Testing for Inherited Thrombophilias in Arterial Stroke Can It Cause More Harm Than Good?

• Published in: Stroke (1970) 2010-12, Vol.41 (12), p.2985-2990
• Main Authors: MORRIS, Jane G, SINGH, Swaraj, FISHER, Marc
• Format: Article
• Language: English
• Subjects: Antithrombin III Deficiency - genetics; Antithrombin III Deficiency - pathology; Biological and medical sciences; Brain Ischemia - complications; Brain Ischemia - diagnosis; Brain Ischemia - genetics; Case-Control Studies; Cost-Benefit Analysis; Factor V Deficiency - genetics; Factor V Deficiency - pathology; Foramen Ovale, Patent - complications; Foramen Ovale, Patent - pathology; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Humans; Medical sciences; Nervous system (semeiology, syndromes); Neurology; Protein C Deficiency - genetics; Protein C Deficiency - pathology; Protein S Deficiency - genetics; Protein S Deficiency - pathology; Stroke - complications; Stroke - diagnosis; Stroke - genetics; Thrombophilia - complications; Thrombophilia - diagnosis; Thrombophilia - genetics; Vascular diseases and vascular malformations of the nervous system
• ISSN: 0039-2499; 1524-4628; 1524-4628
• DOI: 10.1161/STROKEAHA.110.595199

Despite a paucity of evidence supporting a true association of ischemic stroke and the inherited thrombophilias, it is common practice for many neurologists to order these tests as part of the work-up of ischemic stroke, especially in young patients. Treatment with oral anticoagulation is often used in patients with positive results for the inherited thrombophilias. We reviewed the literature focusing on case-control studies of the 5 most commonly inherited disorders of coagulation: protein C deficiency, protein S deficiency, antithrombin deficiency, and the factor V Leiden and prothrombin gene mutations in patients with stroke. We also analyzed the available data on stroke patients with inherited thrombophilia and patent foramen ovale. Multiple case-control studies have not convincingly shown an association of the inherited thrombophilias with ischemic stroke, even in young patients and patients with patent foramen ovale. If there is an association between the inherited thrombophilias and arterial stroke, then it is a weak one, likely enhanced by other prothrombotic risk factors. The consequences of ordering these tests and attributing causality to an arterial event can result in significant costs to the health care system and pose a potential risk to patients, because this may lead to inappropriate use of long-term oral anticoagulants, exposing patients to harm without a clearly defined benefit.