Rivaroxaban or Placebo for Extended Antithrombotic Prophylaxis after Laparoscopic Surgery for Colorectal Cancer. the PRO-LAPS II Study

Background The clinical benefit of extending prophylaxis for venous thromboembolism (VTE) beyond hospital discharge after laparoscopic surgery for cancer is unclear. The efficacy and safety of thromboprophylaxis with direct oral anticoagulants in cancer surgery is unexplored. Methods PROLAPS II is an investigator-initiated, prospective, randomized, double-blind study aimed at assessing the efficacy and safety of extended prophylaxis with rivaroxaban compared with placebo after laparoscopic surgery for colorectal cancer (NCT03055026). All patients received antithrombotic prophylaxis with low molecular-weight heparin for 7±2 days and were then randomized to receive rivaroxaban (10 mg once daily) or placebo for the following 3 weeks (up to day 28±2 from surgery). The primary study outcome was the composite of symptomatic objectively confirmed VTE, asymptomatic ultrasonography-detected deep vein thrombosis (DVT) or VTE-related death within 28±2 days from laparoscopic surgery. The primary safety outcome was ISTH-defined major bleeding. By assuming an 8% incidence of primary study outcome in patients randomized to placebo and a 60% reduction with rivaroxaban, 323 patients per group were necessary to show the superiority of rivaroxaban. Results. Patient recruitment in PROLAPS II study was preliminary closed in June 7 th, 2021 due to study drug expiry, after the inclusion of 577 patients. The main patients features are reported in the Table. Study results will be available after the last study patient will complete the 90-day follow-up (scheduled on September 7th, 2021) and will be ready to be presented at the ASH 2021 Congress. Conclusion PROLAPS II is the first study with an oral anti-Xa agent in cancer surgery. The study has the potential to improve clinical practice by assessing the clinical benefit of extending prophylaxis after laparoscopic surgery for colorectal cancer. Figure 1 Figure 1. Disclosures Becattini: Bayer HealthCare: Honoraria; Daiichi Sankyo: Honoraria; Bristol Myers Squibb: Honoraria. Dentali: Pfizer: Honoraria; Bristol-Myers Squibb: Honoraria; Daiichi Sankyo: Honoraria; Bayer: Honoraria; Sanofi: Honoraria; Novartis: Honoraria; Boehringer: Honoraria; Alfa Sigma: Honoraria. Agnelli: Bayer HealthCare: Honoraria; Daiichi Sankyo: Honoraria; Pfizer: Honoraria; Bristol Myers Squibb: Honoraria.

COVID-19 with essential thrombocythemia treated with apixaban for antithrombotic prophylaxis

A 40-year-old man was admitted to our hospital for COVID-19. He had been treated for essential thrombocythemia (ET). He was diagnosed severe illness of COVID-19, oxygen therapy and dexamethasone were administered. There was a possibility of thromboembolic events in this case, apixaban for prophylaxis was added. With these treatments, the patient has made a good recovery, and he was discharged on hospital day 11. There is no standard strategy for prophylaxis of thrombosis in patients with ET, and apixaban could be a clinical benefit for these patients.

Thromboembolic events and antithrombotic prophylaxis in advanced ovarian cancer patients treated with bevacizumab: secondary analysis of the phase IV MITO-16A/MaNGO-OV2A trial

IntroductionThe use of routine antithrombotic prophylaxis is not recommended for advanced cancer patients receiving chemotherapy. The effect of bevacizumab-containing therapy on the risk of thromboembolic events remains controversial in ovarian cancer patients. We report on the incidence of thromboembolic events and the prevalence of antithrombotic therapy in patients enrolled in the single arm, phase IV, MITO-16A/MaNGO-OV2A trial.MethodsIn this trial, potential prognostic factors for patients with previously untreated ovarian cancer receiving a combination of platinum-based chemotherapy and bevacizumab were explored and the final analysis has already been reported. In this secondary analysis, the occurrence of thromboembolic events and the use of antithrombotic therapy were described according to the clinical characteristics of the patients. The prognostic role of thromboembolic events for progression-free and overall survival were also evaluated.ResultsFrom October 2012 to November 2014, 398 eligible patients were enrolled. 76 patients (19.1%) were receiving some type of anticoagulant or anti-aggregant treatment at baseline. Overall, 24 thromboembolic events were reported (cumulative incidence of 6.0%). The occurrence of thromboembolic events was not associated with baseline patient characteristics and was not modified by the use of antithrombotic prophylaxis (HR 0.60, 95% CI 0.18 to 2.0). Occurrence of thromboembolic events was not associated with progression-free survival (HR 1.34, 95% CI 0.83 to 2.15) or overall survival (HR 0.78, 95% CI 0.37 to 1.61).ConclusionsIn our study, a 6.0% rate of thromboembolic events was reported during treatment with bevacizumab plus chemotherapy. Thromboembolic events were not associated with the clinical characteristics of the patients or with the use of antithrombotic prophylaxis, nor did they significantly affect the long-term prognosis.Trial registration numberNCT01706120

Effectiveness of antithrombotic prophylaxis in paediatric cardiosurgical patients

<p><strong>Aim.</strong> To evaluate the effectiveness of prevention measures for thrombotic catheter-associated events in the perioperative management of patients undergoing cardiac surgery.</p><p><strong>Methods.</strong> A total of 433 paediatric and neonatal patients were included in the study during the period from January to December 2018. All patients received antithrombotic prophylaxis via systemic heparin administration.</p><p><strong>Results.</strong> Thirty-six patients displayed signs of thrombosis during the postoperative period (8.31%): 28 patients had venous thrombosis, while 6 had the Blalock-Taussig shunt thrombosis, and 2 had arterial thrombosis. The mortality rate was higher in the group with registered thrombosis than in the group without thrombosis (p = 0.01).</p><p><strong>Conclusion.</strong> The dosage regimen for children and neonatal patients should be according to age-associated antithrombotic drug standards. It requires an integral approach for evaluating the effectiveness of preventive and therapeutic measures.</p><p>Received 25 August 2020. Revised 18 December 2020. Accepted 22 December 2020.</p><p><strong>Funding:</strong> The study did not have sponsorship.</p><p><strong>Conflict of interest:</strong> Author declares no conflict of interest.</p>

Characteristics and treatment of coagulopathy associated with COVID-19

Coagulopathy in COVID-19 represents a thrombo-inflammatory condition, and it is one of the most important causes of morbidity and mortality in this disease. The occurrence of coagulopathy correlates with the intensity of the inflammatory response to SARS-Cov-2 virus infection, and its presence is characterized by laboratory markers of blood hypercoagulability and clinically pronounced prothrombotic condition. Although the mechanism of coagulopathy is not fully elucidated, dysregulated and overemphasized immune responses mediated by inflammatory cytokines, complement activation, leukocyte activation with release of free nucleic acids and histones into the circulation, hypoxia and endothelial damage play a very important role in its development. Thrombosis can occur in all parts of the circulatory system and is most often localized in the microcirculation and venous part of the vasculature. A number of studies have shown that the presence of thrombotic pulmonary embolism can be demonstrated by objective methods in approximately 15% of COVID-19 patients treated in intensive care units, while the incidence of total venous thromboembolism in this group of patients is over 20% despite antithrombotic prophylaxis. Although much less common than venous thrombosis, arterial thrombosis may also occur in COVID-19 patients, most often in the form of myocardial infarction, ischemic stroke and peripheral artery occlusion. Damage to the endothelium under the influence of virus or inflammatory response, activation of platelets and coagulation system with fibrin deposition leads to extensive thrombosis in the microcirculation of lungs and other tissues and directly contributes to respiratory failure, ARDS or multiorgan failure. Therefore, coagulopathy in COVID-19 is an integral part of the pathophysiological mechanism of the disease and contributes to its clinical manifestation and progression. Main laboratory characteristics of COVID-19 coagulopathy are elevated values of D-dimer in the blood, which occurs in the process of decomposition of precipitated fibrin under the action of fibrinolytic enzymes in the microcirculation of the lungs and other organs. Therefore, D-dimer values reflect the intensity of the inflammation in the lungs and have prognostic significance in recognizing patients at risk of serious complications and unfavorable course of the disease. In contrast to disseminated intravascular coagulation in sepsis, severe thrombocytopenia and hypofibrinogenemia as well as bleeding tendencies are rare in COVID-19 coagulopathy. Due to the high frequency and important role of coagulopathy in morbidity and mortality, the use of anticoagulant therapy is recommended in all hospitalized patients. However, the optimal way of treating coagulopathy and the intensity of antithrombotic prophylaxis are not known, and represent the subject of intensive research.