Enhanced Thrombogenesis is Physiologic After Transcatheter Closure of Patent Foramen Ovale
To the Editor:
We read with interest the article by Bédard et al1 on the enhanced thrombogenesis associated with transcatheter closure of patent foramen ovale (PFO). Through an accurate and sophisticated analysis, the authors showed that transcatheter PFO closure is associated with an increased activation of the coagulation system with no change in platelet activation. The coagulation cascade seemed to be fairly activated as early as 1 week after the procedure and returned to normal values within 3 months from the procedure. The authors proposed that enhanced thrombin generation observed soon after the procedure is most likely related to the deposit of fibrin at the interface between blood and the device. Based on this assumption, the authors conclude that: (1) stroke recurrence might be related to device-induced thrombogenesis; and (2) anticoagulation should be preferred to antiplatelet drugs for the first 3 months after the procedure to reduce the risk of early stroke recurrence. However, despite an impressive increase in the pro-coagulant activity, the authors could not detect any thrombus on the device, and because of the sample size and follow-up length they could not report any recurrence of cerebral ischemia.1 Opposite to what might have been expected, the authors could not observe any relation between device size and amount of thrombin activation. A wider device surface would be expected to produce a higher thrombin generation, especially because it has been clinically associated with a higher prevalence of left-side disk thrombosis.2 Despite the elegant data presentation, we think that the impact of the present study is limited. The authors have to be reminded that, as reported in 1997 by the inventor of the Amplatzer device,3 the Amplatzer PFO occlusion system, as well as the atrial septal defect occlusion system, “is filled with fluffy Dacron threads that have high thrombogenicity, to achieve rapid closure of the defect.” The presence of a polyester mesh inside the waist of the device is the main mechanism promoting intra-device thrombus formation and shunt abolishment. Therefore, activation of the coagulation system is an essential component of the sealing properties of this device. We think that rather than showing an abnormal phenomenon, the aforementioned study1 beautifully depicts a physiological picture intrinsically related and connatural to the procedure.
Despite all this, the issue of medical therapy after PFO closure remains crucial, especially in the relatively frequent setting of a patient with thrombophilia. We previously suggested the use of oral anticoagulation in patients with thrombophilia,4 even if no evidence exists to date to support this approach.
Because no argument was provided to suggest that activation of the coagulation after PFO closure might be clinically relevant, we encourage the authors to test their findings in a larger cohort of patients and assess whether an abnormal activation of the coagulation system could be associated with clinical end-points like postprocedural recurrence of cerebral ischemia or migraine, or at least thrombus formation on the device.
Bédard E, Rodes-Cabau J, Houde C, Mackey A, Rivest D, Cloutier S, Noel M, Marrero A, Cote JM, Chetaille P, Delisle G, Leblanc MH, Bertrand OF. Enhanced thrombogenesis but not platelet activation is associated with transcatheter closure of patent foramen ovale in atients with cryptogenic stroke. Stroke. 2007; 38: 100–104.
Sharafuddin MJ, Gu X, Titus JL, Urness M, Cervera-Ceballos JJ, Amplatz K. Transvenous closure of secundum atrial septal defects: preliminary results with a new self-expanding nitinol prosthesis in a swine model. Circulation. 1997; 95: 2162–2168.
Giardini A, Donti A, Formigari R, Bronzetti G, Prandstraller D, Bonvicini M, Palareti G, Guidetti D, Gaddi O, Picchio FM. Comparison of results of percutaneous closure of patent foramen ovale for paradoxical embolism in patients with versus without thrombophilia. Am J Cardiol. 2004; 94: 1012–1016.