The role of anticoagulation clinics needs to be reassessed to include follow up of patients on direct oral anticoagulants.

A survey was carried out to assess the state of organization of care (including clinical and laboratory) delivered to patients on vitamin K antagonists (VKA) or direct oral anticoagulants (DOAC) followed by clinics affiliated with the Italian Federation of Thrombosis Centers (FCSA), traditionally engaged to assist anticoagulated outpatients within the country. Participants were asked to answer questions concerning (i) proportion of patients on VKA-vs-DOAC and (ii) whether dedicated testing for DOAC is available. The proportion of patients on VKA-vs-DOAC was 60 % vs 40 %.

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.

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.

Anti-TNF-α Treatment Reduces the Baseline Procoagulant Imbalance of Patients With Inflammatory Bowel Diseases.

Background: Inflammatory bowel diseases (IBD) are characterized by an increased thrombosis risk of uncertain etiology. Coagulation derangement arising from inflammation may be a triggering factor. We hypothesized that strong inflammation inhibitors (eg, anti-tumor necrosis factor-α drugs) may affect coagulation.

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.

Hypercoagulability of COVID-19 patients in intensive care unit: A report of thromboelastography findings and other parameters of hemostasis.

Background: The severe inflammatory state secondary to COVID-19 leads to a severe derangement of hemostasis that has been recently described as a state of disseminated intravascular coagulation (DIC) and consumption coagulopathy, defined as decreased platelet count, increased fibrin(ogen) degradation products such as D-dimer, as well as low fibrinogen.

Aims: Whole blood from 24 patients admitted at the intensive care unit because of COVID-19 was collected and evaluated with thromboelastography by the TEG point-of-care device on a single occasion and six underwent repeated measurements on two consecutive days for a total of 30 observations. Plasma was evaluated for the other parameters of hemostasis.

Effect of different methods for outlier detection and rejection when calculating cut off values for diagnosis of lupus anticoagulants.

Background: Lupus anticoagulant (LA)-detection is performed by testing plasma with activated partial thromboplastin time (APTT)-derived and dilute-Russell-viper-venom (dRVV)-derived tests. Results are interpreted by comparison to cut-off values determined by testing plasma from healthy-subjects. Several issues are concerned with the determination of LA cut-offs.

Procoagulant imbalance in preterm neonates detected by thrombin generation procedures.

Preterm newborns are considered at risk of acquired coagulopathy and are often prophylactically infused with fresh frozen plasma (FFP) even in the absence of bleeding. To assess the coagulation asset of preterm neonates and the biological plausibility of such infusions, we investigated at birth 87 very low birth weight (≤1500 g) preterm (gestational age <35 weeks) newborns and 64 full-term newborns. Preterm neonates were also investigated at different time-points up to 30 days after birth.

Effect of emicizumab on global coagulation assays for plasma supplemented with apixaban or argatroban.

Emicizumab is a bi-specific humanized monoclonal antibody mimicking the factor (F) VIII cofactor activity in mediating the activation of FX by FIXa. Recent observations showed that emicizumab when added to pooled normal plasma (PNP), hemophilic plasma or PNP added with unfractionated heparin is able to interfere with coagulation assays. To further explore the mechanisms of assay interference we investigated the effect of emicizumab on global coagulation assays for the PNP added with two direct oral anticoagulants, apixaban or argatroban.

Procoagulant imbalance influences cardiovascular and liver damage in chronic hepatitis C independently of steatosis.

Background & Aims: Patients with chronic HCV infection besides hepatitis often present cardiovascular damage, the pathogenesis of which is not defined. In chronic liver diseases, including NAFLD and cirrhosis, a procoagulant imbalance, potentially responsible for atherosclerosis has been reported. We aimed at evaluating whether a procoagulant imbalance is present also in non-cirrhotic patients with HCV infection and whether the procoagulant imbalance correlates with cardiovascular damage.

Body mass index reduction improves the baseline procoagulant imbalance of obese subjects.

Obesity is a risk factor for cardiovascular diseases. The latter being dependent (at least in part) on plasma procoagulant imbalance (i.e.

The intra-assay reproducibility of thromboelastography in very low birth weight infants.

Background And Aims: Despite the potential benefits of thromboelastography (TEG) for bedside hemostatic assessment in critical care settings, its accuracy remains to be determined, especially in critically ill neonates. We determined the intra-assay reproducibility of TEG parameters: Reaction time (R), clot kinetics (K) and Maximum Amplitude (MA) in a cohort of very low birth weight (VLBW) infants.

Study Design: Observational study.

Advances in the Treatment of Hemophilia: Implications for Laboratory Testing.

Background: Until recently, clinical laboratories have monitored hemophilia treatment by measuring coagulation factors before/after infusion of human-derived or recombinant factors. Substantial changes are expected in the near future based on new therapeutic approaches that have been or are being developed.

Content: Hemophilia treatment includes replacement therapy with human-derived/recombinant factors or treatment with bypassing agents for patients without or with inhibitors, respectively.

Interlaboratory variability in the measurement of direct oral anticoagulants: results from the external quality assessment scheme.

Unlabelled: Essentials Tests for direct oral anticoagulants (DOACs) are not widely applied. These tests are perceived to be difficult to run and subjected to large between-lab variation. We carried out proficiency testing surveys for DOAC testing in Italy.

International collaborative study for the calibration of proposed International Standards for thromboplastin, rabbit, plain, and for thromboplastin, recombinant, human, plain.

Unlabelled: Essentials Two candidate International Standards for thromboplastin (coded RBT/16 and rTF/16) are proposed. International Sensitivity Index (ISI) of proposed standards was assessed in a 20-centre study. The mean ISI for RBT/16 was 1.

Lupus Anticoagulant Testing: Activated Partial Thromboplastin Time (APTT) and Silica Clotting Time (SCT).

Actvated partial thromboplastin time and its congener test Silica clotting time are used for the laboratory detection of lupus anticoagulants. Their performance consists of mixing test plasma with activators of the contact coagulation factors, phospholipids and calcium chloride, and recording the clotting time. Here we describe the principle, performance and extensive practical details of the two methods, the problems that may be encountered and how they can be identified and overcome.

Variability of cut-off values for the detection of lupus anticoagulants: results of an international multicenter multiplatform study.

Unlabelled: Essentials Between-lab variations of cut-off values in lupus anticoagulant detection are unknown. Cut-off values were calculated in 11 labs each testing plasma from 120 donors with 3 platforms. Major variation was observed even within the same platform.

Evaluation of coagulation during treatment with directly acting antivirals in patients with hepatitis C virus related cirrhosis.

Background & Aims: The effect of direct-acting-antivirals (DAA) on coagulation of hepatitis-C-virus (HCV)-related cirrhosis is unknown.

Methods: We investigated 28 patients on DAA treatment and performed prothrombin-time, thrombin generation with and without thrombomodulin, whole-blood thromboelastometry, as well as the individual procoagulants (II, VIII, XIII, von Willebrand) and anticoagulants, antithrombin and protein-C.

Results: Patients had undetectable HCV-RNA at the end-of- treatment and at 12-weeks after end-of-treatment (sustained virological response).