Guidelines for the diagnosis and treatment of circulatory diseases in the context of the COVID-19 pandemic

The purpose of the study was to evaluate safety, effects on platelet aggregation and pharmacokinetics of F(ab')(2) fragments of anti-glycoprotein (GP) IIb-IIIa murine monoclonal antibody FRaMon (F(ab')(2) FRaMon) upon its intravenous administration in patients undergoing high-risk coronary angioplasty. Patients were treated before angioplasty with F(ab')(2) FRaMon at 0.2 mg/kg (n = 17) and 0.25 mg/kg (n = 12) bolus or with abciximab at 0.25 mg/kg bolus + 12 h infusion at 0.125 microg/kg per min (n = 29). F(ab')(2) FRaMon at both doses decreased platelet aggregation induced by 20 microM ADP to <10, <20, <40 and <70% of the predrug level at 1, 12, 24 and 72 h after injection, respectively. No significant differences were observed between F(ab')(2) FRaMon and abciximab antiaggregatory effects. In none of the patients did F(ab')(2) FRaMon cause allergic reactions, major bleedings or deep thrombocytopenia. Antibodies against F(ab')(2) FRaMon were detected in one patient. Free F(ab')(2) FRaMon was cleared from plasma within 12 h, while platelet-bound preparation occupied >95, 70-80 and 40-50% of GP IIb-IIIa at 1 and 12-24 h and 3 days after injection, respectively. Thrombotic complications within the first month after angioplasty in groups treated with F(ab')(2) FRaMon and abciximab were observed in one and two patients, respectively. The data obtained have shown that F(ab')(2) FRaMon at bolus administration to patients undergoing coronary angioplasty caused no serious side effects and at comparative dosage inhibited platelet aggregation with the same efficacy as abciximab at bolus + infusion administration.

Endorsed by: Research and Practical Council of the Ministry of Health of the Russian Federation.

Purpose. This multicenter, prospective registry evaluated the comparative safety and efficacy of left atrial appendage occlusion (LAAO) using the Watchman device (WD) and the Amplatzer Cardiac Plug (ACP) in patients with nonvalvular atrial fibrillation (NVAF) in real-world clinical practice in Russia. Methods. The study included data from 200 consecutive NVAF patients ( 66.8 ± 7.8 years, 44.5% female, median CHA2DS2VASc 4, median HAS-BLED 3) who had undergone LAAO implantation using WD ( n = 108 ) or ACP ( n = 92 ) from September 2015 to December 2017 in 5 medical centers in Russia. The primary safety endpoint was the procedure-related major adverse events, and the primary efficacy endpoint was the composite of thromboembolic events, device thrombosis, hemorrhagic events, and unexplained death during the 12-month follow-up. Results. Successful LAAO was performed in all 92 (100%) patients with ACP and 105 (97.2%) with WD ( p = 0.053 ). At 12 months, primary safety endpoint occurred in 6.5% of patients in the ACP group with no events in the WD group (6.5% vs. 0%, p = 0.008 ). During the 12-month follow-up, the primary efficacy endpoint has occurred in 8.3% of patients in the WD group ( n = 9 ) and 1.1% of patients in the ACP group ( n = 1 ) ( p = 0.016 ). Conclusions. In this multicenter prospective registry, LAA closure with the WD was associated with significantly higher thromboembolic events rate in NVAF patients. Patients, receiving the ACP, had more procedure-related major adverse events. However, further multicenter studies are necessary to evaluate these findings.

Activated platelets are involved in blood coagulation by exposing phosphatidylserine (PS), which serves as a substrate for assembling coagulation complexes. Platelets accelerate fibrin formation and thrombin generation, two final reactions of the coagulation cascade. We investigated the effects of antiplatelet drugs on platelet impact in these reactions and platelet ability to expose PS. Washed human platelets were incubated with acetylsalicylic acid (ASA), ticagrelor, ASA in combination with ticagrelor, ruciromab (glycoprotein IIb-IIIa antagonist), or prostaglandin E1 (PGE1). Platelets were not activated or activated by collagen and sedimented in multiwell plates, and plasma was added after supernatant removal. Fibrin formation (clotting) was monitored in a recalcification assay by light absorbance and thrombin generation in a fluorogenic test. PS exposure was assessed by annexin V staining using flow cytometry. Ticagrelor (alone and in combination with ASA), ruciromab, and PGE1, but not ASA, prolonged the lag phase and decreased the maximum rate of plasma clotting and decreased the peak and maximum rate of thrombin generation. Inhibition was observed when platelets were not treated with exogenous agonists (activation by endogenous thrombin) and pretreated with collagen. Ticagrelor (alone and in combination with ASA), ruciromab, and PGE1, but not ASA, decreased PS exposure on washed platelets activated by thrombin and by thrombin + collagen. PS exposure on activated platelets in whole blood was lower in patients with acute coronary syndrome receiving ticagrelor + ASA in comparison with donors free of medications. These results indicate that antiplatelet drugs are able to suppress platelet coagulation activity not only in vitro but also after administration to patients.