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Background: Some COVID-19 vaccinated individuals develop anti-platelet factor 4 (PF4) antibodies that cause thrombocytopenia and thrombosis;a rare syndrome referred to as vaccine-induced immune thrombotic thrombocytopenia (VITT). Currently, information on the characteristics and persistence of anti-PF4 antibodies that cause VITT after Ad26.COV2.S vaccination is limited, and available PF4-polyanion enzyme-linked immunosorbent assays (ELISAs) and functional diagnostic assays fail to differentiate Ad26.COV2.S and ChAdOx1 nCoV-19-associated VITT from similar clinical disorders, namely heparin-induced thrombocytopenia (HIT) and spontaneous HIT. Aim(s): Evaluate the persistence of anti-PF4 antibodies in Ad26. COV2.S-associated VITT and correlate findings with clinical and laboratory variables such as thrombosis and platelet counts. Develop/ investigate laboratory tools that differentiate VITT antibodies from HIT and spontaneous HIT. Method(s): Blood samples from VITT and HIT patient cohorts were tested in antigen-based and functional assays and correlated with clinical and laboratory features. Result(s): While Ad26.COV2.S-associated VITT patients were strongly positive in PF4-polyanion ELISAs;they were frequently negative in the serotonin release assay (4 of 8 tested patients were negative). In contrast, the PF4-dependent p-selectin expression assay (PEA) that uses PF4-treated platelets consistently diagnosed Ad26.COV2.S-associated VITT. Most Ad26.COV2.S-associated VITT antibodies persisted for >5 months in PF4-polyanion ELISAs, while the PEA became negative earlier. Two patients had otherwise unexplained mild persistent thrombocytopenia (140-150,000/ mul) six months after acute presentation. No recurrence of thrombosis was noted. Additionally, a novel un-complexed PF4 ELISA specifically differentiated VITT secondary to Ad26.COV2.S and ChAdOx1 nCoV-19 vaccination, from spontaneous HIT and HIT (Fig 1A-PF4/ polyanion ELISA;Fig 1B-Un-complexed PF4 ELISA;closed black circles-Ad26. COV2.S-associated VITT;closed red circle-ChAdOx1 nCoV-19-associated VITT;***p < 0.001;****p < 0.0001). Its specificity was further confirmed by testing commonly-encountered HIT-suspected patient samples that are PF4/polyanion ELISA-positive but negative in functional assays (1A-1B). Conclusion(s): Ad26.COV2.S-associated VITT antibodies are persistent, and the un-complexed PF4 ELISA appears to be both sensitive and specific for VITT diagnosis.
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The extracorporeal membrane oxygenation (ECMO) device was initially developed with the goal of providing extended support in patients experiencing cardiac failure. However, ECMO technology has evolved, and now provides a means to successfully manage patients experiencing cardiac and/or pulmonary failure until such time as the patient's body is able to either heal, or undergo transplantation. In addition, it has been used in the management of multisystem organ dysfunction. The life-saving utility of this therapy for critically ill patients has prompted world-wide implementation particularly in resource-rich settings. Innovations in instrumentation, broad clinical implementation, extensive utilization of blood and blood components, and the catastrophic nature of potential complications, have collectively prompted the evolution of a tremendous body of research. In this comprehensive review we briefly describe the early development of the ECMO device and technology, in addition to outlining the function of the device as it now commonly utilized including veno-arterial (VA) vs. veno-venous (VV) and rapid deployment ECMO. This review will also delineate the rationale for ECMO use, common clinical indications, and specialized techniques, in addition to the approaches necessary for their successful implementation. As systemic anticoagulation is frequently utilized to support patients on ECMO, the review also contains an extensive review of anticoagulation management, blood component utilization, and potential hematologic complications of ECMO. The review includes a discussion of more recent trends including the use of ECMO in COVID-19 patients, and the performance of tandem plasma exchange. Finally, areas of current controversy and needed research will be highlighted. © 2022 The authors.
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BACKGROUND: Convalescent plasma therapy for COVID-19 relies on transfer of anti-viral antibody from donors to recipients via plasma transfusion. The relationship between clinical characteristics and antibody response to COVID-19 is not well defined. We investigated predictors of convalescent antibody production and quantified recipient antibody response in a convalescent plasma therapy clinical trial. METHODS: Multivariable analysis of clinical and serological parameters in 103 confirmed COVID-19 convalescent plasma donors 28 days or more following symptom resolution was performed. Mixed-effects regression models with piecewise linear trends were used to characterize serial antibody responses in 10 convalescent plasma recipients with severe COVID-19. RESULTS: Donor antibody titres ranged from 0 to 1 : 3892 (anti-receptor binding domain (RBD)) and 0 to 1 : 3289 (anti-spike). Higher anti-RBD and anti-spike titres were associated with increased age, hospitalization for COVID-19, fever and absence of myalgia (all P < 0.05). Fatigue was significantly associated with anti-RBD (P = 0.03). In pairwise comparison amongst ABO blood types, AB donors had higher anti-RBD and anti-spike than O donors (P < 0.05). No toxicity was associated with plasma transfusion. Non-ECMO recipient anti-RBD antibody titre increased on average 31% per day during the first three days post-transfusion (P = 0.01) and anti-spike antibody titre by 40.3% (P = 0.02). CONCLUSION: Advanced age, fever, absence of myalgia, fatigue, blood type and hospitalization were associated with higher convalescent antibody titre to COVID-19. Despite variability in donor titre, 80% of convalescent plasma recipients showed significant increase in antibody levels post-transfusion. A more complete understanding of the dose-response effect of plasma transfusion amongst COVID-19-infected patients is needed.