Journal of Thrombosis and Thrombolysis

, Volume 20, Issue 2, pp 127–132

Antithrombotic Therapy for Stroke in Young Adults



Stroke in young adults is a markedly heterogeneous disease, and remains an understudied phenomenon. While advances are being made in our understanding of the pathophysiology of its underlying conditions, treatment concerns are controversial, and clinical trials are sorely lacking. This review presents an overview of some of the relevant management issues in hypercoagulable states, migraine, patent foramen ovale, vascular dissection and venous sinus thrombosis.

Key Words

hypercoagulable migraine “patent foramen ovale” “venous sinus thrombosis” thromboembolism dissection 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Adams HP, Jr., Butler MJ, Biller J, Toffol GJ. Nonhemorrhagic cerebral infarction in young adults. Arch Neurol 1986;43:793–796.PubMedGoogle Scholar
  2. 2.
    Sacco RL, Ellenberg JH, Mohr JP, et al. Infarcts of undetermined cause: The NINCDS stroke data bank. Ann Neurol 1989;25:382–390.CrossRefPubMedGoogle Scholar
  3. 3.
    You RX, McNeil JJ, O'Malley HM, Davis SM, Thrift AG, Donnan GA. Risk factors for stroke due to cerebral infarction in young adults. Stroke 1997;28:1913–1918.PubMedGoogle Scholar
  4. 4.
    Adams HP, Jr., Kappelle LJ, Biller J, Gordon DL, Love BB, Gomez F, Heffner M. Ischemic stroke in young adults. Experience in 329 patients enrolled in the Iowa registry of stroke in young adults. Arch Neurol 1995;52:491–495.PubMedGoogle Scholar
  5. 5.
    Kasner S. Stroke treatment—specific considerations. Neurologic Clinics 2000;18:399–417.CrossRefPubMedGoogle Scholar
  6. 6.
    Egeberg O. Inherited antithrombin deficiency causing thrombophilia. Thromb Diath Haemorrh 1965;13:516–530.PubMedGoogle Scholar
  7. 7.
    Thomas R. Hypercoagulability syndromes. Archives of Internal Medicine 2001;161:2433–2439.CrossRefPubMedGoogle Scholar
  8. 8.
    Nicolaes G, Dahlback, B. Activated protein c resistance (FV leiden) and thrombosis: Factor V mutations causing hypercoagulable states. Hemotology/Oncology Clinics of North America 2003;17:37–61.CrossRefGoogle Scholar
  9. 9.
    Kearon C, Crowther, M, Hirsh, J. Managment of patients with hereditary hypercoagulable disorders. Annual Review of Medicine 2000;51:169–185.CrossRefPubMedGoogle Scholar
  10. 10.
    Simioni P, de Ronde H, Prandoni P, Saladini M, Bertina RM, Girolami A. Ischemic stroke in young patients with activated protein C resistance. A report of three cases belonging to three different kindreds. Stroke 1995;26:885–890.PubMedGoogle Scholar
  11. 11.
    Markus HS, Hambley H. Neurology and the blood: Haematological abnormalities in ischaemic stroke. J Neurol Neurosurg Psychiatry 1998;64:150–159.PubMedGoogle Scholar
  12. 12.
    Hassan A, Markus HS. Genetics and ischaemic stroke. Brain 2000;123(Pt 9):1784–1812.CrossRefPubMedGoogle Scholar
  13. 13.
    Chaturvedi S, Dzieczkowski, J. Multiple hemostatic abnormalities in young adults with activated protein C resistance and cerebral ischemia. Journal of the Neurological Sciences 1998;159:209–212.CrossRefPubMedGoogle Scholar
  14. 14.
    van der Bom JG, Bots ML, Haverkate F, et al. Reduced response to activated protein C is associated with increased risk for cerebrovascular disease. Ann Intern Med 1996;125:265–269.PubMedGoogle Scholar
  15. 15.
    Longstreth WT, Jr., Rosendaal FR, Siscovick DS, Vos HL, Schwartz SM, Psaty BM, Raghunathan TE, Koepsell TD, Reitsma PH. Risk of stroke in young women and two prothrombotic mutations: Factor V Leiden and prothrombin gene variant (g20210a). Stroke 1998;29:577–580.PubMedGoogle Scholar
  16. 16.
    Buller HR, Agnelli G, Hull RD, Hyers TM, Prins MH, Raskob GE. Antithrombotic therapy for venous thromboembolic disease: The seventh ACCP conference on antithrombotic and thrombolytic therapy. Chest 2004;126:401S–428S.CrossRefPubMedGoogle Scholar
  17. 17.
    Geerts WH, Pineo GF, Heit JA, et al. Prevention of venous thromboembolism: The seventh ACCP conference on antithrombotic and thrombolytic therapy. Chest 2004;126:338S–400S.CrossRefPubMedGoogle Scholar
  18. 18.
    Kearon C, Gent M, Hirsh J, et al. A comparison of three months of anticoagulation with extended anticoagulation for a first episode of idiopathic venous thromboembolism. N Engl J Med 1999;340:901–907.CrossRefPubMedGoogle Scholar
  19. 19.
    Schulman S, Granqvist S, Holmstrom M, et al. The duration of oral anticoagulant therapy after a second episode of venous thromboembolism. The duration of anticoagulation trial study group. N Engl J Med 1997;336:393–398.CrossRefPubMedGoogle Scholar
  20. 20.
    Bauer K. Management of thrombophilia. Journal of Thrombosis and Haemostasis 2003;1:1429–1434.CrossRefPubMedGoogle Scholar
  21. 21.
    Prandoni P, Lensing AW, Cogo A, et al. The long-term clinical course of acute deep venous thrombosis. Ann Intern Med 1996;125:1–7.PubMedGoogle Scholar
  22. 22.
    van den Belt AG, Sanson BJ, Simioni P, et al. Recurrence of venous thromboembolism in patients with familial thrombophilia. Arch Intern Med 1997;157:2227–2232.CrossRefPubMedGoogle Scholar
  23. 23.
    Finazzi G, Brancaccio V, Moia M, et al. Natural history and risk factors for thrombosis in 360 patients with antiphospholipid antibodies: A four-year prospective study from the italian registry. Am J Med 1996;100:530–536.CrossRefPubMedGoogle Scholar
  24. 24.
    Bick RL. Antiphospholipid thrombosis syndromes: Etiology, pathophysiology, diagnosis and management. Int J Hematol 1997;65:193–213.CrossRefPubMedGoogle Scholar
  25. 25.
    Moll S, Ortel TL. Monitoring warfarin therapy in patients with lupus anticoagulants. Ann Intern Med 1997;127:177–185.PubMedGoogle Scholar
  26. 26.
    Khamashta M, Cuadrado MJ, Mujic F, Taub NA, Hunt BJ, Hughes GRV. The management of thrombosis in the antiphospholipid-antibody syndrome. New England Journal of Medicine 1995;332:993–997.CrossRefPubMedGoogle Scholar
  27. 27.
    Bick RL, Kaplan H. Syndromes of thrombosis and hypercoagulability. Congenital and acquired causes of thrombosis. Med Clin North Am 1998;82:409–458.CrossRefPubMedGoogle Scholar
  28. 28.
    Sanna G, Bertolaccini ML, Mathieu A. Central nervous system lupus: A clinical approach to therapy. Lupus 2003;12:935–942.CrossRefPubMedGoogle Scholar
  29. 29.
    Kruit M, van Buchem MA, Hofman PAM, et al. Migraine as a risk factor for subclinical brain lesions. Journal of the American Medical Association 2004;291:427–434.CrossRefPubMedGoogle Scholar
  30. 30.
    Schwaag S, Nabavi DG, Frese A, Husstedt IW, Evers S. The association between migraine and juvenile stroke: A case-control study. Headache 2003;43:90–95.CrossRefPubMedGoogle Scholar
  31. 31.
    Mosek A, Marom R, Korczyn AD, Bornstein N. A history of migraine is not a risk factor to develop an ischemic stroke in the elderly. Headache 2001;41:399–401.CrossRefPubMedGoogle Scholar
  32. 32.
    Hering-Hanit R, Friedman Z, Schlesinger I, Ellis M. Evidence for activation of the coagulation system in migraine with aura. Cephalalgia 2001;21:137–139.CrossRefPubMedGoogle Scholar
  33. 33.
    Tzourio C, Tehindrazanarivelo A, Iglesias S, et al. Case-control study of migraine and risk of ischaemic stroke in young women. British Medical Journal 1995;310:830–833.PubMedGoogle Scholar
  34. 34.
    Etminan M, Takkouche B, Caamaño I, Samii A. Risk of ischaemic stroke in people with migraine: Systematic review and meta-analysis of observational studies. British Medical Journal.doi:10.1136/bmj.38302.504063.504068F (published 504013 December 502004).Google Scholar
  35. 35.
    Salobir B, Sabovic M, Peternel P, Stegnar M, Grad A. Classic risk factors, hypercoagulability and migraine in young women with cerebral lacunar infarctions. Acta Neurol Scand 2002;105:189–195.CrossRefPubMedGoogle Scholar
  36. 36.
    Crassard I, Conard J, Bousser MG. Migraine and haemostasis. Cephalalgia 2001;21:630–636.CrossRefPubMedGoogle Scholar
  37. 37.
    Iniesta JA, Corral J, Gonzalez-Conejero R, Rivera J, Vicente V. Prothrombotic genetic risk factors in patients with coexisting migraine and ischemic cerebrovascular disease. Headache 1999;39:486–489.CrossRefPubMedGoogle Scholar
  38. 38.
    Klopstock T, May A, Seibel P, Papagiannuli E, Diener HC, Reichmann H. Mitochondrial DNA in migraine with aura. Neurology 1996;46:1735–1738.PubMedGoogle Scholar
  39. 39.
    Wammes-van der Heijden EA, Tijssen CC, van't Hoff AR, Egberts AC. A thromboembolic predisposition and the effect of anticoagulants on migraine. Headache 2004;44:399–402.CrossRefPubMedGoogle Scholar
  40. 40.
    Tietjen GE. Stroke and migraine linked by silent lesions. Lancet Neurol 2004;3:267.CrossRefPubMedGoogle Scholar
  41. 41.
    Masuhr F, Mehraein S, Einhaupl K. Cerebral venous and sinus thrombosis. J Neurol 2004;251:11–23.CrossRefPubMedGoogle Scholar
  42. 42.
    Stolz E, Kemkes-Matthes B, Potzsch B, et al. Screening for thrombophilic risk factors among 25 German patients with cerebral venous thrombosis. Acta Neurol Scand 2000;102:31–36.CrossRefPubMedGoogle Scholar
  43. 43.
    Brey RL, Coull BM. Cerebral venous thrombosis. Role of activated protein C resistance and factor V gene mutation. Stroke 1996;27:1719–1720.PubMedGoogle Scholar
  44. 44.
    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;27:1724–1730.PubMedGoogle Scholar
  45. 45.
    Dulli DA, Luzzio CC, Williams EC, Schutta HS. Cerebral venous thrombosis and activated protein c resistance. Stroke 1996;27:1731–1733.PubMedGoogle Scholar
  46. 46.
    Zuber M, Toulon P, Marnet L, Mas JL. Factor V Leiden mutation in cerebral venous thrombosis. Stroke 1996;27:1721–1723.PubMedGoogle Scholar
  47. 47.
    Reuner KH, Ruf A, Grau A, et al. Prothrombin gene g20210—<a transition is a risk factor for cerebral venous thrombosis. Stroke 1998;29:1765–1769.PubMedGoogle Scholar
  48. 48.
    Allroggen H, Abbott, RJ. Cerebral venous sinus thrombosis. Postgraduate Medical Journal 2000;76:12–15.CrossRefPubMedGoogle Scholar
  49. 49.
    Einhaupl KM, Villringer A, Meister W, et al. Heparin treatment in sinus venous thrombosis. Lancet 1991;338:597–600.CrossRefPubMedGoogle Scholar
  50. 50.
    Frey JL, Muro GJ, McDougall CG, Dean BL, Jahnke HK. Cerebral venous thrombosis: Combined intrathrombus RTPA and intravenous heparin. Stroke 1999;30:489–494.PubMedGoogle Scholar
  51. 51.
    de Bruijn SF, Stam J. Randomized, placebo-controlled trial of anticoagulant treatment with low-molecular-weight heparin for cerebral sinus thrombosis. Stroke 1999;30:484–488.PubMedGoogle Scholar
  52. 52.
    Stam J, de Bruijn, S, deVeber, G. Anticoagulation for cerebral sinus thrombosis. Stroke 2002;34:1054–1055.CrossRefGoogle Scholar
  53. 53.
    Bousser MG. Cerebral venous thrombosis: Nothing, heparin, or local thrombolysis? Stroke 1999;30:481–483.PubMedGoogle Scholar
  54. 54.
    Bousser MG. Cerebral venous thrombosis: Diagnosis and management. J Neurol 2000;247:252–258.CrossRefPubMedGoogle Scholar
  55. 55.
    Uthman I, Khalil I, Sawaya R, Taher A. Lupus anticoagulant, factor V Leiden, and methylenetetrahydrofolate reductase gene mutation in a lupus patient with cerebral venous thrombosis. Clin Rheumatol 2004;23:362–363.PubMedGoogle Scholar
  56. 56.
    Seligsohn U, Lubetsky A. Genetic susceptibility to venous thrombosis. N Engl J Med 2001;344:1222–1231.CrossRefPubMedGoogle Scholar
  57. 57.
    Seligsohn U, Lubetsky A. Thrombophilia [letter]. N Engl J Med 2001;345:698–699.Google Scholar
  58. 58.
    Leys D, Lucas C, Gobert M, Deklunder G, Pruvo JP. Cervical artery dissections. Eur Neurol 1997;37:3–12.PubMedGoogle Scholar
  59. 59.
    Lyrer P, Engelter S. Antithrombotic drugs for carotid artery dissection. Cochrane Database Syst Rev 2003:CD000255.Google Scholar
  60. 60.
    Schievink WI. Spontaneous dissection of the carotid and vertebral arteries. N Engl J Med 2001;344:898–906.CrossRefPubMedGoogle Scholar
  61. 61.
    Srinivasan J, Newell DW, Sturzenegger M, Mayberg MR, Winn HR. Transcranial doppler in the evaluation of internal carotid artery dissection. Stroke 1996;27:1226–1230.PubMedGoogle Scholar
  62. 62.
    Lucas C, Moulin T, Deplanque D, Tatu L, Chavot D. Stroke patterns of internal carotid artery dissection in 40 patients. Stroke 1998;29:2646–2648.PubMedGoogle Scholar
  63. 63.
    Beletsky V, Nadareishvili Z, Lynch J, Shuaib A, Woolfenden A, Norris JW. Cervical arterial dissection: Time for a therapeutic trial? Stroke 2003;34:2856–2860.CrossRefPubMedGoogle Scholar
  64. 64.
    Schievink W. The treatment of spontaneous carotid and vertebral artery dissections. Current Opinion in Cardiology 2000;15:316–321.CrossRefPubMedGoogle Scholar
  65. 65.
    Windecker S, Meier B. Patent foramen ovale and atrial septal aneurysm: When and how should they be treated. ACC Current Journal Review 2002;11:97–101.CrossRefGoogle Scholar
  66. 66.
    Meier B, Lock, JE. Contemporary management of patent formamen ovale. Circulation 2003;107:5–9.CrossRefPubMedGoogle Scholar
  67. 67.
    Lechat P, Mas JL, Lascault G, et al. Prevalence of patent foramen ovale in patients with stroke. N Engl J Med 1988;318:1148–1152.PubMedGoogle Scholar
  68. 68.
    Webster MW, Chancellor AM, Smith HJ, et al. Patent foramen ovale in young stroke patients. Lancet 1988;332:11–12.CrossRefGoogle Scholar
  69. 69.
    Di Tullio M, Sacco RL, Gopal A, Mohr JP, Homma S. Patent foramen ovale as a risk factor for cryptogenic stroke. Ann Intern Med 1992;117:461–465.PubMedGoogle Scholar
  70. 70.
    Mas JL, Zuber M. Recurrent cerebrovascular events in patients with patent foramen ovale, atrial septal aneurysm, or both and cryptogenic stroke or transient ischemic attack. French study group on patent foramen ovale and atrial septal aneurysm. Am Heart J 1995;130:1083–1088.CrossRefPubMedGoogle Scholar
  71. 71.
    Bogousslavsky J, Garazi S, Jeanrenaud X, Aebischer N, Van Melle G. Stroke recurrence in patients with patent foramen ovale: The Lausanne study. Lausanne stroke with paradoxal embolism study group. Neurology 1996;46:1301–1305.PubMedGoogle Scholar
  72. 72.
    De Castro S, Cartoni D, Fiorelli M, et al. Morphological and functional characteristics of patent foramen ovale and their embolic implications. Stroke 2000;31:2407–2413.PubMedGoogle Scholar
  73. 73.
    Nedeltchev K, Arnold M, Wahl A, et al. Outcome of patients with cryptogenic stroke and patent foramen ovale. J Neurol Neurosurg Psychiatry 2002;72:347–350.CrossRefPubMedGoogle Scholar
  74. 74.
    Mohr JP, Thompson JL, Lazar RM, et al. A comparison of warfarin and aspirin for the prevention of recurrent ischemic stroke. N Engl J Med 2001;345:1444–1451.CrossRefPubMedGoogle Scholar
  75. 75.
    Homma S, DiTullio MR, Sacco RL, Sciacca RR, Mohr JP. Age as a determinant of adverse events in medically treated cryptogenic stroke patients with patent foramen ovale. Stroke 2004;35:2145–2149.CrossRefPubMedGoogle Scholar
  76. 76.
    Mas JL, Arquizan C, Lamy C, et al. Recurrent cerebrovascular events associated with patent foramen ovale, atrial septal aneurysm, or both. N Engl J Med 2001;345:1740–1746.CrossRefPubMedGoogle Scholar
  77. 77.
    Homma S, Sacco RL, Di Tullio MR, Sciacca RR, Mohr JP. Effect of medical treatment in stroke patients with patent foramen ovale: Patent foramen ovale in cryptogenic stroke study. Circulation 2002;105:2625–2631.CrossRefPubMedGoogle Scholar
  78. 78.
    Furlan AJ. Patent foramen ovale and recurrent stroke: Closure is the best option: Yes. Stroke 2004;35:803–804.CrossRefPubMedGoogle Scholar
  79. 79.
    Landzberg M, Khairy, P. Congenital heart disease: Indications for the closure of patent foramen ovale. Heart 2004;90:219–224.CrossRefPubMedGoogle Scholar
  80. 80.
    Tong DC, Becker KJ. Patent foramen ovale and recurrent stroke: Closure is the best option: No. Stroke 2004;35:804–805.CrossRefPubMedGoogle Scholar
  81. 81.
    Khairy P, O'Donnell CP, Landzberg MJ. Transcatheter closure versus medical therapy of patent foramen ovale and presumed paradoxical thromboemboli: A systematic review. Ann Intern Med 2003;139:753–760.PubMedGoogle Scholar
  82. 82.
    Donnan GA, Davis SM. Patent foramen ovale and stroke: Closure by further randomized trial is required! Stroke 2004;35:806.CrossRefPubMedGoogle Scholar
  83. 83.
    Halperin JL, Fuster V. Patent foramen ovale and recurrent stroke: Another paradoxical twist. Circulation 2002;105:2580–2582.CrossRefPubMedGoogle Scholar
  84. 84.
    Wu LA, Malouf JF, Dearani JA, et al. Patent foramen ovale in cryptogenic stroke: Current understanding and management options. Arch Intern Med 2004;164:950–956.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  1. 1.Department of NeurologyUniversity of ArizonaUSA
  2. 2.Professor of NeurologyArizona Health Science CenterTucson

Personalised recommendations