Ischemic stroke at a young age and thrombophilia caused by deficiency or abnormality of physiological anticoagulants

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Abstract

Arterial and venous thrombosis, primarily acute ischemic stroke is one of the urgent problems of modern neurology. Clinical and pathological analysis revealed heterogeneity of ischemic strokes. At the young age of causes of stroke was significantly different from the causes of stroke in elderly and senile age. In young adults about 1/3 of affiliation to determine the etiologic stroke is not possible. The article focuses on the violations in the system of blood coagulation due to deficiency or abnormality of physiological anticoagulants. We present the clinical features of genetically determinate thrombophilia caused by a deficiency or abnormality of antithrombin III, heparin cofactor II, protein C, protein S, protein Z, and thrombomodulin. It is shown that the incidence of these conditions in the general population and in patients with arterial and venous thrombosis. We present diagnostic techniques.

About the authors

N. V Pizova

Yaroslavl State Medical University of the Ministry of Health of the Russian Federation

Email: pizova@yndex.ru
д-р мед. наук, проф. каф. нервных болезней с медицинской генетикой и нейрохирургией ГБОУ ВПО ЯГМУ 150000, Russian Federation, Yaroslavl, ul. Revoliutsionnaia, d. 5

References

  1. Franchini M, Veneri D. Inherited thrombophilia: an update. Clin Lab 2005; 51: 357-65.
  2. Nachman R.L, Silverstein R. Hypercoagulable states. Ann Intern Med 1993; 119: 819-7.
  3. Schafer A.I. The hypercoagulable states. Ann Intern Med 1985; 102: 814-28.
  4. Jordan F.L.J, Nandorff A. The familial tendency in thromboembolic disease. Acta Med Scand 1956; 156: 267-75.
  5. Egeberg O. Inherited antithrombin deficiency causing thrombophilia. Thromb Diath Haemorgh 1965; 13: 516-30.
  6. Egeberg O. Proceedings: Inherited antithrombin III deficiency and thromboembolism. Thromb Diath Haemorgh 1975; 34: 366.
  7. Manucci P.M. The molecular basis of inherited thrombophilia. Vox Sang 2000; 78: 39-5.
  8. Сушкевич Г.Н. Тромбогенерирующие системы при тромбофилиях различного генеза. Лаб. мед. 2009; 10: 11-22.
  9. Патрушев Л.И. Тромбофилические состояния и современные методы их диагностики. РМЖ. 1998; 6 (3): 181-5.
  10. Васильев С.А., Виноградов В.Л., Гемджян Э.Г. и др. Сочетанные генетические и приобретенные формы тромбофилий. 4-я Всерос. конф. «Клиническая гемостазиология в сердечно - сосудистой хирургии» (с международным участием). М.: НЦССХ им. А.Н.Бакулева, 2009; с. 84-5.
  11. Barinagarrementeria F, Cantu-Brito C, De La Pena A, Izaguirre R. Prothrombotic states in young people with idiopathic stroke. A prospective study. Stroke 1994; 25 (2): 287-90.
  12. Bock S, Harris J, Balazs I, Trent J. Assignment of the human antithrombin III structural gene to chromosome 1q23-25. Cytogenet Cell Genet 1985; 39: 67-9.
  13. Kobelt K, Biasiutti F.D, Mattle H.P et al. Protein Z in ischaemic stroke. Br J Haematol 2001; 114: 169-73.
  14. Spek C.A, Reitsma P.H. Genetic risk factors for venous thrombosis. Mol Genet Metab 2000; 71: 51-61.
  15. Lane D.A, Olds R.J, Boisclair M et al. Antithrombin III mutation database: first update. For the Thrombin and its Inhibitors Subcommittee of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Thromb Haemost 1993; 70 (2): 361-9.
  16. Lane D, Bayston T, Olds R et al. Antithrombin mutation database: 2nd (1997) update. For the Plasma Coagulation Inhibitors Subcommittee of the Scientific and Standardisation Committee of the International Society on Thrombosis and Haemostasis. Thromb Haemost 1997; 77: 197-211.
  17. Лагутина Н.Я., Федулова Г.А. Антитромбин III. Обзор. Пробл. гематологии. 1982; 3: 42-50.
  18. Thaler E, Lechner K. Antithrombin III deficiency and thromboembolism. Clin Haematol 1981; 10 (2): 369-90.
  19. Martinelli I, Mannucci P.M, De Stefano V et al. Different risks of thrombosis in four coagulation defects associated with inherited thrombophilia: a study of 150 families. Blood 1998; 92 (7): 2353-8.
  20. Simioni P, Sanson B.J, Prandoni P et al. Incidence of venous thromboembolism in families with inherited thrombophilia. Thromb Haemost 1999; 81 (2): 198-202.
  21. Tait R.C, Walker I.D, Perry D.J et al. Prevalence of antithrombin deficiency in the healthy population. Br J Haematol 1994; 87 (1): 106-12.
  22. Moster M. Coagulopathies and arterial stroke. J Neuro-Ophthalmol 2003; 23 (1): 63-71.
  23. Tollefsen D.M, Majerus D.W, Blank M.K. Heparin cofactor II. Purification and properties of a heparin - dependent inhibitor of thrombin in human plasma. J Biol Chem 1982; 257 (5): 2162-9.
  24. Tollefsen D.M. Heparin cofactor II modulates the response to vascular injury. Arterioscler Thromb Vasc Biol 2007; 27: 454-60.
  25. Tollefsen D.M. Heparin cofactor II deficiency. Arch Pathol Lab Med 2002; 126: 1394-400.
  26. Schwarz H.P, Fischer M, Hopmeier P et al. Plasma protein S deficiency in familial thrombotic disease. Blood 1984; 64 (6): 1297-300.
  27. Tran T.H, Duckert F. Influence of heparin cofactor II (HCII) on the determination of antithrombin III (AT). Thromb Res. 1985; 40 (4): 571-6.
  28. Huntington J.A, Kjellberg M, Stenflo J. Crystal structure of protein C inhibitor provides insights into hormone binding and heparin activation. Structure 2003; 11: 205-15.
  29. Dhainaut J-F, Yan В, Cariou A, Mira J-P. Soluble thrombomodulin, plasma - derived unactivated protein C, and recombinant human activated protein С in sepsis. Crit Care Med 2002; 30: 318-24.
  30. Esmon C. The protein С pathway. Crit Care Med 2000; 28: 44-8.
  31. Pike R.N, Buckle A.M, le Bonniec B.F, Church F.C. Control of the coagulation system by serpins. Getting by with a little help from glycosaminoglycans. FEBS J 2005; 272: 4842-51.
  32. Aznar J, Espana F, Estelles A, Royo M. Heparin stimulation of the inhibition of activated protein C and other enzymes by human protein C inhibitor - influence of the molecular weight of heparin and ionic strength. Thromb Haemost 1996; 76: 983-8.
  33. Dahlback B, Carlsson M, Svensson P.J. Familial thrombophilia due to a previously unrecognized mechanism characterized by poor anticoagulant response to activated protein C: prediction of a cofactor to activated protein C. Proc Natl Acad Sci USA 1993; 90 (3): 1004-8.
  34. Bertina R.M, Broekmans A.W, van der Linden I.K, Mertens K. Protein C deficiency in a Dutch family with thrombotic disease. Thromb Haemost 1982; 48 (1): 1-5.
  35. Bertina R.M, Broekmans A.W, Krommenhoek van Es C, van Wijngaarden A. The use of a functional and immunologic assay for plasma protein C in the study of the heterogeneity of congenital protein C deficiency. Thromb Haemost 1984; 51 (1): 1-5.
  36. Comp P.C, Nixon R.R, Esmon C.T. Determination of functional levels of protein C, an antithrombotic protein, using thrombin - thrombomodulin complex. Blood 1984; 63 (1): 15-21.
  37. Comp P.C, Esman C.T. Recurrent venous thromboembolism in patients with a partial deficiency of protein C. N Engl J Med 1984; 311 (24): 1525-28.
  38. Patracchini P, Aiello V, Palazzi P et al. Sublocalization of the human protein C gene on chromosome 2q13-q14. Hum Genet 1989; 81 (2): 191-2.
  39. De Stefano V, Rossi E, Paciaroni K, Leone G. Screening for inherited thrombophilia: indications and therapeutic implications. Haematologica 2002; 87: 1095-108.
  40. Griffin J.H, Evatt B, Zimmermann T.S et al. Deficiency of protein C in congenital thrombotic disease. J Clin Invest 1981; 68: 1370-73.
  41. Pabinger J, Kurie P.A, Heistinger M et al. The risc of thromboembolism in asymptomatic patients with protein C and protein S debiciencg. Thromb Haemost 1994; 71: 441-5.
  42. Miletich J.P, Sherman L, Broze G.J.J. Absence of thrombosis in subjects with heterozygous protein C deficiency. N Engl J Med 1987; 317: 991-6.
  43. Griffin J.H. Clinical studies of protein C. Semin Thromb Hemost 1984; 10 (2): 162-6.
  44. Tait R.C, Walker I.D, Reitsma P.H et al. Prevalence of protein C deficiency in the healthy population. Thromb Haemost 1995; 73 (1): 87-93.
  45. Meijer-Huizinga F, Mertens K, van Mourik J.A. Isolation and characterization of single - chain protein S. Thromb Haemost 1994; 72 (3): 408-14.
  46. Walker F.J. Regulation of activated protein C by a new protein. A possible function for bovine protein S. J Biol Chem 1980; 255 (12): 5521-4.
  47. Walker F.J. Regulation of activated protein C by protein S. The role of phospholipid in factor Va inactivation. J Biol Chem 1981; 256 (21): 11128-31.
  48. Walker F.J, Chavin S.I, Fay P.J. Inactivation of factor VIII by activated protein C and protein S. Arch Biochem Biophys 1987; 252 (1): 322-8.
  49. Schwarz H.P, Fischer M, Hopmeier P et al. Plasma protein S deficiency in familial thrombotic disease. Blood 1984; 64 (6): 1297-300.
  50. Allaart C.F, Aronson D.C, Ruys T et al. Hereditary protein S deficiency in young adults with arterial occlusive disease. Thromb Haemost 1990; 64 (2): 206-10.
  51. Broekmans A.W, Bertina R.M, Reinalda-Poot J et al. Hereditary protein S deficiency and venous thrombo - embolism. A study in three Dutch families. Thromb Haemost 1985; 53 (2): 273-7.
  52. Makris M, Leach M, Beauchamp N.J et al. Genetic analysis, phenotypic diagnosis, and risk of venous thrombosis in families with inherited deficiencies of protein S. Blood 2000; 95 (6): 1935-41.
  53. Long G.L, Marshall A, Gardner J.C, Naylor S.L. Genes for human vitamin K-dependent plasma proteins C and S are located on chromosomes 2 and 3, respectively. Somat Cell Mol Genet 1988; 14 (1): 93-8.
  54. Watkins P.C, Eddy R, Beck A.K et al. DNA sequence and regional assignment of the human follicle - stimulating hormone beta - subunit gene to the short arm of human chromosome 11. DNA 1987; 6 (3): 205-12.
  55. Watkins P.C, Eddy R, Fukushima Y et al. The gene for protein S maps near the centromere of human chromosome 3. Blood 1988; 71 (1): 238-41.
  56. Engesser L, Broekmans A.W, Briet E et al. Hereditary protein S deficiency: clinical manifestations. Ann Intern Med 1987; 106 (5): 677-82.
  57. Girolami A, Simioni P, Lazzaro A.R, Cordiano I. Severe arterial cerebral thrombosis in a patient with protein S deficiency (moderately reduced total and markedly reduced free protein S): a family study. Thromb Haemost 1989; 61 (1): 144-7.
  58. Sie P, Boneu B, Bierme R et al. Arterial thrombosis and protein S deficiency. Thromb Haemost 1989; 62 (3): 1040.
  59. Wiesel M.L, Borg J.Y, Grunebaum L et al. Influence of protein S deficiency on the arterial thrombosis risk. Presse Med 1991; 20 (22): 1023-7.
  60. Douay X, Lucas C, Caron C et al. Antithrombin, protein C and protein S levels in 127 consecutive young adults with ischemic stroke. Acta Neurol Scand 1998; 98 (2): 124-7.
  61. Mayer S.A, Sacco R.L, Hurlet-Jensen A et al. Free protein S deficiency in acute ischemic stroke. A case - control study. Stroke 1993; 24 (2): 224-7.
  62. Broze G.J, Miletich J.P. Human protein Z. J Clin Invest 1984; 73: 933-38.
  63. Hogg P.J, Stenflo J. Interaction of vitamin K-dependent protein Z with thrombin. J Biol Chem 1990; 266: 1053-58.
  64. Hogg P.J, Stenflo J. Interaction of human protein Z with thrombin: evaluation of the species difference in the interaction between bovine and human protein Z and thrombin. Biochem Biophys Res Commun 1991; 178: 801-7.
  65. Kempkes-Matthes B, Walmrath D, Matthes K.J. Protein Z deficiency: a new cause of bleeding tendency. Thromb Res 1995; 79: 49-55.
  66. Broze G.J.Jr. Protein Z dependent regulation of coagulation. Thromb Haemost 2001; 86: 8-13.
  67. Kemkes-Matthes B, Souri M, Ichinose A, Matthes K.J. First cases of homozygous combined protein Z- and factor V Leiden - mutation in humans. Blood 2000; 96: 74b. Abstract.
  68. Kemkes-Matthes B, Nees M, Kuhnel G et al. Protein Z influences prothrombotic phenotype of factor V Leiden in humans. Thromb Res 2002; 106: 183-85.
  69. Mc Quillan A.M, Eikelboom J.W, Hankey G.J et al. Protein Z in ischemic stroke and its etiologic subtypes. Stroke 2003; 34: 2415-19.
  70. Fujimaki K, Yamazaki T, Taniwaki M, Ichinose A. The gene for human protein Z is localized to chromosome 13 at band q34 and is coded by eight regular exons and one alternative exon. Biochemistry 1998; 37: 6838-46.
  71. Vasse M, Guegan-Massardier E, Borg J.Y et al. Frequency of protein Z deficiency in patients with ischaemic stroke. Lancet 2001; 357: 933-34.
  72. Heeb M.J, Paganini-Hill A, Griffin J.H, Fischer M. Low protein Z levels and risk of ischaemic stroke: differences by diabetic status and gender. Blood Cells Mol Dis 2002; 29: 139-44.
  73. Lopaciuk S, Bykowska K, Kwiecinski H et al. Protein Z in young survivors of ischaemic stroke. Thromb Haemost 2002; 88: 536.
  74. Личи К, Кропп С, Донг-Си Т и др. Уровень протеина Z в плазме и риск развития ишемии головного мозга у молодых лиц зависят от варианта полиморфизма гена, кодирующего этот белок. Stroke. Российское издание. 2004; 5: 64-70.
  75. Bird P. Thrombomodulin. Haematol Rev 1996; 9: 251-74.
  76. Кудряшева О.В., Затейщиков Д.А., Сидоренко Б.А. Эндотелиальный гемостаз: система тромбомодулина и ее роль в развитии атеросклероза и его осложнений. Кардиология. 2000; 40 (8): 65-70.
  77. Bushnell C.D, Goldstein L.B. Diagnostic testing for coagulopathies in patients with ischemic stroke. Stroke 2000; 31: 3067-78.
  78. Carod-Artal F.J, Nunes S.V, Portugal D et al. Ischemic stroke subtypes and thrombophilia in young and elderly Brazilian stroke patients admitted to a rehabilitation hospital. Stroke 2005; 36 (9): 2012-4.
  79. Ranzan J, Rotta N.T. Ischemic stroke in children: a study of the associated alterations. Arq Neuropsiquiatr 2004; 62 (3A): 618-25.
  80. Hellgren M, Svensson P.J, Dahlback B. Resistance to activated protein C as a basis for venous thromboembolism associated with pregnancy and contraceptives. Am J Obstet Gynecol 1995; 173: 210-13.
  81. Gandrille S, Greengard J.S, Alhenc-Gelas M et al. Incidence of activated protein C resistance caused by the ARG 506 GLN mutation in factor V in 113 unrelated symptomatic protein C-deficient patients. The French Network on the behalf of INSERM. Blood 1995; 86: 219-24.
  82. Zoller B, Berntsdotter A, Garcia de Frutos P, Dahlback B. Resistance to activated protein C as an additional genetic risk factor in hereditary deficiency of protein S. Blood 1995; 85: 3518-23.
  83. Alhenc-Gelas M, Aiach M, de Moerloose P. Venous thromboembolic disease: risk factors and laboratory investigation. Semin Vasc Med 2001; 1 (1): 81-8.
  84. Varnai K, Gutler F, Szekely E. Hemorheological parameters in patients with thrombophilia. Biorheology 1999; 1-2: 148.

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