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Inactivated antithombin as anticoagulant reversal in a rat model of cardiopulmonary bypass: a potent and potentially safer alternative to protamine
- Source :
- British Journal of Haematology, British Journal of Haematology, Wiley, 2018, 180 (5), pp.715-720. ⟨10.1111/bjh.15091⟩, British Journal of Haematology, 2018, 180 (5), pp.715-720. ⟨10.1111/bjh.15091⟩
- Publication Year :
- 2018
- Publisher :
- HAL CCSD, 2018.
-
Abstract
- International audience; Heparin anticoagulation followed by protamine reversal is commonly used in cardiopulmonary bypass (CPB). As an alternative to protamine, a recombinant inactive antithrombin (riAT) was designed as an antidote to heparin and was previously shown to be as potent as protamine in-vitro. In the present study, riAT was assessed for its ability to neutralize heparin after CPB in a rat model. After 60 min of CPB under heparin, rats received 5 mg/kg protamine, 37.5 mg/kg riAT or phosphate buffered saline (PBS) as placebo. Residual anticoagulant activity was assessed using the activated partial thromboplastin time assay before, and 10-30 min after reversion. Haemodynamic monitoring was performed and plasma histamine concentration was also measured. In this model, riAT appeared to be as efficient as protamine in neutralizing heparin. Ten minutes after injection, riAT and protamine both decreased heparin activity, to 1.8 AE 1.3 and 4.5 AE 1.4 u/ ml, respectively (23.1 AE 5.1 u/ml in placebo group). Furthermore, evolution of mean carotid arterial pressure, heart rate and plasma histamine levels was comparable in rats treated with PBS or riAT, while protamine exhibited haemodynamic side effects and increased histamine plasma concentration. Thus, riAT could represent an advantage over protamine in CPB because it efficiently reverses heparin activity without negative effects on haemodynamic parameters and plasma histamine level.
- Subjects :
- Male
0301 basic medicine
[SDV.BIO]Life Sciences [q-bio]/Biotechnology
[SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO]
medicine.medical_treatment
030204 cardiovascular system & hematology
Pharmacology
heparin
law.invention
chemistry.chemical_compound
0302 clinical medicine
law
Protamines
Antidote
biology
medicine.diagnostic_test
Anticoagulant
Antithrombin
Heparin Antagonists
Hematology
Heparin
[SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences
[SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system
3. Good health
[SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences
antithrombin
[SDV.IMM]Life Sciences [q-bio]/Immunology
cardiopulmonary bypass
protamine
Histamine
medicine.drug
Partial thromboplastin time
[SDV.IMM] Life Sciences [q-bio]/Immunology
medicine.drug_class
Antithrombins
03 medical and health sciences
[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system
medicine
Cardiopulmonary bypass
[SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO]
Animals
Rats, Wistar
Hemodynamics
Anticoagulants
Protamine
[SDV.BIO] Life Sciences [q-bio]/Biotechnology
030104 developmental biology
chemistry
biology.protein
antidote
Subjects
Details
- Language :
- English
- ISSN :
- 00071048 and 13652141
- Database :
- OpenAIRE
- Journal :
- British Journal of Haematology, British Journal of Haematology, Wiley, 2018, 180 (5), pp.715-720. ⟨10.1111/bjh.15091⟩, British Journal of Haematology, 2018, 180 (5), pp.715-720. ⟨10.1111/bjh.15091⟩
- Accession number :
- edsair.doi.dedup.....0842c250ae2e982810f279eafaeb9093