Factor V Leiden and prothrombin gene mutation may predispose to paradoxical embolism in subjects with patent foramen ovale

Abstract

The role of paradoxical embolism through patent foramen ovale as a mechanism of cryptogenic stroke is controversial. If a venous source of emboli is relevant, prothrombotic states should be associated with patent foramen ovale and cryptogenic stroke. We assessed the occurrence of several prothrombotic states (factor V Leiden, prothrombin G20210A, deficiencies in protein S, protein C and antithrombin, lupus anticoagulant, anticardiolipin antibodies, elevated factor VIII, resistance to activated protein C) and classical risk factors for venous thrombosis in 57 adult patients with cryptogenic stroke and patent foramen ovale and in 104 matched controls. Prothrombotic states [odds ratio (OR) 2.8; 95% confidence interval (CI), 1.2-6.5; P = 0.021], migraine with aura (OR 4.4; 95% CI 1.8-10.8; P = 0.001) and classical risk factors for venous thrombosis (OR 2.5; 95% CI 1.1-5.7; P = 0.037) were independent risk factors for cryptogenic stroke. In particular factor V Leiden or prothrombin G20210A associated with cryptogenic stroke (P = 0.022) whereas other coagulation abnormalities did not (P = 0.140). Among the patients with prothrombotic states, Valsalva manoeuvre was common at onset of stroke. Our results support the possibility of paradoxical embolism behind strokes in patients with patent foramen ovale.

Forame oval patente e acidente vascular cerebral isquêmico em jovens: associação causal ou estatística?

“…In this scenario we reestablish the well accepted causality criteria 7,20 and emphasize the evidences available in the literature about a possible association between PFO and IS. Therefore, we prepared Table 4 where we try to answer the nine causality criteria in the present context.…”

“…In the context of the current analysis we only evaluated venous thrombophilias, since they could be potentially related with paradoxical embolism. Although there is evidence of the association between mutation of the prothrombin gene (venous thrombophilia) and cryptogenic IS 19,20 , this measurement was not available to us at that time. Out of 26 patients with venous thrombophilia, the great majority (21 cases or 81%) was caused by protein S deficiency.…”

Epidemiology of Myocardial Infarction Caused by Presumed Paradoxical Embolism via a Patent Foramen Ovale

“…Vice versa MI with normal coronaries has been reported in [1][2][3][4][5][6][7][8] 46 We did not follow up the patients in our series who were not found to have a PFO.…”

Right-to-left shunt and the hypercoagulable state: does paradoxical embolism play a role in patients with antiphospholipid syndrome and stroke?

“…PFO can be associated with cryptogenic stroke; the mechanism is postulated to be a PE, where clots originate in the venous circulation and travel to the arterial side through an RLS 10,11 . Systemic hypercoagulable states can potentially increase clot formation 12 .…”