Reversal of the anticoagulant and anti-hemostatic effect of low molecular weight heparin by direct prothrombin activation
Autor(a) principal: | |
---|---|
Data de Publicação: | 2012 |
Outros Autores: | , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1590/S0100-879X2012007500108 http://hdl.handle.net/11449/40593 |
Resumo: | Lopap, found in the bristles of Lonomia obliqua caterpillar, is the first exogenous prothrombin activator that shows serine protease-like activity, independent of prothrombinase components and unique lipocalin reported to interfere with hemostasis mechanisms. To assess the action of an exogenous prothrombin activator reversing the anticoagulant and antihemostatic effect induced by low molecular weight heparin (LMWH), male New Zealand rabbits (N = 20, weighing 3.8-4.0 kg) allocated to 4 groups were anticoagulated with 1800 IU/kg LMWH (iv) over 2 min, followed by iv administration of saline or recombinant Lopap (rLopap) at 1 mu g/kg (LG1) or 10 mu g/kg (LG10), 10 min after the injection of LMWH, in a blind manner. Control animals were treated only with saline. The action of rLopap was assessed in terms of activated partial thromboplastin time (aPTT), prothrombin fragment F1+2, fibrinogen, and ear puncture bleeding time (BT) at 5, 10, 15, 17, 20, 30, 40, 60, and 90 min after initiation of LMWH infusion. LG10 animals showed a decrease of aPTT in more than 50% and BT near to normal baseline. The level of prothrombin fragment F1+2 measured by ELISA had a 6-fold increase with rLopap treatment (10 mu g/kg) and was inversely proportional to BT in LMWH-treated animals. Thus, Lopap, obtained in recombinant form using E. coli expression system, was useful in antagonizing the effect of LMWH through direct prothrombin activation, which can be a possible strategy for the reversal of bleeding and anticoagulant events. |
id |
UNSP_9519c0a4bca23499d4fad6b0c26b702e |
---|---|
oai_identifier_str |
oai:repositorio.unesp.br:11449/40593 |
network_acronym_str |
UNSP |
network_name_str |
Repositório Institucional da UNESP |
repository_id_str |
2946 |
spelling |
Reversal of the anticoagulant and anti-hemostatic effect of low molecular weight heparin by direct prothrombin activationProthrombin activationProcoagulantExogenous hemostatic factorrLopapBleedingAnticoagulantLopap, found in the bristles of Lonomia obliqua caterpillar, is the first exogenous prothrombin activator that shows serine protease-like activity, independent of prothrombinase components and unique lipocalin reported to interfere with hemostasis mechanisms. To assess the action of an exogenous prothrombin activator reversing the anticoagulant and antihemostatic effect induced by low molecular weight heparin (LMWH), male New Zealand rabbits (N = 20, weighing 3.8-4.0 kg) allocated to 4 groups were anticoagulated with 1800 IU/kg LMWH (iv) over 2 min, followed by iv administration of saline or recombinant Lopap (rLopap) at 1 mu g/kg (LG1) or 10 mu g/kg (LG10), 10 min after the injection of LMWH, in a blind manner. Control animals were treated only with saline. The action of rLopap was assessed in terms of activated partial thromboplastin time (aPTT), prothrombin fragment F1+2, fibrinogen, and ear puncture bleeding time (BT) at 5, 10, 15, 17, 20, 30, 40, 60, and 90 min after initiation of LMWH infusion. LG10 animals showed a decrease of aPTT in more than 50% and BT near to normal baseline. The level of prothrombin fragment F1+2 measured by ELISA had a 6-fold increase with rLopap treatment (10 mu g/kg) and was inversely proportional to BT in LMWH-treated animals. Thus, Lopap, obtained in recombinant form using E. coli expression system, was useful in antagonizing the effect of LMWH through direct prothrombin activation, which can be a possible strategy for the reversal of bleeding and anticoagulant events.Instituto de Ensino e PesquisaHospital Sirio LibanesFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)CAT/CEPIDConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Inst Butantan, Lab Bioquim & Biofis, BR-05503900 São Paulo, BrazilCET Hosp Sirio Libanes, Serv Med Anestesia, São Paulo, BrazilUniv Estadual Paulista, Fac Med Botucatu, Botucatu, SP, BrazilHosp Santa Catarina, Ctr Estudos & Pesquisas, São Paulo, BrazilUniv Estadual Paulista, Fac Med Botucatu, Botucatu, SP, BrazilFAPESP: 10/00600-0Associação Brasileira de Divulgação Científica (ABRADIC)Instituto ButantanCET Hosp Sirio LibanesUniversidade Estadual Paulista (Unesp)Hosp Santa CatarinaAndrade, S. A.Carrijo-Carvalho, L. C.Peceguini, L. A. M.Wlian, L.Sato, A. C.Luchiari, C.Silva, E. D.Maffei, Francisco Humberto de Abreu [UNESP]Chudzinski-Tavassi, A. M.2014-05-20T15:31:28Z2014-05-20T15:31:28Z2012-10-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article929-934http://dx.doi.org/10.1590/S0100-879X2012007500108Brazilian Journal of Medical and Biological Research. São Paulo: Assoc Bras Divulg Cientifica, v. 45, n. 10, p. 929-934, 2012.0100-879Xhttp://hdl.handle.net/11449/4059310.1590/S0100-879X2012007500108S0100-879X2012007500108WOS:000308408600007Web of Sciencereponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengBrazilian Journal of Medical and Biological Research1.492info:eu-repo/semantics/openAccess2021-10-23T07:07:42Zoai:repositorio.unesp.br:11449/40593Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462021-10-23T07:07:42Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Reversal of the anticoagulant and anti-hemostatic effect of low molecular weight heparin by direct prothrombin activation |
title |
Reversal of the anticoagulant and anti-hemostatic effect of low molecular weight heparin by direct prothrombin activation |
spellingShingle |
Reversal of the anticoagulant and anti-hemostatic effect of low molecular weight heparin by direct prothrombin activation Andrade, S. A. Prothrombin activation Procoagulant Exogenous hemostatic factor rLopap Bleeding Anticoagulant |
title_short |
Reversal of the anticoagulant and anti-hemostatic effect of low molecular weight heparin by direct prothrombin activation |
title_full |
Reversal of the anticoagulant and anti-hemostatic effect of low molecular weight heparin by direct prothrombin activation |
title_fullStr |
Reversal of the anticoagulant and anti-hemostatic effect of low molecular weight heparin by direct prothrombin activation |
title_full_unstemmed |
Reversal of the anticoagulant and anti-hemostatic effect of low molecular weight heparin by direct prothrombin activation |
title_sort |
Reversal of the anticoagulant and anti-hemostatic effect of low molecular weight heparin by direct prothrombin activation |
author |
Andrade, S. A. |
author_facet |
Andrade, S. A. Carrijo-Carvalho, L. C. Peceguini, L. A. M. Wlian, L. Sato, A. C. Luchiari, C. Silva, E. D. Maffei, Francisco Humberto de Abreu [UNESP] Chudzinski-Tavassi, A. M. |
author_role |
author |
author2 |
Carrijo-Carvalho, L. C. Peceguini, L. A. M. Wlian, L. Sato, A. C. Luchiari, C. Silva, E. D. Maffei, Francisco Humberto de Abreu [UNESP] Chudzinski-Tavassi, A. M. |
author2_role |
author author author author author author author author |
dc.contributor.none.fl_str_mv |
Instituto Butantan CET Hosp Sirio Libanes Universidade Estadual Paulista (Unesp) Hosp Santa Catarina |
dc.contributor.author.fl_str_mv |
Andrade, S. A. Carrijo-Carvalho, L. C. Peceguini, L. A. M. Wlian, L. Sato, A. C. Luchiari, C. Silva, E. D. Maffei, Francisco Humberto de Abreu [UNESP] Chudzinski-Tavassi, A. M. |
dc.subject.por.fl_str_mv |
Prothrombin activation Procoagulant Exogenous hemostatic factor rLopap Bleeding Anticoagulant |
topic |
Prothrombin activation Procoagulant Exogenous hemostatic factor rLopap Bleeding Anticoagulant |
description |
Lopap, found in the bristles of Lonomia obliqua caterpillar, is the first exogenous prothrombin activator that shows serine protease-like activity, independent of prothrombinase components and unique lipocalin reported to interfere with hemostasis mechanisms. To assess the action of an exogenous prothrombin activator reversing the anticoagulant and antihemostatic effect induced by low molecular weight heparin (LMWH), male New Zealand rabbits (N = 20, weighing 3.8-4.0 kg) allocated to 4 groups were anticoagulated with 1800 IU/kg LMWH (iv) over 2 min, followed by iv administration of saline or recombinant Lopap (rLopap) at 1 mu g/kg (LG1) or 10 mu g/kg (LG10), 10 min after the injection of LMWH, in a blind manner. Control animals were treated only with saline. The action of rLopap was assessed in terms of activated partial thromboplastin time (aPTT), prothrombin fragment F1+2, fibrinogen, and ear puncture bleeding time (BT) at 5, 10, 15, 17, 20, 30, 40, 60, and 90 min after initiation of LMWH infusion. LG10 animals showed a decrease of aPTT in more than 50% and BT near to normal baseline. The level of prothrombin fragment F1+2 measured by ELISA had a 6-fold increase with rLopap treatment (10 mu g/kg) and was inversely proportional to BT in LMWH-treated animals. Thus, Lopap, obtained in recombinant form using E. coli expression system, was useful in antagonizing the effect of LMWH through direct prothrombin activation, which can be a possible strategy for the reversal of bleeding and anticoagulant events. |
publishDate |
2012 |
dc.date.none.fl_str_mv |
2012-10-01 2014-05-20T15:31:28Z 2014-05-20T15:31:28Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1590/S0100-879X2012007500108 Brazilian Journal of Medical and Biological Research. São Paulo: Assoc Bras Divulg Cientifica, v. 45, n. 10, p. 929-934, 2012. 0100-879X http://hdl.handle.net/11449/40593 10.1590/S0100-879X2012007500108 S0100-879X2012007500108 WOS:000308408600007 |
url |
http://dx.doi.org/10.1590/S0100-879X2012007500108 http://hdl.handle.net/11449/40593 |
identifier_str_mv |
Brazilian Journal of Medical and Biological Research. São Paulo: Assoc Bras Divulg Cientifica, v. 45, n. 10, p. 929-934, 2012. 0100-879X 10.1590/S0100-879X2012007500108 S0100-879X2012007500108 WOS:000308408600007 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Brazilian Journal of Medical and Biological Research 1.492 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
929-934 |
dc.publisher.none.fl_str_mv |
Associação Brasileira de Divulgação Científica (ABRADIC) |
publisher.none.fl_str_mv |
Associação Brasileira de Divulgação Científica (ABRADIC) |
dc.source.none.fl_str_mv |
Web of Science reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
_version_ |
1797789627989360640 |