RESUMEN
The role of veno-venous extracorporeal membrane oxygenation therapy (V-V ECMO) in severe COVID-19 acute respiratory distress syndrome (ARDS) is still under debate and conclusive data from large cohorts are scarce. Furthermore, criteria for the selection of patients that benefit most from this highly invasive and resource-demanding therapy are yet to be defined. In this study, we assess survival in an international multicenter cohort of COVID-19 patients treated with V-V ECMO and evaluate the performance of several clinical scores to predict 30-day survival. METHODS: This is an investigator-initiated retrospective non-interventional international multicenter registry study (NCT04405973, first registered 28 May 2020). In 127 patients treated with V-V ECMO at 15 centers in Germany, Switzerland, Italy, Belgium, and the United States, we calculated the Sequential Organ Failure Assessment (SOFA) Score, Simplified Acute Physiology Score II (SAPS II), Acute Physiology And Chronic Health Evaluation II (APACHE II) Score, Respiratory Extracorporeal Membrane Oxygenation Survival Prediction (RESP) Score, Predicting Death for Severe ARDS on VV ECMO (PRESERVE) Score, and 30-day survival. RESULTS: In our study cohort which enrolled 127 patients, overall 30-day survival was 54%. Median SOFA, SAPS II, APACHE II, RESP, and PRESERVE were 9, 36, 17, 1, and 4, respectively. The prognostic accuracy for all these scores (area under the receiver operating characteristic-AUROC) ranged between 0.548 and 0.605. CONCLUSIONS: The use of scores for the prediction of mortality cannot be recommended for treatment decisions in severe COVID-19 ARDS undergoing V-V ECMO; nevertheless, scoring results below or above a specific cut-off value may be considered as an additional tool in the evaluation of prognosis. Survival rates in this cohort of COVID-19 patients treated with VV ECMO were slightly lower than those reported in non-COVID-19 ARDS patients treated with V-V ECMO.
RESUMEN
The platelet receptor glycoprotein (GP) IIb/IIIa, formed by integrins αIIb and ß3, plays an important role in platelet adhesion and aggregation. Its major binding site is the arginine-glycine-aspartic acid (RGD) sequence present in several adhesive proteins. Upon platelet activation, inside-out signaling activates the complex permitting binding to RGD motif containing proteins, such as von Willebrand factor (VWF). VWF is a large multidomain plasma GP essential to primary hemostasis, which can directly interact with platelets because it exhibits binding sites for GPIbα and GPIIb/IIIa in its A1 and C4 domain, respectively. A vast variety of VWF variants have been identified in which domain-specific mutations affect distinct functions of VWF but reduced GPIIb/IIIa binding has barely been studied so far. Here, we strived to investigate the influence of C domain mutations, which have been identified in patients diagnosed with von Willebrand disease (VWD), on VWF-GPIIb/IIIa interaction. To determine binding to membrane-incorporated GPIIb/IIIa in the absence of GPIbα, we developed and validated a cell-based binding assay which uses HEK293 cells stably expressing a constitutively active form of the GPIIb/IIIa receptor complex on their plasma membrane. By employing this assay, we measured GPIIb/IIIa binding of 14 VWF C domain mutants identified in VWD patients. Mutants p.Cys2257Arg, p.Gly2441Cys, p.Cys2477Tyr, and p.Pro2722Ala exhibited significantly reduced binding. Summarizing, we have developed a useful research tool to specifically investigate GPIIb/IIIa interaction with its protein binding partners and identified four VWF variants that exhibit impaired GPIIb/IIIa binding. At least in the homozygous state, this defect could contribute to the VWD phenotype.
Asunto(s)
Plaquetas/fisiología , Mutación Missense/genética , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria/metabolismo , Dominios Proteicos/genética , Enfermedades de von Willebrand/genética , Factor de von Willebrand/genética , Anticuerpos Monoclonales/metabolismo , Fibrinógeno/metabolismo , Variación Genética , Células HEK293 , Humanos , Activación Plaquetaria , Unión Proteica , Ingeniería de Proteínas , Transducción de Señal , Enfermedades de von Willebrand/metabolismoRESUMEN
AIMS: Acquired von Willebrand syndrome (aVWS) is a common complication of severe aortic valve stenosis and can be corrected by surgical valve replacement. Transcatheter aortic valve implantation (TAVI) is gaining importance, but the influence of this new technique on aVWS has never been examined. The objective of this study was to assess the impact of TAVI on aVWS. METHODS: We enrolled 15 patients with severe aortic stenosis and high surgical risk admitted for elective TAVI. All patients were successfully treated by TAVI, using either the transfemoral (n = 6) or transapical approach (n = 9). Patients were screened for aVWS by measuring PFA-100 in vitro closure time, von Willebrand factor (VWF) antigen, VWF function, and VWF multimer analysis. Analyses were then repeated 30 minutes, 24 hours, and 7 days after valve replacement. RESULTS: Fourteen of 15 patients showed pathologic alterations of VWF. An inverse correlation was observed between the transvalvular pressure gradient and VWF high-molecular-weight multimers (VWF:HMWM) (r = -0.621; P=.01), which are essential for the platelet dependent hemostatic function of VWF. Transaortic gradient was significantly reduced in all patients following TAVI. Hemostaseologic findings improved in all patients following TAVI, the percentage of VWF:HMWM increased (19.05 ± 5.19% before TAVI to 24.08 ± 4.75% (P=.04) on day 7 post TAVI), and the multimer pattern normalized. CONCLUSIONS: Acquired von Willebrand syndrome due to aortic valve stenosis can successfully be corrected by TAVI.