Blood Thromboelastometry.

Context: Klinefelter syndrome (KS) is a condition at increased risk of thrombosis compared to 46,XY men.

Objective: This work aimed to investigate the coagulation balance of KS patients by thrombin generation assay (TGA) and thromboelastometry.

Methods: An observational, cross-sectional study was conducted at 3 tertiary endocrinological centers in Milan, Italy.

Thrombin Generation in Preterm Newborns With Intestinal Failure-Associated Liver Disease.

Intestinal failure-associated liver disease (IFALD) affects one-fifth of neonates receiving parenteral nutrition (PN) for more than 2 weeks. We aimed to define the effect of IFALD on hemostasis of preterm infants. This is an ancillary analysis of a prospective study aimed at defining coagulation in preterm infants.

Emicizumab, the factor VIII mimetic bi-specific monoclonal antibody and its measurement in plasma.

Objectives: Emicizumab, a monoclonal antibody mimicking the function of factor (F) VIII in the activation of FX by FIXa, is widely used for prophylaxis in hemophilia patients with or without inhibitors to FVIII. Although it is administered at fixed dose, its measurement could be occasionally required. In principle, the emicizumab procoagulant effect could be assessed by the one-stage assay (OSA) currently used to measure FVIII.

Paving the way for establishing a reference measurement system for standardization of plasma prothrombin time: Harmonizing the manual tilt tube method.

Background: International normalized ratio (INR) is traceable to World Health Organization (WHO) International Standards for thromboplastins. International Standards must be used with a manual tilt tube technique (MTT) for prothrombin time (PT) determination. An important part of the total variability of INR is due to poor harmonization of MTT across WHO reference laboratories.