PDF herunterladen
Semin Thromb Hemost 2013; 39(08): 913-927
DOI: 10.1055/s-0033-1357504
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Cerebral Venous Thrombosis and Thrombophilia: A Systematic Review and Meta-Analysis

Mandy N. Lauw
1   Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands
2   Department of Hematology, Academic Medical Center, Amsterdam, The Netherlands
*   Mandy N. Lauw and Stefano Barco have contributed equally to this study
,
Stefano Barco
1   Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands
3   Department of Internal Medicine, University of Pavia, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
*   Mandy N. Lauw and Stefano Barco have contributed equally to this study
,
Jonathan M. Coutinho
4   Department of Neurology, Academic Medical Center, Amsterdam, The Netherlands
,
Saskia Middeldorp
1   Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Publikationsdatum:
15. Oktober 2013 (online)

    Lizenzen und Reprints

Abstract

Cerebral venous thrombosis (CVT) is a rare manifestation of venous thromboembolism (VTE) and stroke. The aim of our systematic review was to provide an updated summary of the strength of association between CVT and thrombophilia and to explore the relevance of thrombophilia for recurrence of CVT or other VTE, or other outcome variables. MEDLINE (via PubMed), EMBASE (via Ovid), and CENTRAL were systematically searched, including references of retrieved articles. Cohort studies of ≥ 40 patients and case-control studies comparing the prevalence of thrombophilia in patients with CVT and unrelated controls were eligible. Two reviewers independently selected studies, assessed quality, and extracted data. A meta-analysis was performed for high quality case-control studies with unselected cases and healthy controls. Odds ratios with 95% confidence intervals were calculated and pooled. We included 23 cohort studies and 33 case-control studies. A significant association was demonstrated between CVT and all inherited thrombophilic factors, as well as increased levels of homocysteine. Inconclusive results were found on the relevance of thrombophilia for recurrent CVT or other VTE. Although there is a strong association between CVT and thrombophilia, the clinical relevance of thrombophilia testing in patients with CVT seems limited, similarly to other forms of VTE.

Keywords

cerebral venous thrombosis - meta-analysis - sinus thrombosis - thrombophilia - systematic review
 

  • References

  • 1 Einhäupl K, Stam J, Bousser MG , et al; European Federation of Neurological Societies. EFNS guideline on the treatment of cerebral venous and sinus thrombosis in adult patients. Eur J Neurol 2010; 17 (10) 1229-1235
    CrossrefPubMedSuche in Google Scholar
  • 2 Stam J. Thrombosis of the cerebral veins and sinuses. N Engl J Med 2005; 352 (17) 1791-1798
    CrossrefPubMedSuche in Google Scholar
  • 3 Bousser MG, Ferro JM. Cerebral venous thrombosis: an update. Lancet Neurol 2007; 6 (2) 162-170
    CrossrefPubMedSuche in Google Scholar
  • 4 Coutinho JM, Zuurbier SM, Aramideh M, Stam J. The incidence of cerebral venous thrombosis: a cross-sectional study. Stroke 2012; 43 (12) 3375-3377
    CrossrefPubMedSuche in Google Scholar
  • 5 Coutinho JM, Ferro JM, Canhão P , et al. Cerebral venous and sinus thrombosis in women. Stroke 2009; 40 (7) 2356-2361
    CrossrefPubMedSuche in Google Scholar
  • 6 Cantú C, Barinagarrementeria F. Cerebral venous thrombosis associated with pregnancy and puerperium. Review of 67 cases. Stroke 1993; 24 (12) 1880-1884
    CrossrefPubMedSuche in Google Scholar
  • 7 Heit JA, Silverstein MD, Mohr DN, Petterson TM, O'Fallon WM, Melton III LJ. Risk factors for deep vein thrombosis and pulmonary embolism: a population-based case-control study. Arch Intern Med 2000; 160 (6) 809-815
    CrossrefPubMedSuche in Google Scholar
  • 8 Vossen CY, Conard J, Fontcuberta J , et al. Familial thrombophilia and lifetime risk of venous thrombosis. J Thromb Haemost 2004; 2 (9) 1526-1532
    CrossrefPubMedSuche in Google Scholar
  • 9 Coppens M, Reijnders JH, Middeldorp S, Doggen CJ, Rosendaal FR. Testing for inherited thrombophilia does not reduce the recurrence of venous thrombosis. J Thromb Haemost 2008; 6 (9) 1474-1477
    CrossrefPubMedSuche in Google Scholar
  • 10 Christiansen SC, Cannegieter SC, Koster T, Vandenbroucke JP, Rosendaal FR. Thrombophilia, clinical factors, and recurrent venous thrombotic events. JAMA 2005; 293 (19) 2352-2361
    CrossrefPubMedSuche in Google Scholar
  • 11 Bates SM, Greer IA, Middeldorp S , et al; American College of Chest Physicians. VTE, thrombophilia, antithrombotic therapy, and pregnancy: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2012; 141 (2 Suppl) e691S-e736S
    CrossrefPubMedSuche in Google Scholar
  • 12 Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 2010; 25 (9) 603-605
    CrossrefPubMedSuche in Google Scholar
  • 13 Sanderson S, Tatt ID, Higgins JP. Tools for assessing quality and susceptibility to bias in observational studies in epidemiology: a systematic review and annotated bibliography. Int J Epidemiol 2007; 36 (3) 666-676
    CrossrefPubMedSuche in Google Scholar
  • 14 Wells GA, Shea B, O'Connell D , et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp . Accessed March 3, 2013
    PubMed
  • 15 deVeber G, Andrew M, Adams C , et al; Canadian Pediatric Ischemic Stroke Study Group. Cerebral sinovenous thrombosis in children. N Engl J Med 2001; 345 (6) 417-423
    CrossrefPubMedSuche in Google Scholar
  • 16 Camargo EC, Massaro AR, Bacheschi LA , et al. Ethnic differences in cerebral venous thrombosis. Cerebrovasc Dis 2005; 19 (3) 147-151
    CrossrefPubMedSuche in Google Scholar
  • 17 Terazzi E, Mittino D, Rudà R , et al; Cerebral Venous Thrombosis Group. Cerebral venous thrombosis: a retrospective multicentre study of 48 patients. Neurol Sci 2005; 25 (6) 311-315
    CrossrefPubMedSuche in Google Scholar
  • 18 Wasay M, Bakshi R, Bobustuc G , et al. Cerebral venous thrombosis: analysis of a multicenter cohort from the United States. J Stroke Cerebrovasc Dis 2008; 17 (2) 49-54
    CrossrefPubMedSuche in Google Scholar
  • 19 Coutinho JM, Ferro JM, Canhão P , et al. Cerebral venous and sinus thrombosis in women. Stroke 2009; 40 (7) 2356-2361
    CrossrefPubMedSuche in Google Scholar
  • 20 Algahtani HA, Abdu AP, Shami AM , et al. Cerebral venous sinus thrombosis in Saudi Arabia. Neurosciences (Riyadh) 2011; 16 (4) 329-334
    PubMedSuche in Google Scholar
  • 21 Dentali F, Poli D, Scoditti U , et al; CErebral VEin Thrombosis International Study Investigators. Long-term outcomes of patients with cerebral vein thrombosis: a multicenter study. J Thromb Haemost 2012; 10 (7) 1297-1302
    CrossrefPubMedSuche in Google Scholar
  • 22 Narayan D, Kaul S, Ravishankar K , et al. Risk factors, clinical profile, and long-term outcome of 428 patients of cerebral sinus venous thrombosis: insights from Nizam's Institute Venous Stroke Registry, Hyderabad (India). Neurol India 2012; 60 (2) 154-159
    CrossrefPubMedSuche in Google Scholar
  • 23 Uzar E, Ekici F, Acar A , et al. Cerebral venous sinus thrombosis: an analyses of 47 patients. Eur Rev Med Pharmacol Sci 2012; 16 (11) 1499-1505
    PubMedSuche in Google Scholar
  • 24 Deschiens MA, Conard J, Horellou MH , et al. Coagulation studies, factor V Leiden, and anticardiolipin antibodies in 40 cases of cerebral venous thrombosis. Stroke 1996; 27 (10) 1724-1730
    CrossrefPubMedSuche in Google Scholar
  • 25 de Bruijn SF, de Haan RJ, Stam J ; For The Cerebral Venous Sinus Thrombosis Study Group. Clinical features and prognostic factors of cerebral venous sinus thrombosis in a prospective series of 59 patients. J Neurol Neurosurg Psychiatry 2001; 70 (1) 105-108
    CrossrefPubMedSuche in Google Scholar
  • 26 Breteau G, Mounier-Vehier F, Godefroy O , et al. Cerebral venous thrombosis 3-year clinical outcome in 55 consecutive patients. J Neurol 2003; 250 (1) 29-35
    CrossrefPubMedSuche in Google Scholar
  • 27 Amberger N, Masuhr F, Valdueza JM, Vetter B, Weih M. A negative personal and family history for venous thrombotic events is not sufficient to exclude thrombophilia in patients with cerebral venous thrombosis. Eur J Neurol 2004; 11 (8) 555-558
    CrossrefPubMedSuche in Google Scholar
  • 28 Stolz E, Rahimi A, Gerriets T, Kraus J, Kaps M. Cerebral venous thrombosis: an all or nothing disease? Prognostic factors and long-term outcome. Clin Neurol Neurosurg 2005; 107 (2) 99-107
    CrossrefPubMedSuche in Google Scholar
  • 29 De Stefano V, Fiorini A, Rossi E , et al. Incidence of the JAK2 V617F mutation among patients with splanchnic or cerebral venous thrombosis and without overt chronic myeloproliferative disorders. J Thromb Haemost 2007; 5 (4) 708-714
    CrossrefPubMedSuche in Google Scholar
  • 30 Bellucci S, Cassinat B, Bonnin N, Marzac C, Crassard I. The V617F JAK 2 mutation is not a frequent event in patients with cerebral venous thrombosis without overt chronic myeloproliferative disorder. Thromb Haemost 2008; 99 (6) 1119-1120
    PubMedSuche in Google Scholar
  • 31 Zubkov AY, McBane RD, Brown RD, Rabinstein AA. Brain lesions in cerebral venous sinus thrombosis. Stroke 2009; 40 (4) 1509-1511
    CrossrefPubMedSuche in Google Scholar
  • 32 Alonso-Cánovas A, Masjuan J, González-Valcárcel J , et al. [Cerebral venous thrombosis: when etiology makes the difference]. Neurologia 2009; 24 (7) 439-445
    PubMedSuche in Google Scholar
  • 33 Martinelli I, Bucciarelli P, Passamonti SM, Battaglioli T, Previtali E, Mannucci PM. Long-term evaluation of the risk of recurrence after cerebral sinus-venous thrombosis. Circulation 2010; 121 (25) 2740-2746
    CrossrefPubMedSuche in Google Scholar
  • 34 Aaron S, Alexander M, Maya T , et al. Underlying prothrombotic states in pregnancy associated cerebral venous thrombosis. Neurol India 2010; 58 (4) 555-559
    CrossrefPubMedSuche in Google Scholar
  • 35 Yokus O, Sahin Balcik O, Albayrak M , et al. Evaluation of risk factors for thrombophilia in patients with cerebral venous thrombosis. Turk J Hematol 2010; 27: 162-167
    CrossrefPubMedSuche in Google Scholar
  • 36 Sanz Gallego I, Fuentes B, Martínez-Sánchez P, Díez Tejedor E. Do cerebral venous thrombosis risk factors influence the development of an associated venous infarction?. Neurologia 2011; 26 (1) 13-19
    CrossrefPubMedSuche in Google Scholar
  • 37 Passamonti SM, Biguzzi E, Cazzola M , et al. The JAK2 V617F mutation in patients with cerebral venous thrombosis. J Thromb Haemost 2012; 10 (6) 998-1003
    CrossrefPubMedSuche in Google Scholar
  • 38 Martinelli I, Landi G, Merati G, Cella R, Tosetto A, Mannucci PM. Factor V gene mutation is a risk factor for cerebral venous thrombosis. Thromb Haemost 1996; 75 (3) 393-394
    PubMedSuche in Google Scholar
  • 39 Zuber M, Toulon P, Marnet L, Mas JL. Factor V Leiden mutation in cerebral venous thrombosis. Stroke 1996; 27 (10) 1721-1723
    CrossrefPubMedSuche in Google Scholar
  • 40 Lüdemann P, Nabavi DG, Junker R , et al. Factor V Leiden mutation is a risk factor for cerebral venous thrombosis: a case-control study of 55 patients. Stroke 1998; 29 (12) 2507-2510
    CrossrefPubMedSuche in Google Scholar
  • 41 Hillier CE, Collins PW, Bowen DJ, Bowley S, Wiles CM. Inherited prothrombotic risk factors and cerebral venous thrombosis. QJM 1998; 91 (10) 677-680
    CrossrefPubMedSuche in Google Scholar
  • 42 Weih M, Vetter B, Ziemer S , et al. Increased rate of factor V Leiden mutation in patients with cerebral venous thrombosis. J Neurol 1998; 245 (3) 149-152
    CrossrefPubMedSuche in Google Scholar
  • 43 Christopher R, Nagaraja D, Dixit NS, Narayanan CP. Anticardiolipin antibodies: a study in cerebral venous thrombosis. Acta Neurol Scand 1999; 99 (2) 121-124
    CrossrefPubMedSuche in Google Scholar
  • 44 Madonna P, De Stefano V, Coppola A, Albisinni R, Cerbone AM. G20210A PRTH gene mutation and other trombophilic polymorphisms in patients with cerebral vein thrombosis. Stroke 2000; 31 (7) 1787-1788
    PubMedSuche in Google Scholar
  • 45 Voetsch B, Damasceno BP, Camargo EC , et al. Inherited thrombophilia as a risk factor for the development of ischemic stroke in young adults. Thromb Haemost 2000; 83 (2) 229-233
    PubMedSuche in Google Scholar
  • 46 Bombeli T, Basic A, Fehr J. Prevalence of hereditary thrombophilia in patients with thrombosis in different venous systems. Am J Hematol 2002; 70 (2) 126-132
    CrossrefPubMedSuche in Google Scholar
  • 47 Bonduel M, Sciuccati G, Hepner M , et al. Factor V Leiden and prothrombin gene G20210A mutation in children with cerebral thromboembolism. Am J Hematol 2003; 73 (2) 81-86
    CrossrefPubMedSuche in Google Scholar
  • 48 Heller C, Heinecke A, Junker R , et al; Childhood Stroke Study Group. Cerebral venous thrombosis in children: a multifactorial origin. Circulation 2003; 108 (11) 1362-1367
    CrossrefPubMedSuche in Google Scholar
  • 49 Martinelli I, Battaglioli T, Pedotti P, Cattaneo M, Mannucci PM. Hyperhomocysteinemia in cerebral vein thrombosis. Blood 2003; 102 (4) 1363-1366
    CrossrefPubMedSuche in Google Scholar
  • 50 Boncoraglio G, Carriero MR, Chiapparini L , et al. Hyperhomocysteinemia and other thrombophilic risk factors in 26 patients with cerebral venous thrombosis. Eur J Neurol 2004; 11 (6) 405-409
    CrossrefPubMedSuche in Google Scholar
  • 51 Cantu C, Alonso E, Jara A , et al. Hyperhomocysteinemia, low folate and vitamin B12 concentrations, and methylene tetrahydrofolate reductase mutation in cerebral venous thrombosis. Stroke 2004; 35 (8) 1790-1794
    CrossrefPubMedSuche in Google Scholar
  • 52 Ventura P, Cobelli M, Marietta M, Panini R, Rosa MC, Salvioli G. Hyperhomocysteinemia and other newly recognized inherited coagulation disorders (factor V Leiden and prothrombin gene mutation) in patients with idiopathic cerebral vein thrombosis. Cerebrovasc Dis 2004; 17 (2-3) 153-159
    PubMedSuche in Google Scholar
  • 53 Tufano A, Coppola A, Varricchione N , et al. Predisposing factors in patients with early-onset cerebral vein thrombosis. Thromb Res 2005; 115 (5) 439-440
    CrossrefPubMedSuche in Google Scholar
  • 54 Kenet G, Waldman D, Lubetsky A , et al. Paediatric cerebral sinus vein thrombosis. A multi-center, case-controlled study. Thromb Haemost 2004; 92 (4) 713-718
    PubMedSuche in Google Scholar
  • 55 Rodrigues CA, Rocha LK, Morelli VM, Franco RF, Lourenço DM. Prothrombin G20210A mutation, and not factor V Leiden mutation, is a risk factor for cerebral venous thrombosis in Brazilian patients. J Thromb Haemost 2004; 2 (7) 1211-1212
    CrossrefPubMedSuche in Google Scholar
  • 56 Le Cam-Duchez V, Bagan-Triquenot A, Ménard JF, Mihout B, Borg JY. Association of the protein C promoter CG haplotype and the factor II G20210A mutation is a risk factor for cerebral venous thrombosis. Blood Coagul Fibrinolysis 2005; 16 (7) 495-500
    CrossrefPubMedSuche in Google Scholar
  • 57 Gadelha T, André C, Jucá AA, Nucci M. Prothrombin 20210A and oral contraceptive use as risk factors for cerebral venous thrombosis. Cerebrovasc Dis 2005; 19 (1) 49-52
    CrossrefPubMedSuche in Google Scholar
  • 58 Dindagur N, Kruthika-Vinod TP, Christopher R. Thrombophilic gene polymorphisms in puerperal cerebral veno-sinus thrombosis. J Neurol Sci 2006; 249 (1) 25-30
    CrossrefPubMedSuche in Google Scholar
  • 59 Lichy C, Dong-Si T, Reuner K , et al. Risk of cerebral venous thrombosis and novel gene polymorphisms of the coagulation and fibrinolytic systems. J Neurol 2006; 253 (3) 316-320
    CrossrefPubMedSuche in Google Scholar
  • 60 Bugnicourt JM, Roussel B, Tramier B, Lamy C, Godefroy O. Cerebral venous thrombosis and plasma concentrations of factor VIII and von Willebrand factor: a case control study. J Neurol Neurosurg Psychiatry 2007; 78 (7) 699-701
    PubMedSuche in Google Scholar
  • 61 Colaizzo D, Amitrano L, Iannaccone L , et al. Gain-of-function gene mutations and venous thromboembolism: distinct roles in different clinical settings. J Med Genet 2007; 44 (6) 412-416
    CrossrefPubMedSuche in Google Scholar
  • 62 Stolz E, Valdueza JM, Grebe M , et al. Anemia as a risk factor for cerebral venous thrombosis? An old hypothesis revisited. Results of a prospective study. J Neurol 2007; 254 (6) 729-734
    CrossrefPubMedSuche in Google Scholar
  • 63 Cesarman-Maus G, Cantú-Brito C, Barinagarrementeria F , et al. Autoantibodies against the fibrinolytic receptor, annexin A2, in cerebral venous thrombosis. Stroke 2011; 42 (2) 501-503
    CrossrefPubMedSuche in Google Scholar
  • 64 Laugesaar R, Kahre T, Kolk A, Uustalu U, Kool P, Talvik T. Factor V Leiden and prothrombin 20210G>A [corrected] mutation and paediatric ischaemic stroke: a case-control study and two meta-analyses. Acta Paediatr 2010; 99 (8) 1168-1174
    CrossrefPubMedSuche in Google Scholar
  • 65 Rahimi Z, Mozafari H, Bigvand AH , et al. Cerebral venous and sinus thrombosis and thrombophilic mutations in Western Iran: association with factor V Leiden. Clin Appl Thromb Hemost 2010; 16 (4) 430-434
    CrossrefPubMedSuche in Google Scholar
  • 66 Ringelstein M, Jung A, Berger K , et al. Promotor polymorphisms of plasminogen activator inhibitor-1 and other thrombophilic genotypes in cerebral venous thrombosis: a case-control study in adults. J Neurol 2012; 259 (11) 2287-2292
    CrossrefPubMedSuche in Google Scholar
  • 67 Ashjazadeh N, Poursadeghfard M, Farjadian S. Factor V G1691A and prothrombin G20210A gene polymorphisms among Iranian patients with cerebral venous thrombosis. . Neurol Asia 2012; 17 (3) 199-203
    PubMedSuche in Google Scholar
  • 68 Ben Salem-Berrabah O, Fekih-Mrissa N, N'siri B , et al. Thrombophilic polymorphisms - factor V Leiden G1691A, prothrombin G20210A and MTHFR C677T - in Tunisian patients with cerebral venous thrombosis. J Clin Neurosci 2012; 19 (9) 1326-1327
    CrossrefPubMedSuche in Google Scholar
  • 69 Libourel EJ, ten Kate MK, Brouwer JL, Veeger NJ, van der Meer J. Contribution of multiple thrombophilic and transient risk factors in the development of cerebral venous thrombosis. Thromb Res 2007; 121 (3) 301-307
    CrossrefPubMedSuche in Google Scholar
  • 70 Wysokinska EM, Wysokinski WE, Brown RD , et al. Thrombophilia differences in cerebral venous sinus and lower extremity deep venous thrombosis. Neurology 2008; 70 (8) 627-633
    CrossrefPubMedSuche in Google Scholar
  • 71 Martinelli I, Sacchi E, Landi G, Taioli E, Duca F, Mannucci PM. High risk of cerebral-vein thrombosis in carriers of a prothrombin-gene mutation and in users of oral contraceptives. N Engl J Med 1998; 338 (25) 1793-1797
    CrossrefPubMedSuche in Google Scholar
  • 72 Girot M, Ferro JM, Canhão P , et al; ISCVT Investigators. Predictors of outcome in patients with cerebral venous thrombosis and intracerebral hemorrhage. Stroke 2007; 38 (2) 337-342
    CrossrefPubMedSuche in Google Scholar
  • 73 Gosk-Bierska I, Wysokinski W, Brown Jr RD , et al. Cerebral venous sinus thrombosis: Incidence of venous thrombosis recurrence and survival. Neurology 2006; 67 (5) 814-819
    CrossrefPubMedSuche in Google Scholar
  • 74 Dentali F, Crowther M, Ageno W. Thrombophilic abnormalities, oral contraceptives, and risk of cerebral vein thrombosis: a meta-analysis. Blood 2006; 107 (7) 2766-2773
    CrossrefPubMedSuche in Google Scholar
  • 75 Kenet G, Lütkhoff LK, Albisetti M , et al. Impact of thrombophilia on risk of arterial ischemic stroke or cerebral sinovenous thrombosis in neonates and children: a systematic review and meta-analysis of observational studies. Circulation 2010; 121 (16) 1838-1847
    CrossrefPubMedSuche in Google Scholar
  • 76 Dayan N, Holcroft CA, Tagalakis V. The risk of venous thrombosis, including cerebral vein thrombosis, among women with thrombophilia and oral contraceptive use: a meta-analysis. Clin Appl Thromb Hemost 2011; 17 (6) E141-E152
    CrossrefPubMedSuche in Google Scholar
  • 77 Marjot T, Yadav S, Hasan N, Bentley P, Sharma P. Genes associated with adult cerebral venous thrombosis. Stroke 2011; 42 (4) 913-918
    CrossrefPubMedSuche in Google Scholar
  • 78 Bloemenkamp KW, Rosendaal FR, Helmerhorst FM, Vandenbroucke JP. Higher risk of venous thrombosis during early use of oral contraceptives in women with inherited clotting defects. Arch Intern Med 2000; 160 (1) 49-52
    CrossrefPubMedSuche in Google Scholar
  • 79 de Bruijn SF, Stam J, Koopman MM, Vandenbroucke JP ; The Cerebral Venous Sinus Thrombosis Study Group Case-control study of risk of cerebral sinus thrombosis in oral contraceptive users and in [correction of who are] carriers of hereditary prothrombotic conditions. BMJ 1998; 316 (7131) 589-592
    CrossrefPubMedSuche in Google Scholar
  • 80 Cohn DM, Vansenne F, de Borgie CA, Middeldorp S. Thrombophilia testing for prevention of recurrent venous thromboembolism. Cochrane Database Syst Rev 2012; 12: CD007069
    PubMedSuche in Google Scholar
  • 81 Junker R, Nabavi DG, Wolff E , et al. Plasminogen activator inhibitor-1 4G/4G-genotype is associated with cerebral sinus thrombosis in factor V Leiden carriers. Thromb Haemost 1998; 80 (4) 706-707
    PubMedSuche in Google Scholar