Effect of PCC on Thrombin Generation among Patients on Factor Xa Inhibitors with Major Bleeding or Needing Urgent Surgery (GAUGE): Design and Rationale.

Background Direct factor Xa inhibitors (FXaIs) account for most oral anticoagulant use and FXaI-associated bleeding events are common. Clinicians have variable national and regional access to specific FXaI reversal agents such as andexanet alfa. Many centers have adopted the use of prothrombin complex concentrates (PCCs) as hemostatic therapy for FXaI-associated major bleeding events. PCC does not impact circulating FXaI levels and its mechanism of action to achieve hemostasis in FXaI-associated bleeding is uncertain. While PCC increases quantitative thrombin generation assay (TGA) parameters, it does not correct FXaI-altered thrombin generation kinetics, nor does it normalize thrombin generation. Clinical data supporting the use of PCC are based on cohort studies reporting clinical hemostatic efficacy, which is difficult to measure. The benefits of PCC for FXaI-associated bleeding beyond supportive care are uncertain. Objective GAUGE is a prospective observational study designed to measure the effects of four-factor PCC administration (Octaplex) on TGA parameters among patients with FXaI-associated bleeding or needing urgent surgery. Methods Laboratory outcomes will include the mean paired change in TGA parameters from pre- to post-PCC administration and the proportion of participants whose post-PCC TGA values fall within a defined reference range. Clinical outcomes will include hemostatic efficacy, thromboembolic complications, and all-cause death at 30 days post-PCC. Conclusion Development of a viable and universally accessible FXaI bleed management strategy is crucial. GAUGE will provide in vivo data on the effects of PCC among patients with FXaI-associated bleeding.

Perioperative Coagulation Profile in Major Liver Resection for Cancer: A Prospective Observational Study.

Hepatectomy-induced coagulation disturbances have been well studied over the past decade. Cumulative evidence supports the superiority of global coagulation analysis compared with conventional coagulation tests (i.e., prothrombin time or activated partial thromboplastin time) for clinical decision making. Cancer, however, represents an acquired prothrombotic state and liver resection for cancer deserves a more thorough investigation. This prospective observational study was conducted to assess the perioperative coagulation status of patients undergoing major hepatectomies for primary or metastatic hepatic malignancy. Patients were followed up to the 10th post-operative day by serial measurements of conventional coagulation tests, plasma levels of coagulation factors, and thrombin generation assay parameters. An abnormal coagulation profile was detected at presentation and included elevated FVIII levels, decreased levels of antithrombin, and lag time prolongation in thrombin generation. Serial hematological data demonstrated increased Von Willebrand factor, FVIII, D-dimer, fibrinogen and decreased levels of natural anticoagulant proteins in the early post-operative period predisposing to a hyper-coagulable state. The ratio of the anticoagulant protein C to the procoagulant FVIII was low at baseline and further declined post-operatively, indicating a prothrombotic state. Though no bleeding complications were reported, one patient experienced pulmonary embolism while under thromboprophylaxis. Overall, patients with hepatic carcinoma presenting for elective major hepatectomy may have baseline malignancy-associated coagulation disturbances, aggravating the hyper-coagulable state documented in the early post-operative period.

The COVID-19 Pandemic and the Need for an Integrated and Equitable Approach: An International Expert Consensus Paper.

BACKGROUND: One year after the declaration of the coronavirus disease 2019 (COVID-19) pandemic by the World Health Organization (WHO) and despite the implementation of mandatory physical barriers and social distancing, humanity remains challenged by a long-lasting and devastating public health crisis. MANAGEMENT: Non-pharmacological interventions (NPIs) are efficient mitigation strategies. The success of these NPIs is dependent on the approval and commitment of the population. The launch of a mass vaccination program in many countries in late December 2020 with mRNA vaccines, adenovirus-based vaccines, and inactivated virus vaccines has generated hope for the end of the pandemic. CURRENT ISSUES: The continuous appearance of new pathogenic viral strains and the ability of vaccines to prevent infection and transmission raise important concerns as we try to achieve community immunity against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) and its variants. The need of a second and even third generation of vaccines has already been acknowledged by the WHO and governments. PERSPECTIVES: There is a critical and urgent need for a balanced and integrated strategy for the management of the COVID-19 outbreaks organized on three axes: (1) Prevention of the SARS-CoV-2 infection, (2) Detection and early diagnosis of patients at risk of disease worsening, and (3) Anticipation of medical care (PDA). CONCLUSION: The "PDA strategy" integrated into state policy for the support and expansion of health systems and introduction of digital organizations (i.e., telemedicine, e-Health, artificial intelligence, and machine-learning technology) is of major importance for the preservation of citizens' health and life world-wide.