J Thorac Cardiovasc Surg 2003;126:2112-2113
© 2003 The American Association for Thoracic Surgery
Activated prothrombin complex concentrates and recombinant factor VIIa in the bleeding patient: are they appropriate and safe?
Louis M. Aledort, MD
The Mary Weinfeld Professor of Clinical Research in Hemophilia, Mount Sinai School of Medicine, New York, NY 10029, USA
To the Editor:
I read with great interest the article of Bui and colleagues,1 "Fatal Thrombosis After Administration of Activated Prothrombin Complex Concentrates in a Patient Supported by Extracorporeal Membrane Oxygenation Who Had Received Activated Recombinant Factor VII," in the October 2002 Journal. Many issues related to the administration of activated prothrombin complex concentrates presented by this case were too simply discussed.
First, the patient had evidence of disseminated intravascular coagulation both before the cessation of heparin and after its discontinuation, with prolonged prothrombin time and partial thromboplastin time. No data are available regarding the patient's platelet count before or after surgical intervention. Both recombinant factor VIIa and factor VIII bypassing activity (FEIBA) were used off-label, about which the authors made little comment. Cardiac surgery with extracorporeal membrane oxygenation is known to activate clotting, and death might well have occurred even without either biologic agent. The cardiac death may not have been from thrombus, but of another origin; because no autopsy was performed, however, all this is pure speculation.
The authors stated with great conviction that thrombosis with recombinant factor VIIa is less common than with FEIBA. Continued hemorrhage itself is a cause of activation of coagulation. Agents known to aid in stopping hemorrhage in patients with coagulation defects have caused thrombotic episodes.
Almost all the life-threatening thrombotic events with FEIBA have occurred with doses exceeding those recommended.2 Bui and colleagues1 provided no data regarding the dose of FEIBA given. Thrombotic events, including myocardial infarctions, have also been reported for recombinant factor VIIa.3 The relative risks of these two biologic agents are unknown; there are no prospective comparative data available to make such a determination. The cumulative clinical anecdotal data for recombinant factor VIIa are from a much briefer span than those for FEIBA.
Case reports can at times be important for recognition of new diseases and during postlicensing surveillance for adverse events. Recently, a report has demonstrated that the combination of recombinant factor VIIa and FEIBA may, if anything, be additive without increasing adverse responses.4,5
I caution the authors that conclusions presented with inadequate data may well lead readers to incorrect interpretations of the events described.
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References
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- Bui JD, Despotis GD, Trulock EP, Patterson GA, Goodnough LT. Fatal thrombosis after administration of activated prothrombin complex concentrates in a patient supported by extracorporeal membrane oxygenation who had received activated recombinant factor VII. J Thorac Cardiovasc Surg. 2002;124:852–854[Free Full Text]
- Ehrlich HJ, Henzl MJ, Gomperts ED. Safety of factor VIII inhibitor bypass activity (FEIBA): 10-year compilation of thrombotic adverse events. Haemophilia. 2002;8:83–90[Medline]
- Aledort LM. rVIIa—its thrombogenicity. [letter]Thromb Haemost. 2000;84:522–523[Medline]
- Schneiderman J, Nugent DJ, Young G. Combination therapy with activated prothrombin complex concentrate (APCC) and recombinant factor VIIa (rFVIIa) in patients with severe hemophilia and inhibitors. Blood. 2002;100:696a
- Key NS, Christie B, Henderson N, Nelsestuen GL. Possible synergy between recombinant factor VIIa and prothrombin complex concentrate in hemophilia therapy. Thromb Haemost. 2002;88:60–65[Medline]
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