ABSTRACT
Breakthrough hemolysis (BTH) is the return of hemolytic disease resulting in an overall increase in complement activation in a patient being treated for paroxysmal nocturnal hemoglobinuria (PNH) with complement inhibitors (CI). BTH after COVID-19 vaccination has only been reported in PNH patients treated with the traditional C5 CI eculizumab and ravulizumab. We report on a new association of BTH in a newly COVID-19 vaccinated, previously stable PNH patient treated with pegcetacoplan, a C3 CI. The patient is a 29-year-old female diagnosed with PNH in 2017 and was started on eculizumab but was switched to pegcetacoplan in 2021 after continuing to exhibit symptomatic hemolysis. Subsequently, the patient returned to PNH remission serologically and symptomatically until her first COVID-19 vaccination. Since then, her lactate dehydrogenase (LDH) and hemoglobin counts have not fully returned to previous baseline levels, with significant exacerbations after her second COVID-19 vaccine and de novo COVID-19 infection. As of May 2022, the patient requires packed red blood cell transfusions every two to three months and has undergone a bone marrow transplant evaluation. This case study suggests that the administration of the upstream C3 CI, pegcetacoplan, is associated with active extravascular hemolysis in the setting of COVID-19 vaccinations and active COVID-19 infection. The pathophysiology of this hemolysis is unclear as hemolysis could be related to the underlying complement factor deficiency or amplification of complement factors causing extravascular hemolysis. There are conflicting reports in the literature regarding the mechanism by which COVID-19 vaccination and infection cause BTH in PNH patients, regardless of the choice of CI treatment. Bringing awareness to this case of BTH secondary to COVID-19 in a PNH patient treated with pegcetacoplan can further warrant the investigation of the role of COVID-19 in complement disruption and its role in BTH.
ABSTRACT
The proceedings contain 46 papers. The topics discussed include: anemia assessment with benchmarking of red blood cell transfusion risk in cardiac surgery;clinical outcomes and therapeutic strategies for gastrointestinal bleeding in patients who decline transfusion;effect of patient blood management program on outcomes of the elderly with femur fracture who underwent orthopedic surgery;effect of ultrafiltration during cardiopulmonary bypass on viscoelastic profiles in cardiac surgery: retrospective analysis;hemoglobin based oxygen carrier treatment and clinical outcomes in severe anemia when blood is not an option;hemoglobin, lactate dehydrogenase, and FACIT-fatigue normalization in pegcetacoplan-treated patients with paroxysmal nocturnal hemoglobinuria;implementing three key blood management measures during COVID-19 related inventory shortages;and managing preoperative anemia using a novel algorithm to determine the preoperative target hemoglobin.
ABSTRACT
The proceedings contain 252 papers. The topics discussed include: immunogenicity of Covid-19 vaccination in patients with myelodysplastic syndromes;antibody responses to SARS-CoV-2 vaccination in patients with acute leukemia and high-risk MDS on active anti-cancer therapies;CD9 derepression drives cellular differentiation and restores immune recognition in pediatric acute myeloid leukemia;follow-up of patients with FLT3-mutated relapsed or refractory acute myeloid leukemia in the phase 3 ADMIRAL trial;efficacy and safety of Maribavir as a rescue treatment for investigator assigned therapy in transplant recipients with refractory or resistant cytomegalovirus infections in the SOLSTICE study: phase 3 trial results;long-term survival benefit of eculizumab treatment in patients with paroxysmal nocturnal hemoglobinuria: data from the international PNH registry;and analysis of anemia persistence and related adverse events in patients with paroxysmal nocturnal hemoglobinuria treated with pegcetacoplan.
ABSTRACT
From the medical, pharmaceutical, and social perspectives, 2021 has been a year dominated by the COVID-19 pandemic. However, despite this global health crisis, the pharmaceutical industry has continued its endeavors, and 2021 could be considered an excellent year in terms of the drugs accepted by the US Food and Drug Administration (FDA). Thus, during this year, the FDA has approved 50 novel drugs, of which 36 are new chemical entities and 14 biologics. It has also authorized 10 TIDES (8 peptides, 2 oligonucleotides), in addition to 2 antibody-drug conjugates (ADCs) whose structures contain peptides. Thus, TIDES have accounted for about 24% of the approvals in the various drug categories. Importantly, this percentage has surpassed the figure in 2020 (10%), thus reflecting the remarkable success of TIDES. In this review, the approved TIDE-based drugs are analyzed on the basis of their chemical structure, medical target, mode of action, administration route, and adverse effects.