Thrombophilia Due to Factor V and Factor II Mutations and Formation of a Dural Arteriovenous Fistula: Case Report and Review of a Rare Entity

Abstract

Genetic mutations underlying thrombophilia are often recognized in patients with thromboembolic episodes. However, the clinical and therapeutic implications of such findings often remain unclear. We report the first case of a dural arteriovenous fistula (DAVF) in a patient with a combined factor II and factor V Leiden mutation. A 40-year-old man presented with a large left temporal and intraventricular hemorrhage. An initial angiogram showed thrombosis of the left sigmoid sinus but no evidence of a vascular malformation. One year after the hemorrhage, an angiographic study showed the appearance of a right DAVF. During the follow-up period, the patient was found to harbor heterozygosity for a mutation of factor V and a mutation of factor II. Recognition of the patient's thrombophilia led to prolonged oral anticoagulation therapy to reduce the risk of a recurrent thrombotic episode. Despite the increased risk of bleeding, the therapy was considered justified. DAVFs may occur after sinus thrombosis in patients with combined factor II and factor V mutations. This observation indicates the association of multiple hematological disorders with DAVFs in individual patients. Moreover, it raises the clinical conundrum of how to manage patients with thrombophilia, intracranial hemorrhage, and DAVFs.

Keywords: Factor V Leiden mutation; G20210A mutation; anticoagulation; arteriovenous malformation; hypercoagulable state.

Figure 1

(A) Preoperative computed tomographic image shows the left intracerebral and intraventricular hemorrhage. (B) Preoperative angiogram shows thrombosis of the left sigmoid sinus. However, the lateral projections of (C) the posterior circulation and (D) the left external carotid angiogram show no DAVF. Control angiograms 1 year after treatment show (F) partial patency of the left sigmoid sinus and (E,G,H) the formation of a DAVF between tentorial branches of the (E) left external carotid artery, (G) right vertebral artery, and (H) meningeal branches of the external carotid artery to (E) the right transverse sinus and confluens (arrow).

Figure 2

The flowchart shows the mechanism proposed to underlie the development of the patient's complex clinical picture. The genetic process begins with the mutation that caused the thrombosis and hemorrhage (1). Increased venous pressure (2) leads to the DAVF (3). Treatment with anticoagulation is a dilemma because of its beneficial effects on thromboembolic events and its adverse effects on hemorrhage. The dotted lines indicate the possible positive effects on recanalization of the thrombosed sinus but the increased risk of hemorrhage and development of the DAVF. (With permission from Barrow Neurological Institute.)

Figure 3

Schematic representation of a proposed mechanism that explains the appearance of the fistula and its implications for management. (1) Sinus occlusion was associated with increased venous pressure (2) and intracerebral hemorrhage. (3) Appearance of the DAVF. The numbers correspond to the numbers in Fig. 2. (With permission from Barrow Neurological Institute.)