Convalescent or standard plasma versus standard of care in the treatment of COVID-19 patients with respiratory impairment: short and long-term effects. A three-arm randomized controlled clinical trial.

BACKGROUND: The efficacy of early treatment with convalescent plasma in patients with COVID-19 is debated. Nothing is known about the potential effect of other plasma components other than anti-SARS-CoV-2 antibodies. METHODS: To determine whether convalescent or standard plasma would improve outcomes for adults in early phase of Covid19 respiratory impairment we designed this randomized, three-arms, clinical trial (PLACO COVID) blinded on interventional arms that was conducted from June 2020 to August 2021. It was a multicentric trial at 19 Italian hospitals. We enrolled 180 hospitalized adult patients with COVID-19 pneumonia within 5 days from the onset of respiratory distress. Patients were randomly assigned in a 1:1:1 ratio to standard of care (n = 60) or standard of care + three units of standard plasma (n = 60) or standard of care + three units of high-titre convalescent plasma (n = 60) administered on days 1, 3, 5 after randomization. Primary outcome was 30-days mortality. Secondary outcomes were: incidence of mechanical ventilation or death at day 30, 6-month mortality, proportion of days with mechanical ventilation on total length of hospital stay, IgG anti-SARS-CoV-2 seroconversion, viral clearance from plasma and respiratory tract samples, and variations in Sequential Organ Failure Assessment score. The trial was analysed according to the intention-to-treat principle. RESULTS: 180 patients (133/180 [73.9%] males, mean age 66.6 years [IQR 57-73]) were enrolled a median of 8 days from onset of symptoms. At enrollment, 88.9% of patients showed moderate/severe respiratory failure. 30-days mortality was 20% in Control arm, 23% in Convalescent (risk ratio [RR] 1.13; 95% confidence interval [CI], 0.61-2.13, P = 0.694) and 25% in Standard plasma (RR 1.23; 95%CI, 0.63-2.37, P = 0.544). Time to viral clearance from respiratory tract was 21 days for Convalescent, 28 for Standard plasma and 23 in Control arm but differences were not statistically significant. No differences for other secondary endpoints were seen in the three arms. Serious adverse events were reported in 1.7%, 3.3% and 5% of patients in Control, Standard and Convalescent plasma arms respectively. CONCLUSIONS: Neither high-titer Convalescent nor Standard plasma improve outcomes of COVID-19 patients with acute respiratory failure. Trial Registration Clinicaltrials.gov Identifier: NCT04428021. First posted: 11/06/2020.

Usefulness of thromboelastometry in predicting the risk of bleeding in cirrhotics who undergo invasive procedures.

OBJECTIVES: The management of patients with liver cirrhosis undergoing invasive procedures is controversial and haemostasis assessment using routine laboratory is inappropriate. We evaluated the following: (a) the ability of thromboelastometry to predict the risk of bleeding in cirrhotic patients undergoing invasive procedures and enable a decision on the prophylactic transfusional strategy; (b) the contribution of platelet adhesion and aggregation tests in the assessment of haemostasis. PATIENTS AND METHODS: Seventeen cirrhotic patients undergoing invasive procedures were analyzed retrospectively (training set). To obtain preliminary data, an observational study was carried out in 58 patients (test set). All 75 patients were evaluated by thromboelastometry. Platelet adhesion and aggregation were evaluated in 16 patients using Multiplate, PFA-100 and Light Transmission Aggregometry. Factor VIII was dosed in all patients of the test set. RESULTS: In the training set, thromboelastometry confirmed the haemostatic assessment shown by the conventional test only in 6/17 (35%) patients. In the test set, thromboelastometry identified all patients who had a bleeding event. In patients with a high risk of bleeding, the use of thromboelastometry was cost-effective, reducing the platelet infusions by 64%. Platelet adhesion/aggregation abnormalities were observed in 15/16 (94%) patients, but bleeding events occurred only in 2/15 (13%) patients. CONCLUSION: Thromboelastometry appears to be useful to screen cirrhotic patients undergoing invasive procedures to identify the risk of bleeding and to optimize the transfusional strategy. Adhesion/aggregation tests are not useful in identifying patients at risk of bleeding and their application is not cost-effective.

Bridging therapy in antiphospholipid syndrome and antiphospholipid antibodies carriers: case series and review of the literature.

Peri-operative management of patients on warfarin involves assessing and balancing individual risks for thromboembolism and bleeding. The timing of warfarin withdrawal and a tailored pre/postoperative management (including the substitution of heparin in place of warfarin, the so-called bridging therapy) is critical in patients with prothrombotic conditions. The antiphospholipid syndrome (APS) is the most common cause of acquired thrombophilia. In this particular subset of patients, as the risk of thrombosis is higher than in general population, bridging therapy can represent a real challenge for treating physicians. Only few studies have been designed to address this topic. We aim to report our experience and to review the available literature in the peri-procedural management of APS and antiphospholipid antibody-positive patients, reporting adverse events and attempting to identify potential risk factor associated with thrombosis or bleeding complications.