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The Reversal of the Anticoagulant and Anti‐hemostatic Effect of LMWH by rLopap
Author(s) -
Andrade Sonia,
CarrijoCarvalho Linda,
Sato Ana,
Abreu Maffei Francisco,
ChudzinskiTavassi Ana
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.565.11
Subject(s) - hemostasis , partial thromboplastin time , anesthesia , saline , medicine , prothrombin time , thrombin , thromboplastin , bleeding time , pharmacology , antithrombin , thrombin time , anticoagulant , coagulation , chemistry , heparin , platelet , platelet aggregation
Lopap, found in the bristles of the caterpillar Lonomia obliqua, is the first exogenous prothrombin activator that shows serineprotease‐like activity and only lipocalin reported to interfere with hemostasis mechanisms. The aim was to assess the effect of recombinant Lopap, obtained using an E. coli expression system, as an exogenous hemostatic factor in reversing bleeding induced by LMWH .The experimental protocol was approved by the Ethics Committee for the Use of Animals of the Teaching and Research Institute, Hospital Sírio‐Libanês. Briefly, anesthesia was induced with ketamine HCl (40 mg/kg, im) and xylazine (5 mg/kg, im) and was maintained by intermittent injections of the same mixture. Rabbits were allocated to 4 groups and received 1800IU/kg LMWH iv over 2 min, followed by iv administration of saline (SG) or rLopap at a dose of 1 μg/kg (LG1) or 10 μg/kg (LG10), 10 min after the injection of LMWH. The reversal of the anticoagulant and anti‐hemostatic effect of LMWH by rLopap were assessed in terms of bleeding time (BT) and laboratory tests; activated partial thromboplastin time (aPTT), prothrombin time (TP), prothrombin fragment F1+2, Thrombin generation, Thrombin‐Antithrombin complex (TAT) and fibrinogen. LG10 animals showed a decreased BT near normal baseline. The levels of prothrombin fragment F1+2 and measured thrombin were inversely proportional to BT. rLopap can be a possible template for the reversal of bleeding and anticoagulant events. Supported by FAPESP