Testing for Inherited Thrombophilias in Arterial Stroke

Abstract

Background and Purpose-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. Methods-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. Results-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. Conclusion-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. (Stroke. 2010;41:2985-2990.)Key Words: blood coagulation disorders Ⅲ inherited Ⅲ foramen ovale Ⅲ patent Ⅲ stroke Ⅲ thrombophilia P atients with inherited thrombophilias are known to be at increased risk for venous thromboembolism (VTE), but a causal relationship with arterial thrombosis has not been clearly established. The data supporting thrombophilias as a cause of arterial stroke are limited predominantly to case reports and uncontrolled studies with mixed results from meta-analyses. Case-control studies do not consistently support an association of these disorders with stroke. Despite many authorities stating that these tests should not be ordered routinely in the work-up of ischemic stroke, 1-3 many books and articles continue to perpetuate the need to order these tests as part of the stroke work-up, especially in the young. 4,5 We review the current literature on the inherited thrombophilias in ischemic arterial stroke, present a cost and risk-benefit analysis, and suggest when testing should be considered. Materials and MethodsThe PubMed and Ovid Medline databases from 1950 to present were searched using "stroke" combined with the following key words: "thrombophilia," "protein C deficiency," "protein S deficiency," "antithrombin III deficiency," "factor V Leiden," and "prothrombin gene mutation." Additional searches with these terms and "patent foramen ovale" were also performed. Limits of human and English language were imposed, although if abstracts could be obtained in English they were included. All results were searched for relevant data and divided into ca...

Laboratory Investigation of Thrombophilia / LABORATORIJSKO ISPITIVANJE TROMBOFILIJA

“…The association between most well-defined VTE risk factors and arterial thrombosis, such as acute myocardial infarction and ischemic stroke, is not firmly established to date (19)(20)(21). According to the current knowledge, only the presence of antiphospholipid antibodies (aPLAs), hyperhomocysteinemia (HHC) and dysfibrinogenemia can be associated with both venous and arterial thrombosis (22)(23)(24).…”

Ischemic stroke in young adults: an overview of etiological aspects

“…Antiphospholipid antibodies, particularly lupus anticoagulant, are an independent risk factor for IS in young adults 45 . Genetic prothrombotic states play an important role in young patients with cerebral venous thrombosis, but thrombophilia alone rarely causes arterial occlusions 46 . mIgRAINE Considering that migraine affects about 15% of the adult population, migrainous infarct is a rare event in young adults.…”

Prevention of Cardioembolic Stroke

“…A standard prothrombotic laboratory workup for younger patients includes GP20210 (prothrombin gene) mutation, factor V Leiden mutation, protein C or S deficiency, anti-thrombin III deficiency, anti-phospholipid antibodies, and lupus anticoagulant. Recently, hypercoaguable blood testing has come into question, given recent meta-analyses showing a weak association with arterial stroke [12]. However, this may be considered in young patients with no other cause of stroke.…”