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Editor,—Elford and colleagues recently described rapid and spectacular thrombotic occlusion of an iatrogenic axillary artery pseudoaneurysm following injection of thrombin.1 The authors concluded that this treatment is “safe” and that it should be considered as the treatment of choice for iatrogenic pseudoaneurysm. Although we agree that thrombin injection is promising, there are important safety issues to address before this treatment can be adopted routinely.
There are little safety data on the immunological effects of these products. Fibrinogen/thrombin products are widely used to help achieve haemostasis during complex cardiac surgery. A recent study of 21 patients undergoing cardiothoracic surgery with fibrin glue (bovine fibrinogen clotted with bovine thrombin) demonstrated IgM and IgG antibodies to bovine thrombin, fibrinogen and factor V in every patient.2 Although there were no bleeding complications reported in this study, these antibodies can cross react with their human counterparts and result in severe haemorrhagic complications.3 Antibodies have also been detected after administration of topical bovine thrombin during dental procedures.4 As direct intravascular injection may result in a more intense immunological and haemostatic response, caution appears to be appropriate until immunologically compatible human thrombin is routinely available.
Many pseudoaneurysms occur after coronary interventional procedures and optimal timing of thrombin treatment has yet to be determined. Thrombotic complications following administration of intravascular bovine thrombin have been described5 which may have resulted from leakage of thrombin from the pseudoaneurysm into the systemic circulation, although other mechanisms are also possible.5 Circulating thrombin should rapidly be diluted or neutralised by thrombomodulin and antithrombin III, but potentially catastrophic exposure of the coronary lesion to activated thrombin may be possible. Some pseudoaneurysms may resolve spontaneously after discontinuation of systemic anticoagulation, despite oral antiplatelet agents. Therefore our practice is to use thrombin injection for femoral pseudoaneurysm resistant to ultrasound guided compression, and treatment is deferred until 48 hours after intervention.
We conclude that thrombin injection using ultrasound guidance is poised to replace surgical exploration as the second line treatment for iatrogenic pseudoaneurysm but, particularly for femoral pseudoaneurysm after coronary intervention, further data are necessary before ultrasound guided compression can be abandoned.
This letter was shown to the authors who reply as follows:
While we agree that the intravascular use of thrombosis inducing agents is relatively recent, all of the cases to which Ferguson and Banning refer1–3 involved the use of bovine thrombin. The Tisseel Kit (Immuno Ag, Vienna) consists of Tisseel, a sealer protein concentrate containing bovine aprotinin, together with human thrombin and calcium chloride solution. We reconstitute the human thrombin using the calcium chloride solution, and inject this. We do not use the sealer protein concentrate, relying instead on the patient's own coagulation factors to form a clot. The manufacturers of the Tisseel Kit confirm that there is, therefore, no risk of antibodies to bovine proteins being formed.
The authors also raise concerns about thrombotic complications that may have resulted from leakage of thrombin out of a pseudoaneurysm into the systemic circulation.1-4 The case to which they refer, described in our case report, is unusual in that the neck of the pseudoaneurysm (arising from the brachial artery in a child) was of similar diameter to that of the vessel. This is why we advise that it is essential to assess the diameter and length of the pseudoaneurysm neck before thrombin injection. We recommend that, should the neck be anything other than a pinpoint source, then balloon occlusion should be considered.