COVID-19 is an infection induced by the SARS-CoV-2 coronavirus, and severe forms can lead to acute respiratory distress syndrome (ARDS) requiring intensive care unit (ICU) management. Severe forms are associated with coagulation changes, mainly characterized by an increase in D-dimer and fibrinogen levels, with a higher risk of thrombosis, particularly pulmonary embolism. The impact of obesity in severe COVID-19 has also been highlighted.In this context, standard doses of low molecular weight heparin (LMWH) may be inadequate in ICU patients, with obesity, major inflammation, and hypercoagulability. We therefore urgently developed proposals on the prevention of thromboembolism and monitoring of hemostasis in hospitalized patients with COVID-19.Four levels of thromboembolic risk were defined according to the severity of COVID-19 reflected by oxygen requirement and treatment, the body mass index, and other risk factors. Monitoring of hemostasis (including fibrinogen and D-dimer levels) every 48 h is proposed. Standard doses of LMWH (e.g., enoxaparin 4000 IU/24 h SC) are proposed in case of intermediate thrombotic risk (BMI < 30 kg/m2, no other risk factors and no ARDS). In all obese patients (high thrombotic risk), adjusted prophylaxis with intermediate doses of LMWH (e.g., enoxaparin 4000 IU/12 h SC or 6000 IU/12 h SC if weight > 120 kg), or unfractionated heparin (UFH) if renal insufficiency (200 IU/kg/24 h, IV), is proposed. The thrombotic risk was defined as very high in obese patients with ARDS and added risk factors for thromboembolism, and also in case of extracorporeal membrane oxygenation (ECMO), unexplained catheter thrombosis, dialysis filter thrombosis, or marked inflammatory syndrome and/or hypercoagulability (e.g., fibrinogen > 8 g/l and/or D-dimers > 3 μg/ml). In ICU patients, it is sometimes difficult to confirm a diagnosis of thrombosis, and curative anticoagulant treatment may also be discussed on a probabilistic basis. In all these situations, therapeutic doses of LMWH, or UFH in case of renal insufficiency with monitoring of anti-Xa activity, are proposed.In conclusion, intensification of heparin treatment should be considered in the context of COVID-19 on the basis of clinical and biological criteria of severity, especially in severely ill ventilated patients, for whom the diagnosis of pulmonary embolism cannot be easily confirmed.

ROTEM is useful for the global assessment of coagulation in the operating theatre. EXTEM was the most informative for assessing the whole coagulation process and A10 showed value in guiding Plt and Fg transfusion.

Infection by SARS-CoV-2 is associated with a high risk of thrombosis. The laboratory documentation of hypercoagulability and impaired fibrinolysis remains a challenge. Our aim was to assess the potential usefulness of viscoelastometric testing (VET) to predict thrombotic events in COVID-19 patients according to the literature. We also (i) analyzed the impact of anticoagulation and the methods used to neutralize heparin, (ii) analyzed whether maximal clot mechanical strength brings more information than Clauss fibrinogen, and (iii) critically scrutinized the diagnosis of hypofibrinolysis. We performed a systematic search in PubMed and Scopus databases until December 31st, 2020. VET methods and parameters, and patients’ features and outcomes were extracted. VET was performed for 1063 patients (893 intensive care unit (ICU) and 170 non-ICU, 44 studies). There was extensive heterogeneity concerning study design, VET device used (ROTEM, TEG, Quantra and ClotPro) and reagents (with non-systematic use of heparin neutralization), timing of assay, and definition of hypercoagulable state. Notably, only 4 out of 25 studies using ROTEM reported data with heparinase (HEPTEM). The common findings were increased clot mechanical strength mainly due to excessive fibrinogen component and impaired to absent fibrinolysis, more conspicuous in the presence of an added plasminogen activator. Only 4 studies out of the 16 that addressed the point found an association of VETs with thrombotic events. So-called functional fibrinogen assessed by VETs showed a variable correlation with Clauss fibrinogen. Abnormal VET pattern, often evidenced despite standard prophylactic anticoagulation, tended to normalize after increased dosing. VET studies reported heterogeneity, and small sample sizes do not support an association between the poorly defined prothrombotic phenotype of COVID-19 and thrombotic events.

Introduction: Emicizumab (Hemlibra ® ) recently became available and requires an adaptation for managing bleeding, suspected bleeding and emergency or scheduled invasive procedures in haemophilia A patients with inhibitor. This implicates a multidisciplinary approach and redaction of recommendations for care that must be regularly adapted to the available data. Aim:The following text aims to provide a guide for the management of people with haemophilia A with inhibitor treated with emicizumab in case of bleeding or invasives procedures.

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Orthotopic liver transplantation (OLT) remains a potentially hemorrhagic procedure. Rotational thromboelastometry (ROTEM) is a point-of-care device used to monitor coagulation during OLT. Whether it allows blood loss and transfusions to be reduced during OLT remains controversial. Excellent correlations and predictive values have been found between ROTEM parameters and fibrinogen. We hypothesized that the use of a ROTEM-based transfusion algorithm during OLT would lead to more fibrinogen transfusion and decreased bleeding and blood transfusion. Sixty adult patients were consecutively included in a prospective, without-versus-with study: 30 in the group without ROTEM results and 30 in the group with the ROTEM-based algorithm. A small and nonsignificant increase in median fibrinogen transfusions was found for the with group (6.0 g versus 4.5 g, P 5 0.50). It was not associated with a decrease in blood transfusions or in the number of patients exposed to blood products. Liver Transpl 21:169-179, 2015. V C 2014 AASLD.Received June 26, 2014; accepted October 12, 2014.Orthotopic liver transplantation (OLT) remains a surgical procedure associated with major bleeding despite recent advances in the understanding and management of coagulation defects.1-3 Rotational thromboelastometry (ROTEM) is a point-of-care device used to monitor coagulation during cardiac surgery, for trauma patient care, and during OLT. 4,5 Good correlations have been found between ROTEM and laboratory results in the setting of OLT, 6,7 and transfusion algorithms have been implemented by anesthesia teams. However, ROTEM's ability to reduce blood loss and transfusions during OLT remains controversial. 8,9 ROTEM use is recommended by the European Society of Anaesthesiology.10 After a first study in which we gained experience and evaluated correlations between ROTEM parameters and standard laboratory tests, 6 we conducted a prospective, comparative withoutversus-with study to evaluate the impact of a ROTEM-based transfusion algorithm on transfusions and bleeding during OLT. We also performed laboratory blood analyses to manage blood cell counts and Abbreviations: A10, clot amplitude at 10 minutes; aPTT, activated partial thromboplastin time; AUC, area under the curve; ELT, euglobulin lysis time; FFP, fresh frozen plasma; ICU, intensive care unit; NPV, negative predictive value; OLT, orthotopic liver transplantation; PPV, positive predictive value; RBC, red blood cell; ROC, receiver operating characteristic; ROTEM, rotational thromboelastometry; TEG, thromboelastography.St ephanie Roullet and François Sztark have received honoraria from LFB Biom edicaments for lectures.LFB Biom edicaments and Tem-International financed the leasing of the rotational thromboelastometry device and provided the rotational thromboelastometry reagents.Address reprint requests to St ephanie Roullet, M.D., Service d'Anesth esie R eanimation 1

and the French Working Group on Perioperative Hemostasis * BACKGROUND: Because of the high risk of thrombotic complications (TCs) during SARS-CoV-2 infection, several scientific societies have proposed to increase the dose of preventive anticoagulation, although arguments in favor of this strategy are inconsistent.RESEARCH QUESTION: What is the incidence of TC in critically ill patients with COVID-19 and what is the relationship between the dose of anticoagulant therapy and the incidence of TC?STUDY DESIGN AND METHODS: All consecutive patients referred to eight French ICUs for COVID-19 were included in this observational study. Clinical and laboratory data were collected from ICU admission to day 14, including anticoagulation status and thrombotic and hemorrhagic events. The effect of high-dose prophylactic anticoagulation (either at intermediate or equivalent to therapeutic dose), defined using a standardized protocol of classification, was assessed using a time-varying exposure model using inverse probability of treatment weight.RESULTS: Of 538 patients included, 104 patients experienced a total of 122 TCs with an incidence of 22.7% (95% CI, 19.2%-26.3%). Pulmonary embolism accounted for 52% of the recorded TCs. Highdose prophylactic anticoagulation was associated with a significant reduced risk of TC (hazard ratio, 0.81; 95% CI, 0.66-0.99) without increasing the risk of bleeding (HR, 1.11; 95% CI, 0.70-1.75).INTERPRETATION: High-dose prophylactic anticoagulation is associated with a reduction in thrombotic complications in critically ill COVID-19 patients without an increased risk of hemorrhage. Randomized controlled trials comparing prophylaxis with higher doses of anticoagulants are needed to confirm these results.

Since 2011, data on patients exposed to direct oral anticoagulants (DOAs) while undergoing invasive procedures have accumulated. At the same time, an increased hemorrhagic risk during perioperative bridging anticoagulation without thrombotic risk reduction has been demonstrated. This has led the GIHP to update their guidelines published in 2011. For scheduled procedures at low bleeding risk, it is suggested that patients interrupt DOAs the night before irrespective of type of drug and to resume therapy six hours or more after the end of the invasive procedure. For invasive procedures at high bleeding risk, it is suggested to interrupt rivaroxaban, apixaban and edoxaban three days before. Dabigatran should be interrupted according to the renal function, four days and five days if creatinine clearance is higher than 50mL/min and between 30 and 50mL/min, respectively. For invasive procedures at very high bleeding risk such as intracranial neurosurgery or neuraxial anesthesia, longer interruption times are suggested. Finally, bridging with parenteral anticoagulation and measurement of DOA concentrations can no longer routinely be used.