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2. Thrombotic and bleeding complications in patients with chronic lymphocytic leukemia and severe COVID-19: a study of ERIC, the European Research Initiative on CLL

Author

Antic, D. Milic, N. Chatzikonstantinou, T. Scarfò, L. Otasevic, V. Rajovic, N. Allsup, D. Alonso Cabrero, A. Andres, M. Baile Gonzales, M. Capasso, A. Collado, R. Cordoba, R. Cuéllar-García, C. Correa, J.G. De Paoli, L. De Paolis, M.R. Del Poeta, G. Dimou, M. Doubek, M. Efstathopoulou, M. El-Ashwah, S. Enrico, A. Espinet, B. Farina, L. Ferrari, A. Foglietta, M. Lopez-Garcia, A. García-Marco, J.A. García-Serra, R. Gentile, M. Gimeno, E. da Silva, M.G. Gutwein, O. Hakobyan, Y.K. Herishanu, Y. Hernández-Rivas, J.Á. Herold, T. Itchaki, G. Jaksic, O. Janssens, A. Kalashnikova, O.B. Kalicińska, E. Kater, A.P. Kersting, S. Koren-Michowitz, M. Labrador, J. Lad, D. Laurenti, L. Fresa, A. Levin, M.-D. Mayor Bastida, C. Malerba, L. Marasca, R. Marchetti, M. Marquet, J. Mihaljevic, B. Milosevic, I. Mirás, F. Morawska, M. Motta, M. Munir, T. Murru, R. Nunes, R. Olivieri, J. Pavlovsky, M.A. Piskunova, I. Popov, V.M. Quaglia, F.M. Quaresmini, G. Reda, G. Rigolin, G.M. Shrestha, A. Šimkovič, M. Smirnova, S. Špaček, M. Sportoletti, P. Stanca, O. Stavroyianni, N. Te Raa, D. Tomic, K. Tonino, S. Trentin, L. Van Der Spek, E. van Gelder, M. Varettoni, M. Visentin, A. Vitale, C. Vukovic, V. Wasik-Szczepanek, E. Wróbel, T. Segundo, L.Y.S. Yassin, M. Coscia, M. Rambaldi, A. Montserrat, E. Foà, R. Cuneo, A. Carrier, M. Ghia, P. Stamatopoulos, K. and Antic, D. Milic, N. Chatzikonstantinou, T. Scarfò, L. Otasevic, V. Rajovic, N. Allsup, D. Alonso Cabrero, A. Andres, M. Baile Gonzales, M. Capasso, A. Collado, R. Cordoba, R. Cuéllar-García, C. Correa, J.G. De Paoli, L. De Paolis, M.R. Del Poeta, G. Dimou, M. Doubek, M. Efstathopoulou, M. El-Ashwah, S. Enrico, A. Espinet, B. Farina, L. Ferrari, A. Foglietta, M. Lopez-Garcia, A. García-Marco, J.A. García-Serra, R. Gentile, M. Gimeno, E. da Silva, M.G. Gutwein, O. Hakobyan, Y.K. Herishanu, Y. Hernández-Rivas, J.Á. Herold, T. Itchaki, G. Jaksic, O. Janssens, A. Kalashnikova, O.B. Kalicińska, E. Kater, A.P. Kersting, S. Koren-Michowitz, M. Labrador, J. Lad, D. Laurenti, L. Fresa, A. Levin, M.-D. Mayor Bastida, C. Malerba, L. Marasca, R. Marchetti, M. Marquet, J. Mihaljevic, B. Milosevic, I. Mirás, F. Morawska, M. Motta, M. Munir, T. Murru, R. Nunes, R. Olivieri, J. Pavlovsky, M.A. Piskunova, I. Popov, V.M. Quaglia, F.M. Quaresmini, G. Reda, G. Rigolin, G.M. Shrestha, A. Šimkovič, M. Smirnova, S. Špaček, M. Sportoletti, P. Stanca, O. Stavroyianni, N. Te Raa, D. Tomic, K. Tonino, S. Trentin, L. Van Der Spek, E. van Gelder, M. Varettoni, M. Visentin, A. Vitale, C. Vukovic, V. Wasik-Szczepanek, E. Wróbel, T. Segundo, L.Y.S. Yassin, M. Coscia, M. Rambaldi, A. Montserrat, E. Foà, R. Cuneo, A. Carrier, M. Ghia, P. Stamatopoulos, K.

Abstract

Background: Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to COVID-19 related poor outcomes, including thrombosis and death, due to the advanced age, the presence of comorbidities, and the disease and treatment-related immune deficiency. The aim of this study was to assess the risk of thrombosis and bleeding in patients with CLL affected by severe COVID-19. Methods: This is a retrospective multicenter study conducted by ERIC, the European Research Initiative on CLL, including patients from 79 centers across 22 countries. Data collection was conducted between April and May 2021. The COVID-19 diagnosis was confirmed by the real-time polymerase chain reaction (RT-PCR) assay for SARS-CoV-2 on nasal or pharyngeal swabs. Severe cases of COVID-19 were defined by hospitalization and the need of oxygen or admission into ICU. Development and type of thrombotic events, presence and severity of bleeding complications were reported during treatment for COVID-19. Bleeding events were classified using ISTH definition. STROBE recommendations were used in order to enhance reporting. Results: A total of 793 patients from 79 centers were included in the study with 593 being hospitalized (74.8%). Among these, 511 were defined as having severe COVID: 162 were admitted to the ICU while 349 received oxygen supplementation outside the ICU. Most patients (90.5%) were receiving thromboprophylaxis. During COVID-19 treatment, 11.1% developed a thromboembolic event, while 5.0% experienced bleeding. Thrombosis developed in 21.6% of patients who were not receiving thromboprophylaxis, in contrast to 10.6% of patients who were on thromboprophylaxis. Bleeding episodes were more frequent in patients receiving intermediate/therapeutic versus prophylactic doses of low-molecular-weight heparin (LWMH) (8.1% vs. 3.8%, respectively) and in elderly. In multivariate analysis, peak D-dimer level and C-reactive protein to albumin ratio were poor prognostic factors for thrombosis occu

Published
2022

3. Thrombotic and bleeding complications in patients with chronic lymphocytic leukemia and severe COVID-19: a study of ERIC, the European Research Initiative on CLL

Author

Antic, D., Milic, N., Chatzikonstantinou, T., Scarfo, L., Otasevic, V., Rajovic, N., Allsup, D., Alonso Cabrero, A., Andres, M., Baile Gonzales, M., Capasso, A., Collado, R., Cordoba, R., Cuellar-Garcia, C., Correa, J. G., De Paoli, L., De Paolis, M. R., Del Poeta, G., Dimou, M., Doubek, M., Efstathopoulou, M., El-Ashwah, S., Enrico, A., Espinet, B., Farina, L., Ferrari, A., Foglietta, M., Lopez-Garcia, A., Garcia-Marco, J. A., Garcia-Serra, R., Gentile, Marino, Gimeno, E., da Silva, M. G., Gutwein, O., Hakobyan, Y. K., Herishanu, Y., Hernandez-Rivas, J. A., Herold, T., Itchaki, G., Jaksic, O., Janssens, A., Kalashnikova, O. B., Kalicinska, E., Kater, A. P., Kersting, S., Koren-Michowitz, M., Labrador, J., Lad, D., Laurenti, Luca, Fresa, Alberto, Levin, M. -D., Mayor Bastida, C., Malerba, L., Marasca, R., Marchetti, M., Marquet, J., Mihaljevic, B., Milosevic, I., Miras, F., Morawska, M., Motta, M., Munir, T., Murru, R., Nunes, R., Olivieri, J., Pavlovsky, M. A., Piskunova, I., Popov, V. M., Quaglia, F. M., Quaresmini, G., Reda, G., Rigolin, G. M., Shrestha, A., Simkovic, M., Smirnova, S., Spacek, M., Sportoletti, P., Stanca, O., Stavroyianni, N., Te Raa, D., Tomic, K., Tonino, S., Trentin, L., Van Der Spek, E., van Gelder, M., Varettoni, M., Visentin, A., Vitale, C., Vukovic, Vladimir, Wasik-Szczepanek, E., Wrobel, T., Segundo, L. Y. S., Yassin, M., Coscia, M., Rambaldi, A., Montserrat, E., Foa, Robin, Cuneo, A., Carrier, M., Ghia, P., Stamatopoulos, K., Gentile M., Laurenti L. (ORCID:0000-0002-8327-1396), Fresa A., Vukovic V. (ORCID:0000-0002-9561-7825), Foa R., Antic, D., Milic, N., Chatzikonstantinou, T., Scarfo, L., Otasevic, V., Rajovic, N., Allsup, D., Alonso Cabrero, A., Andres, M., Baile Gonzales, M., Capasso, A., Collado, R., Cordoba, R., Cuellar-Garcia, C., Correa, J. G., De Paoli, L., De Paolis, M. R., Del Poeta, G., Dimou, M., Doubek, M., Efstathopoulou, M., El-Ashwah, S., Enrico, A., Espinet, B., Farina, L., Ferrari, A., Foglietta, M., Lopez-Garcia, A., Garcia-Marco, J. A., Garcia-Serra, R., Gentile, Marino, Gimeno, E., da Silva, M. G., Gutwein, O., Hakobyan, Y. K., Herishanu, Y., Hernandez-Rivas, J. A., Herold, T., Itchaki, G., Jaksic, O., Janssens, A., Kalashnikova, O. B., Kalicinska, E., Kater, A. P., Kersting, S., Koren-Michowitz, M., Labrador, J., Lad, D., Laurenti, Luca, Fresa, Alberto, Levin, M. -D., Mayor Bastida, C., Malerba, L., Marasca, R., Marchetti, M., Marquet, J., Mihaljevic, B., Milosevic, I., Miras, F., Morawska, M., Motta, M., Munir, T., Murru, R., Nunes, R., Olivieri, J., Pavlovsky, M. A., Piskunova, I., Popov, V. M., Quaglia, F. M., Quaresmini, G., Reda, G., Rigolin, G. M., Shrestha, A., Simkovic, M., Smirnova, S., Spacek, M., Sportoletti, P., Stanca, O., Stavroyianni, N., Te Raa, D., Tomic, K., Tonino, S., Trentin, L., Van Der Spek, E., van Gelder, M., Varettoni, M., Visentin, A., Vitale, C., Vukovic, Vladimir, Wasik-Szczepanek, E., Wrobel, T., Segundo, L. Y. S., Yassin, M., Coscia, M., Rambaldi, A., Montserrat, E., Foa, Robin, Cuneo, A., Carrier, M., Ghia, P., Stamatopoulos, K., Gentile M., Laurenti L. (ORCID:0000-0002-8327-1396), Fresa A., Vukovic V. (ORCID:0000-0002-9561-7825), and Foa R.

Abstract

Background: Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to COVID-19 related poor outcomes, including thrombosis and death, due to the advanced age, the presence of comorbidities, and the disease and treatment-related immune deficiency. The aim of this study was to assess the risk of thrombosis and bleeding in patients with CLL affected by severe COVID-19. Methods: This is a retrospective multicenter study conducted by ERIC, the European Research Initiative on CLL, including patients from 79 centers across 22 countries. Data collection was conducted between April and May 2021. The COVID-19 diagnosis was confirmed by the real-time polymerase chain reaction (RT-PCR) assay for SARS-CoV-2 on nasal or pharyngeal swabs. Severe cases of COVID-19 were defined by hospitalization and the need of oxygen or admission into ICU. Development and type of thrombotic events, presence and severity of bleeding complications were reported during treatment for COVID-19. Bleeding events were classified using ISTH definition. STROBE recommendations were used in order to enhance reporting. Results: A total of 793 patients from 79 centers were included in the study with 593 being hospitalized (74.8%). Among these, 511 were defined as having severe COVID: 162 were admitted to the ICU while 349 received oxygen supplementation outside the ICU. Most patients (90.5%) were receiving thromboprophylaxis. During COVID-19 treatment, 11.1% developed a thromboembolic event, while 5.0% experienced bleeding. Thrombosis developed in 21.6% of patients who were not receiving thromboprophylaxis, in contrast to 10.6% of patients who were on thromboprophylaxis. Bleeding episodes were more frequent in patients receiving intermediate/therapeutic versus prophylactic doses of low-molecular-weight heparin (LWMH) (8.1% vs. 3.8%, respectively) and in elderly. In multivariate analysis, peak D-dimer level and C-reactive protein to albumin ratio were poor prognostic factors for thrombosis occu

Published
2022

4. Thrombotic and bleeding complications in patients with chronic lymphocytic leukemia and severe COVID-19: a study of ERIC, the European Research Initiative on CLL

Author

Antic D, Milic N, Chatzikonstantinou T, Scarfò L, Otasevic V, Rajovic N, Allsup D, Alonso Cabrero A, Andres M, Baile Gonzales M, Capasso A, Collado R, Cordoba R, Cuéllar-García C, Correa JG, De Paoli L, De Paolis MR, Del Poeta G, Dimou M, Doubek M, Efstathopoulou M, El-Ashwah S, Enrico A, Espinet B, Farina L, Ferrari A, Foglietta M, Lopez-Garcia A, García-Marco JA, García-Serra R, Gentile M, Gimeno E, da Silva MG, Gutwein O, Hakobyan YK, Herishanu Y, Hernández-Rivas JÁ, Herold T, Itchaki G, Jaksic O, Janssens A, Kalashnikova OB, Kalicińska E, Kater AP, Kersting S, Koren- Michowitz M, Labrador J, Lad D, Laurenti L, Fresa A, Levin MD, Mayor Bastida C, Malerba L, Marasca R, Marchetti M, Marquet J, Mihaljevic B, Milosevic I, Mirás F, Morawska M, Motta M, Munir T, Murru R, Nunes R, Olivieri J, Pavlovsky MA, Piskunova I, Popov VM, Quaglia FM, Quaresmini G, Reda G, Rigolin GM, Shrestha A, Šimkovič M, Smirnova S, Špaček M, Sportoletti P, Stanca O, Stavroyianni N, Te Raa D, Tomic K, Tonino S, Trentin L, Van Der Spek E, van Gelder M, Varettoni M, Visentin A, Vitale C, Vukovic V, Wasik-Szczepanek E, Wróbel T, Segundo LYS, Yassin M, Coscia M, Rambaldi A, Montserrat E, Foà R, Cuneo A, Carrier M, Ghia P, Stamatopoulos K.

Subjects
Age, Anticoagulation therapy, Bleeding, CLL, COVID-19, D-dimer, LMWH, Thromboprophylaxis, Thrombosis
Abstract

Background: Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to COVID-19 related poor outcomes, including thrombosis and death, due to the advanced age, the presence of comorbidities, and the disease and treatment- related immune deficiency. The aim of this study was to assess the risk of thrombosis and bleeding in patients with CLL affected by severe COVID-19. Methods: This is a retrospective multicenter study conducted by ERIC, the European Research Initiative on CLL, including patients from 79 centers across 22 countries. Data collection was conducted between April and May 2021. The COVID-19 diagnosis was confirmed by the real-time polymerase chain reaction (RT-PCR) assay for SARS- CoV-2 on nasal or pharyngeal swabs. Severe cases of COVID-19 were defined by hospitalization and the need of oxygen or admission into ICU. Development and type of thrombotic events, presence and severity of bleeding complications were reported during treatment for COVID-19. Bleeding events were classified using ISTH definition. STROBE recommendations were used in order to enhance reporting. Results: A total of 793 patients from 79 centers were included in the study with 593 being hospitalized (74.8%). Among these, 511 were defined as having severe COVID: 162 were admitted to the ICU while 349 received oxygen supplementation outside the ICU. Most patients (90.5%) were receiving thromboprophylaxis. During COVID-19 treatment, 11.1% developed a thromboembolic event, while 5.0% experienced bleeding. Thrombosis developed in 21.6% of patients who were not receiving thromboprophylaxis, in contrast to 10.6% of patients who were on thromboprophylaxis. Bleeding episodes were more frequent in patients receiving intermediate/therapeutic versus prophylactic doses of low-molecular-weight heparin (LWMH) (8.1% vs. 3.8%, respectively) and in elderly. In multivariate analysis, peak D-dimer level and C- reactive protein to albumin ratio were poor prognostic factors for thrombosis occurrence (OR = 1.022, 95%CI 1.007‒1.038 and OR = 1.025, 95%CI 1.001‒1.051, respectively), while thromboprophylaxis use was protective (OR = 0.199, 95%CI 0.061‒0.645). Age and LMWH intermediate/therapeutic dose administration were prognostic factors in multivariate model for bleeding (OR = 1.062, 95%CI 1.017-1.109 and OR = 2.438, 95%CI 1.023-5.813, respectively). Conclusions: Patients with CLL affected by severe COVID-19 are at a high risk of thrombosis if thromboprophylaxis is not used, but also at increased risk of bleeding under the LMWH intermediate/therapeutic dose administration.

Published
2022

14. Adult B-cell acute lymphoblastic leukemias: Conclusions of the Russian prospective multicenter study ALL-2009

Author

Parovichnikova, E N, primary, Troitskaya, V V, additional, Sokolov, A N, additional, Bondarenko, S N, additional, Gavrilina, O A, additional, Baskhaeva, G A, additional, Biderman, B V, additional, Lukyanova, I A, additional, Kuz'mina, L A, additional, Klyasova, G A, additional, Kravchenko, S K, additional, Gribanova, E O, additional, Zvonkov, E E, additional, Akhmerzaeva, Z Kh, additional, Baranova, O Yu, additional, Kaporskaya, T S, additional, Ryltsova, T V, additional, Zotina, E N, additional, Zinina, E E, additional, Samoilova, O S, additional, Kaplanov, K D, additional, Gavrilova, L V, additional, Konstantinova, T S, additional, Lapin, V A, additional, Pristupa, A S, additional, Eluferyeva, A S, additional, Obukhova, T N, additional, Piskunova, I S, additional, Gal'tseva, I V, additional, Dvirnyk, V N, additional, Rusinov, M A, additional, Kulikov, S M, additional, and Savchenko, V G, additional

Published
2017
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29. Cyclic hydrazides

Author

Rozhkov, E., primary, Piskunova, I., additional, Gol'd, M., additional, and Kalvin'sh, I., additional

Published
1998
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34. Synthesis and Quantitative Structure−Activity Relationship of Hydrazones of N-Amino-N‘-hydroxyguanidine as Electron Acceptors for Xanthine Oxidase

Author

Prusis, P., Dambrova, M., Andrianov, V., Rozhkov, E., Semenikhina, V., Piskunova, I., Ongwae, E., Lundstedt, T., Kalvinsh, I., and Wikberg, J. E. S.

Abstract

A series of new N-hydroxyguanidines were synthesized and tested for electron acceptor activity on bovine milk xanthine oxidase using xanthine as reducing substrate. Manual inspection of the structure−activity data revealed that molecules containing nitro groups (“set A”) show a different structure−activity relationship pattern compared to non-nitro compounds (“set B”). Accordingly separate QSAR models were built and validated for the two sets. Substantial differences were found in properties governing acceptor activity for the models, the only common property being sterical access to the imino nitrogen atom of the hydroxyguanidinimines. For set A molecules the presence of a nitro substituent at a certain distance range from the hydroxuguanidino group was most important. In addition, the presence of a nitro group in the ortho position interacting with NH2 of the hydroxyguanidino group, and the mutual geometry of the phenyl ring, hydroxyguanidine, and imine groups was important for this set. By contrast, for set B molecules the acceptor activity was most influenced by the geometry of methoxy groups and the size and geometry of meta and para substituents of the phenyl ring.

Published
2004

48. 13C and 15N NMR spectra of 2,3-substituted 2H-azirines

Author

Liepin'sh, é. é., él'kinson, R. S., Piskunova, I. P., and Eremeev, A. V.

Abstract

The 13C and 15N NMR spectra of a series of 2,3-substituted 2H-azirines have been studied. The 15N chemical shift for the nitrogen in the azirine ring is found at much higher field than in acyclic imines with a considerable electronic effect for the substituents on the double bond. Cooperative steric and electronic effects associated with substituents on the unsaturated carbon atom of the ring were found to influence the shielding of the 13C and 15N nuclei. Reaction constants have been calculated for 2-alkyl(aryl)-3-phenylazirines. It has been shown that the azirine ring has a powerful —I effect (when compared with the phenyl ring) that exceeds the analogous value for the cyano group.

Published
1986
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