Ann Thorac Surg 2007;83:355
© 2007 The Society of Thoracic Surgeons
Correspondence
Caution With the Use of Recombinant Activated Factor VII in Treating Postoperative Hemorrhage in Cardiac Surgery
Sharif Al-Ruzzeh, PhD, FRCS,
Amr Mahmoud, MS, FCARCSI,
Samir Shah, MS, FRCS,
David O’Regan, MD, FRCS
The Yorkshire Heart Centre, Leeds General Infirmary, Great George Street, Leeds, LS1 3EX United Kingdom
(Email: sharifalruzzeh{at}hotmail.com).
To the Editor:
We congratulate Bishop and colleagues [1] for investigating the use of recombinant factor VIIa (rFVIIa) as a "rescue therapy for uncontrollable postoperative haemorrhage after cardiac surgery," which is a challenging and potentially life-threatening complication. However we would like to raise the following 3 issues:
- 1 Since the Food and Drug Administration (FDA) first licensed rFVIIa, in 1999 for use in patients with hemophilia, its use has been expanded to include bleeding in nonhemophilia patients, but without a clear consensus on the clinical indications [2]. Furthermore, concerns have been raised about its safety and efficacy in the latter group of patients with several reported cases of thromboembolic adverse events in the literature [2]. These include cerebrovascular accidents, myocardial infarction, peripheral arterial thrombosis, pulmonary embolism, and deep venous thrombosis. There is also evidence in the literature that such adverse events due to "off-label" use of rFVIIa are underreported [2]. A recently published systematic review of literature about pharmacologic uses of rFVIIa identified 28 clinical trials in addition to about 300 case series and reports. It demonstrated that the use of rFVIIa was safe and effective in more than 90% of patients with hemophilia and other coagulation disorders. However the authors stated that there was not enough evidence to support the use of rFVIIa in patients without pre-existing coagulation disorder presenting with severe bleeding with or without surgery [3].
- 2 The cause and effect relationship is not clear in the study [1]. The pre-rFVIIa coagulation screen was performed between the first cycle and the second cycle of non-red cell blood product support according to the management protocol of the cases reported. However, the post-rFVIIa coagulation screen was performed after both the second cycle of non-red cell blood product support and rFVIIa had been given. It is our contention that before any conclusions can be made about the cause and effect relationship between rFVIIa and the control of postoperative bleeding in this study, there should have been a control group consisting of patients who had been administered a second cycle of non-red cell blood product support, but without rFVIIa for comparison.
- 3 A particularly important safety concern with the use of rFVIIa in cardiac surgery is the potential for inappropriate clotting [4]. After cardiac surgery with cardiopulmonary bypass, there is upregulation of tissue factor expression both locally in areas of tissue injury as well as systemically [5, 6]. Given that the mechanism of action for rFVIIa involves binding to tissue factor [7], therefore increased tissue factor expression may lead to more systemic clot formation [4]. Furthermore, many cardiac surgery patients have vulnerable atherosclerotic plaques in their coronary vasculature; therefore excessive thrombin generation by rFVIIa may increase the incidence of acute coronary syndromes during the perioperative period [4].
We believe that a degree of caution should be applied regarding the use of rFVIIa in the control of excessive surgical bleeding after cardiac surgery, particularly in absence of both clear guidelines and evidence from clinical randomized trials.
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References
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- Bishop C, Renwick W, Hogan C, Haeusler M, Tuckfield A, Tatoulis J. Recombinant activated factor VII: treating postoperative hemorrhage in cardiac surgery Ann Thorac Surg 2006;81:875-879.[Abstract/Free Full Text]
- O’Connell K, Wood J, Wise R, Lozier J, Braun M. Thromboembolic adverse events after use of recombinant human coagulation factor VIIa JAMA 2006;295:293-298.[Abstract/Free Full Text]
- Levi M, Peters M, Buller H. Efficacy and safety of recombinant factor VIIa for treatment of severe bleeding: a systematic review Crit Care Med 2005;33:883-890.[Medline]
- Dietrich W, Spannagl M. Caveat against the use of activated recombinant factor VII for intractable bleeding in cardiac surgery Anesth Analg 2002;94:1369-1370.[Free Full Text]
- Ernofsson M, Thelin S, Siegbahn A. Monocyte tissue factor expression, cell activation, and thrombin formation during cardiopulmonary bypass: a clinical study J Thorac Cardiovasc Surg 1997;113:576-584.[Abstract/Free Full Text]
- Chung J, Gikakis N, Rao A, Drake T, Colman R, Edmunds L. Pericardial blood activates the extrinsic coagulation pathway during clinical cardiopulmonary bypass Circulation 1996;93:2014-2018.[Abstract/Free Full Text]
- Hoffman M, Monroe D, Roberts H. Activated factor VII activates factors IX and X on the surface of the activated platelets: thoughts on the mechanism of action of high-dose activated factor VII Blood Coag Fibrinol 1998;9(Suppl 1):S61-S65.[Medline]
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Ann. Thorac. Surg. 83: 355-356.
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Ann. Thorac. Surg.,
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355 - 356.
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