Enhanced Thrombogenesis but Not Platelet Activation Is Associated With Transcatheter Closure of Patent Foramen Ovale in Patients With Cryptogenic Stroke

Abstract

Background and Purpose-No studies have yet determined whether antiplatelet or anticoagulant therapy is the more appropriate treatment after transcatheter closure of patent foramen ovale (PFO) in patients with cryptogenic stroke. The objective of this study was to prospectively evaluate the presence, degree, and timing of activation of the platelet and coagulation systems after transcatheter closure of PFO in patients with cryptogenic stroke. Methods-Twenty-four consecutive patients (mean age, 44Ϯ10 years; 11 men) with previous cryptogenic stroke who had undergone successful transcatheter closure of PFO were included in the study. Prothrombin fragment 1ϩ2 (F1ϩ2) and thrombin-antithrombin III (TAT) were used as markers of coagulation activation, and soluble P-selectin and soluble CD40 ligand were used as markers of platelet activation. Measurements of all hemostatic markers were taken at baseline just before the procedure and at 7, 30, and 90 days after device implantation. Results-F1ϩ2 and TAT levels increased from 0.41Ϯ0.16 nmol/L and 2.34Ϯ1.81 ng/mL, respectively, at baseline to a maximal value of 0.61Ϯ0.16 nmol/L and 4.34Ϯ1.83 ng/mL, respectively, at 7 days, gradually returning to baseline levels at 90 days (PϽ0.001 for both markers). F1ϩ2 and TAT levels at 7 days after PFO closure were higher than those obtained in a group of 25 healthy controls (PϽ0.001 for both markers). Levels of soluble P-selectin and soluble CD40 ligand did not change at any time after PFO closure. Conclusions-Transcatheter closure of PFO is associated with significant activation of the coagulation system, with no increase in platelet activation markers. These findings raise the question of whether optimal antithrombotic treatment after PFO closure should be short-term anticoagulant rather than antiplatelet therapy.

Altered Fibrin Clot Structure/Function in Patients With Cryptogenic Ischemic Stroke

“…3,9 Alterations in fibrin function/structure in stroke patients with PFO cannot be attributed to the activation of coagulation observed shortly after PFO closure. 11 Higher clot permeability and faster lysis in stroke patients with PFO than in those without PFO is likely explained by lower proportion of smokers in the former group. Smoking is known to unfavorably alter clot properties.…”

Atherosclerotic Burden Findings in Young Cryptogenic Stroke Patients With and Without a Patent Foramen Ovale

“…The degree of right-to-left shunt was considered small if Ͻ20 microbubbles appeared and large if Ն20 microbubbles appeared. 17,18 Atrial septal aneurysm (ASA) was diagnosed when the atrial septum exhibited an excursion into the left or right atrium Ն11 mm or a total excursion Ն15 mm and the base of the aneurysmal septum was at least of 15 mm in diameter. 19 Traditional cardiovascular risk factors were systematically recorded in all patients and included smoking status, history of hypertension defined as blood pressure Ն140/90 mm Hg or treatment with antihypertensive medication, history of dyslipidemia defined as low-density cholesterol levels Ͼ3.50 mmol/L or treatment with lipid-lowering medication, and history of diabetes defined as serum fasten blood sugar Ͼ6.9 mmol/L or treatment with oral hypoglycemic agents or insulin.…”

Response to Letter by Giardini and Donti

“…1 As a preliminary step toward determining the optimal type and timing of antithrombotic therapy for such patients, our mechanistic study evaluated the hemostatic effects of the implantation of a PFO closure device at the atrial level, and showed that transient enhanced activation of the coagulation system was the main effect associated with the procedure, with no detectable effect on platelet activation. 2 While our results provide a mechanistic rationale for short-term anticoagulation in such cases we never stated that on the basis of these results anticoagulant therapy must henceforth be established as the antithrombotic treatment after PFO closure. As emphasized throughout the article, our results reinforce the importance of performing out prospective and adequately powered randomized trials to determine the most appropriate and cost-effective antithrombotic therapy after PFO closure.…”

“…In fact, half of the patients included in our study exhibited an activation of the coagulation system above the upper normal limits 1 week after PFO closure and in 15% of them the markers of coagulation activation remained abnormally high 1 month after device implantation. 2 Cases of device thrombosis have been reported for all types of commercially available PFO closure devices, including the Amplatzer PFO device, clearly suggesting that the process of "physiological device thrombosis" can become exacerbated and pathological in some cases. 3,4 Thus, it seems appropriate to control the PFO closure device thrombotic process with some kind of antithrombotic therapy, at least up to the completion of device endothelialization.…”