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Thromb Haemost 2009; 101(01): 145-150
DOI: 10.1160/TH07-12-0754
DOI: 10.1160/TH07-12-0754
Cardiovascular Biology and Cell Signalling
Ischaemic stroke patients with heterozygous factor V Leiden present with multiple brain infarctions and widespread atherothrombotic disease
Financial support: This study was supported by the Finnish Medical Foundation, the Finnish Cultural Foundation, the Paulo Foundation, the Aarne Koskelo Foundation, the Biomedicum Foundation, and the Helsinki University Central Hospital.
Further Information
Publication History
Received:
27 December 2007
Accepted after major revision:
17 October 2008
Publication Date:
23 November 2017 (online)
Summary
Factor V Leiden (FVL) mutation is a risk factor for venous and, to a degree, arterial thrombosis. It is unknown whether and how FVL affects the manifestations of ischaemic stroke (IS). We assessed the clinical, laboratory, radiological, and prognostic characteristics in an observational study with adult IS patients having FVL. We tested 860 patients with first-ever IS for FVL and found 48 FVL positive patients. Detailed clinical, laboratory, and radiological evaluation were compared with that of 144 (1:3) gender and age matched IS patients without FVL. All patients underwent a prognostic evaluation at an average of five years follow-up. Despite the relatively young age (mean 48.5 years, range 44–54 years) of the FVL positive IS patients, peripheral arterial occlusive disease (PAOD), coronary artery disease (CAD), and previous transient cerebrovascular event occurred more frequently compared with controls. Family history of cardiovascular disease (CVD) and multiple silent brain infarctions were revealed in half of the FVL positive patients, whereas these were seldom encountered among controls. Stroke severity, long-term recovery, and recurrence rates seemed similar irrespective of FVL status. Our findings indicate that the clinical profile of IS patients with FVL associated with wider manifestation of atherothrombosis, positive family history of arterial thrombosis, and presence of multiple silent infarctions on brain images.
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References
- 1 Bertina R, Koeleman B, Koster T. et al. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 1994; 369: 64-67.
- 2 Dahlbäck B. Activated protein C resistance and thrombosis: molecular mechanism of hypercoagulable state due to FVR506Q mutation. Semin Thromb Hemost 1999; 25: 273-289.
- 3 Kim R, Becker R. Association between factor V Leiden, prothrombin G20210A, and methylenetetrahydrofolate reductase C677T mutations and events of the arterial circulatory system: a meta-analysis of published studies. Am Heart J 2003; 146: 948-957.
- 4 Marcucci R, Sofi R, Fedi S. et al. Thrombophilic risk factors in patients with severe carotid atherosclerosis. J Thromb Haemost 2005; 03: 502-507.
- 5 Juul K, Tybjærg-Hansen A, Steffensen R. et al. Factor V Leiden: the Copenhagen City Heart Study and 2 meta-analyses. Blood 2002; 100: 3-10.
- 6 Casas J, Hingorani A, Bautista L. et al. Mate-analysis of genetic studies in ischemic stroke: thirty-two genes involvimg approximately 18,000 cases and 58,000 controls. Arch Neurol 2004; 61: 1652-1661.
- 7 Kenet G, Sadetzki S, Murad H. et al. Factor V Leiden and antiphospholipid antibodies are significant risk factors for ischemic stroke in children. Stroke 2000; 31: 283-1288.
- 8 Martinelli I, Battaglioli T, Burgo I. et al. Oral contraceptive use, thrombophilia and their interaction in young women with ischemic stroke. Haematologica 2006; 91: 844-847.
- 9 Rosendaal F, Siscovick D, Schwartz S. et al. Factor V Leiden (resistance to activated protein C) increases the risk of myocardial infarction in young women. Blood 1997; 89: 2817-2821.
- 10 Slooter A, Rosendaal F, Tanis B. et al. Prothrombotic conditions, oral contraceptives, and risk of ischemic stroke. J Thromb Haemost 2005; 03: 1213-1217.
- 11 Kontula K, Ylikorkala A, Miettinen H. et al. Arg506Gln factor V mutation (factor V Leiden) in patients with ischaemic cerebrovascular disease and survivors of myocardial infarction. Thromb Haemost 1995; 73: 558-560.
- 12 Lalouschek W, Suess E, Aull S. et al. Clinical and laboratory data in heterozygous factor V Leiden mutation positive versus negative patients with TIA and minor stroke. Stroke 1995; 26: 1963-1964.
- 13 Zunker P, Hohenstein C, Plendl H-J. et al. Activated protein C resistance and acute ischemic stroke: relation to stroke causation and age. J Neurol 2001; 248: 701-704.
- 14 Hankey G, Eikelboom J, van Bockxmeer F. et al. Inherited thrombophilia in ischemic stroke and its pathogenic subtypes. Stroke 2001; 32: 1793-1799.
- 15 Goldstein L, Adams R, Alberts M. et al. Primary prevention of ischemic stroke. Stroke 2006; 37: 1583-1633.
- 16 European stroke initiative recommendations for stroke management-update 2003. Cerebrovasc Dis 2003; 16: 311-337.
- 17 Bamford J, Sandercock P, Dennis M. et al. Classification and natural history of clinically identifiable subtypes of cerebral infarction. Lancet 1991; 337: 1521-1526.
- 18 Blennow K, Wallin A, Uhlemann C. et al. Whitematter lesions on CT in Alzheimer patients: relation to clinical symptomatology and vascular factors. Acta Neurol Scand 1991; 83: 187-193.
- 19 Szolnoki Z, Samogyvári F, Kondacs A. et al. Evalution of the interactions of common genetic mutations in stroke patients. J Neurol 2002; 249: 1391-1397.
- 20 Haapaniemi E, Tatlisumak T, Soinne L. et al. Natural anticoagulants (antithrombin III, protein C, and protein S) in patients with mild to moderate ischemic stroke. Acta Neurol Scand 2002; 105: 107-114.
- 21 Haapaniemi E, Helenius J, Soinne L. et al. Serial measurements of plasma homocysteine levels in early and late phases of ischemic stroke. Eur J Neurol 2007; 14: 12-17.
- 22 Gruber A, Griffin J. Direct detection of activated protein C in blood from human subjects. Blood 1992; 79: 2340-2348.
- 23 Sampram E, Lindblad B, Dahlback B. Activated protein C resistance in patients with peripheral vascular disease. J Vasc Surg 1998; 28: 624-629.
- 24 Reny J, Alhenc-Gelas M, Fontana P. et al. The factor II G20210A gene polymorphism, but not factor V Arg506Gln, is associated with peripheral arterial disease results of a case-control study. J Thromb Haemost 2004; 02: 1334-1340.
- 25 Mueller T, Marschon R, Dieplinger B. et al. Factor V Leiden, prothrombin G20210A, and methylenetetrahydrofolate reductase C677T mutations are not associated with chronic limb ischemia: the Linz Peripheral Arterial Disease (LIPAD) study. J Vasc Surg 2005; 41: 808-815.
- 26 Sofi F, Lari B, Rogolino A. et al. Thrombophilic risk factors for symptomatic peripheral arterial disease. J Vasc Surg 2005; 41: 255-260.
- 27 Gardemann A, Arsic T, Katz N. et al. The factor II G20210A and factor V G1691A gene transitions and coronory heart disease. Thromb Haemost 1999; 81: 208-213.
- 28 Mansourati J, Da Costa A, Munier S. et al. Prevalence of factor V Leiden in patients with myocardial infarction and normal coronary angiography. Thromb Haemost 2000; 83: 822-825.
- 29 Voetsch B, Damasceno B, Camargo E. et al. Inherited thrombophilia as a risk factor for the development of ischemic stroke in young adult. Thromb Haemost 2000; 83: 229-233.
- 30 Ye Z, Liu E, Higgins J. et al. Seven haemostatic gene polymorphisms in coronory disease: meta-analysis of 66,155 cases and 91,307 controls. Lancet 2006; 367: 651-658.
- 31 Eskandari M, Bontempo F, Hassett A. et al. Arterial thromboembolic events in patients with the factor V Leiden mutation. Am J Surg 1998; 176: 122-125.
- 32 Rallidis L, Belesi C, Manioudaki H. et al. Myocadrial infarction under the age of 36: prevalence of thrombophilic disorders. Thromb Haemost 2003; 90: 272-279.
- 33 Glueck C, Wang P, Fontaine R. et al. Estrogen replacement therapy, thrombophilia, and atherothrombosis. Metabolism 2002; 51: 724-732.
- 34 Hobikoglu G, Akyuz U, Akyuz F. et al. Factor V Leiden is a risk factor for myocardial infarction in young Turkish men. Acta Cardiol 2004; 59: 594-597.
- 35 Sabino A, Ribeiro D, Carvalho M. et al. Factor V Leiden and increased risk for arterial thrombotic disease in young Brazilian patients. Blood Coagul Fibrinolysis 2006; 17: 271-275.
- 36 Willeit J, Kiechl S, Oberhollenzer F. et al. Distinct risk profiles of early and advanced atherosclerosis: prospective results from the Bruneck Study. Arterioscler Thromb Vasc Biol 2000; 20: 529-537.
- 37 Provenzale J, Barboriak D, Davey I. et al. Cerebrovascular disease risk factors: neuroradiologic findings in patients with activated protein C resistance. Radiology 1998; 207: 85-89.
- 38 Szolnoki Z, Somogyvari F, Kondacs A. et al. Evaluation of the roles of the Leiden V mutation and ACE I/D polymorphism in subtypes of ischemic stroke. J Neurol 2001; 248: 756-761.
- 39 Adachi T, Kobayashi S, Yamaguchi S. Frequency and pathogenesis of silent subcortical brain infarction in acute first-ever ischemic stroke. Intern Med 2002; 41: 103-108.
- 40 Pohjasvaara T, Mäntylä R, Aronen H. et al. Clinical and radiological determinations of prestroke cognitive decline in a stroke cohort. J Neurol Neurosurg Psychiatry 1999; 67: 742-748.
- 41 Mok V, Wong A, Lam W. et al. Cognitive impairment and functional outcome after stroke associated with small vessel disease. J Neurol Neurosurg Psychiatry 2004; 75: 560-566.
- 42 Vermeer S, Longstreth Jr W, Koudstaal P. Silent brain infarcts: a systematic review. Lancet Neurol 2007; 06: 611-619.
- 43 Knuiman M, Folsom A, Chambless L. et al. Association of hemostatic variables with MRI-detected cerebral abnormalities: the atherosclerosis risk in communities study. Neuroepidemiology 2001; 20: 96-104.
- 44 Pruissen D, Kappelle L, Algra A. Polymorphisms and risk of ischemic stroke (POLARIS) study: rationale and design. Eur Neurol 2004; 51: 30-34.