Heparinless cardiopulmonary bypass with active-site blocked factor IXa

A preliminary study on the dog

T. B. Spanier, M. C. Oz, O. P. Minanov, R. Simantov, W. Kisiel, David Stern, E. A. Rose, A. M. Schmidt

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Objective: Cardiopulmonary bypass is a potent stimulus for activation of procoagulant pathways. Heparin, the traditional antithrombotic agent, however, is often associated with increased perioperative blood loss because of its multiple sites of action in the coagulation cascade and its antiplatelet and profibrinolytic effects. Furthermore, heparin-mediated immunologic reactions (that is, heparin-induced thrombocytopenia) may contraindicate its use. Cardiopulmonary bypass with a selective factor IXa inhibitor was tested to see whether it could effectively limit bypass circuit/intravascular space thrombosis while decreasing extravascular bleeding, thereby providing an alternative anticoagulant strategy when heparin may not be safely administered. Methods: Active site-blocked factor IXa, a competitive inhibitor of the assembly of factor IXa into the factor X activation complex, was prepared by modification of the enzyme's active site by the use of dansyl glutamic acid-glycinearginine-chlormethylketone. Twenty mongrel dogs (five were given standard heparin/protamine; 15 were given activated site-blocked factor IXa doses ranging from 300 to 600 μ/kg) underwent 1 hour of hypothermic cardiopulmonary bypass, and blood loss was monitored for 3 hours after the procedure. Results: Use of activated site- blocked factor IXa as an anticoagulant in cardiopulmonary bypass limited fibrin deposition within the extracorporeal circuit as assessed by scanning electron microscopy, comparable with the antithrombotic effect seen with heparin. In contrast to heparin, effective antithrombotic doses of activated site-blocked factor IXa significantly diminished blood loss in the thoracic cavity and in an abdominal incisional bleeding model. Conclusion: These initial studies on the dog suggest that administration of activated site- blocked factor IXa may be an effective alternative anticoagulant strategy in cardiopulmonary bypass when heparin is contraindicated, affording inhibition of intravascular/extracorporeal circuit thrombosis with enhanced hemostasis in the surgical wound.

Original languageEnglish (US)
Pages (from-to)1179-1188
Number of pages10
JournalJournal of Thoracic and Cardiovascular Surgery
Volume115
Issue number5
DOIs
StatePublished - Jan 1 1998
Externally publishedYes

Fingerprint

Factor IXa
Cardiopulmonary Bypass
Heparin
Catalytic Domain
Dogs
Anticoagulants
Thrombosis
Hemorrhage
Thoracic Cavity
Factor X
Protamines
Fibrinolytic Agents
Hemostasis
Fibrin
Thrombocytopenia
Electron Scanning Microscopy
Glutamic Acid

All Science Journal Classification (ASJC) codes

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine

Cite this

Heparinless cardiopulmonary bypass with active-site blocked factor IXa : A preliminary study on the dog. / Spanier, T. B.; Oz, M. C.; Minanov, O. P.; Simantov, R.; Kisiel, W.; Stern, David; Rose, E. A.; Schmidt, A. M.

In: Journal of Thoracic and Cardiovascular Surgery, Vol. 115, No. 5, 01.01.1998, p. 1179-1188.

Research output: Contribution to journalArticle

Spanier, T. B. ; Oz, M. C. ; Minanov, O. P. ; Simantov, R. ; Kisiel, W. ; Stern, David ; Rose, E. A. ; Schmidt, A. M. / Heparinless cardiopulmonary bypass with active-site blocked factor IXa : A preliminary study on the dog. In: Journal of Thoracic and Cardiovascular Surgery. 1998 ; Vol. 115, No. 5. pp. 1179-1188.
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T1 - Heparinless cardiopulmonary bypass with active-site blocked factor IXa

T2 - A preliminary study on the dog

AU - Spanier, T. B.

AU - Oz, M. C.

AU - Minanov, O. P.

AU - Simantov, R.

AU - Kisiel, W.

AU - Stern, David

AU - Rose, E. A.

AU - Schmidt, A. M.

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