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Ишемический инсульт в молодом возрасте и тромбофилии, обусловленные дефицитом или аномалиями физиологических антикоагулянтов
Пизова Н.В. Ишемический инсульт в молодом возрасте и тромбофилии, обусловленные дефицитом или аномалиями физиологических антикоагулянтов. Consilium Medicum. 2015; 17 (9): 21–26. DOI: 10.26442/2075-1753_2015.9.21-26
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Pizova N.V. Ischemic stroke at a young age and thrombophilia caused by deficiency or abnormality of physiological anticoagulants. Consilium Medicum. 2015; 17 (9): 21–26. DOI: 10.26442/2075-1753_2015.9.21-26
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Аннотация
Артериальные и венозные тромбозы и в первую очередь острые нарушения мозгового кровообращения являются одной из актуальных проблем современной неврологии. Клинический и патоморфологический анализ показал гетерогенность ишемических инсультов. В молодом возрасте причины развития острых нарушений мозгового кровообращения значимо отличаются от причин инсультов в пожилом и старческом возрасте. У лиц молодого возраста примерно в 1/3 случаев определить этиологическую принадлежность инсульта не представляется возможным. В статье основное внимание уделено нарушениям в системе свертывания крови, обусловленным дефицитом или аномалиями физиологических антикоагулянтов. Представлены клинические особенности генетически детерминируемых тромбофилий, вызванных дефицитом или аномалиями антитромбина III, кофактора гепарина II, протеина С, протеина S, протеина Z и тромбомодулина. Показана частота встречаемости данных состояний как в общей популяции, так и у лиц с артериальными и венозными тромбозами. Представлены диагностические методики.
Ключевые слова: тромбофилия, дефицит или аномалия физиологических антикоагулянтов, инсульты в молодом возрасте.
Ключевые слова: тромбофилия, дефицит или аномалия физиологических антикоагулянтов, инсульты в молодом возрасте.
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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.
Key words: thrombophilia, a deficiency or abnormality of physiological anticoagulants stroke at a young age.
Key words: thrombophilia, a deficiency or abnormality of physiological anticoagulants stroke at a young age.
Полный текст
Список литературы
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3. Schafer AI. The hypercoagulable states. Ann Intern Med 1985; 102: 814–28.
4. Jordan FLJ, 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 PM. 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. / Sushkevich G.N. Trombogeneriruiushchie sistemy pri trombofiliiakh razlichnogo geneza. Lab. med. 2009; 10: 11–22. [in Russian]
9. Патрушев Л.И. Тромбофилические состояния и современные методы их диагностики. РМЖ. 1998; 6 (3): 181–5. / Patrushev L.I. Trombofilicheskie sostoianiia i sovremennye metody ikh diagnostiki. RMZh. 1998; 6 (3): 181–5. [in Russian]
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. / Vasil'ev S.A., Vinogradov V.L., Gemdzhian E.G. i dr. Sochetannye geneticheskie i priobretennye formy trombofilii. 4-ia Vseros. konf. «Klinicheskaia gemostaziologiia v serdechno-sosudistoi khirurgii» (s mezhdunarodnym uchastiem). M.: NTsSSKh im. A.N.Bakuleva, 2009; s. 84–5. [in Russian]
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 FD, Mattle HP et al. Protein Z in ischaemic stroke. Br J Haematol 2001; 114: 169–73.
14. Spek CA, Reitsma PH. Genetic risk factors for venous thrombosis. Mol Genet Metab 2000; 71: 51–61.
15. Lane DA, Olds RJ, 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. / Lagutina N.Ia., Fedulova G.A. Antitrombin III. Obzor. Probl. gematologii. 1982; 3: 42–50. [in Russian]
18. Thaler E, Lechner K. Antithrombin III deficiency and thromboembolism. Clin Haematol 1981; 10 (2): 369–90.
19. Martinelli I, Mannucci PM, 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 BJ, Prandoni P et al. Incidence of venous thromboembolism in families with inherited thrombophilia. Thromb Haemost 1999; 81 (2): 198–202.
21. Tait RC, Walker ID, Perry DJ 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 DM, Majerus DW, Blank MK. 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 DM. Heparin cofactor II modulates the response to vascular injury. Arterioscler Thromb Vasc Biol 2007; 27: 454–60.
25. Tollefsen DM. Heparin cofactor II deficiency. Arch Pathol Lab Med 2002; 126: 1394–400.
26. Schwarz HP, Fischer M, Hopmeier P et al. Plasma protein S deficiency in familial thrombotic disease. Blood 1984; 64 (6): 1297–300.
27. Tran TH, Duckert F. Influence of heparin cofactor II (HCII) on the determination of antithrombin III (AT). Thromb Res. 1985; 40 (4): 571–6.
28. Huntington JA, 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 RN, Buckle AM, le Bonniec BF, Church FC. 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 PJ. 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 RM, Broekmans AW, van der Linden IK, Mertens K. Protein C deficiency in a Dutch family with thrombotic disease. Thromb Haemost 1982; 48 (1): 1–5.
35. Bertina RM, Broekmans AW, 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 PC, Nixon RR, Esmon CT. Determination of functional levels of protein C, an antithrombotic protein, using thrombin-thrombomodulin complex. Blood 1984; 63 (1): 15–21.
37. Comp PC, Esman CT. 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 JH, Evatt B, Zimmermann TS et al. Deficiency of protein C in congenital thrombotic disease. J Clin Invest 1981; 68: 1370–73.
41. Pabinger J, Kurie PA, 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 JP, Sherman L, Broze GJJ. Absence of thrombosis in subjects with heterozygous protein C deficiency. N Engl J Med 1987; 317: 991–6.
43. Griffin JH. Clinical studies of protein C. Semin Thromb Hemost 1984; 10 (2): 162–6.
44. Tait RC, Walker ID, Reitsma PH 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 JA. Isolation and characterization of single-chain protein S. Thromb Haemost 1994; 72 (3): 408–14.
46. Walker FJ. 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 FJ. 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 FJ, Chavin SI, Fay PJ. Inactivation of factor VIII by activated protein C and protein S. Arch Biochem Biophys 1987; 252 (1): 322–8.
49. Schwarz HP, Fischer M, Hopmeier P et al. Plasma protein S deficiency in familial thrombotic disease. Blood 1984; 64 (6): 1297–300.
50. Allaart CF, Aronson DC, Ruys T et al. Hereditary protein S deficiency in young adults with arterial occlusive disease. Thromb Haemost 1990; 64 (2): 206–10.
51. Broekmans AW, Bertina RM, 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 NJ 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 GL, Marshall A, Gardner JC, Naylor SL. 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 PC, Eddy R, Beck AK 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 PC, 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 AW, Briet E et al. Hereditary protein S deficiency: clinical manifestations. Ann Intern Med 1987; 106 (5): 677–82.
57. Girolami A, Simioni P, Lazzaro AR, 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 ML, Borg JY, 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 SA, Sacco RL, 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 GJ, Miletich J.P. Human protein Z. J Clin Invest 1984; 73: 933–38.
63. Hogg PJ, Stenflo J. Interaction of vitamin K-dependent protein Z with thrombin. J Biol Chem 1990; 266: 1053–58.
64. Hogg PJ, 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 KJ. Protein Z deficiency: a new cause of bleeding tendency. Thromb Res 1995; 79: 49–55.
66. Broze GJJr. Protein Z dependent regulation of coagulation. Thromb Haemost 2001; 86: 8–13.
67. Kemkes-Matthes B, Souri M, Ichinose A, Matthes KJ. 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. McQuillan AM, Eikelboom JW, Hankey GJ 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 JY et al. Frequency of protein Z deficiency in patients with ischaemic stroke. Lancet 2001; 357: 933–34.
72. Heeb MJ, Paganini-Hill A, Griffin JH, 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. / Lichi K, Kropp S, Dong-Si T i dr. Uroven' proteina Z v plazme i risk razvitiia ishemii golovnogo mozga u molodykh lits zavisiat ot varianta polimorfizma gena, kodiruiushchego etot belok. Stroke. Rossiiskoe izdanie. 2004; 5: 64–70. [in Russian]
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. / Kudriasheva O.V., Zateishchikov D.A., Sidorenko B.A. Endotelial'nyi gemostaz: sistema trombomodulina i ee rol' v razvitii ateroskleroza i ego oslozhnenii. Kardiologiia. 2000; 40 (8): 65–70. [in Russian]
77. Bushnell CD, Goldstein LB. Diagnostic testing for coagulopathies in patients with ischemic stroke. Stroke 2000; 31: 3067–78.
78. Carod-Artal FJ, Nunes SV, 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 NT. Ischemic stroke in children: a study of the associated alterations. Arq Neuropsiquiatr 2004; 62 (3A): 618–25.
80. Hellgren M, Svensson PJ, 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 JS, 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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35. Bertina RM, Broekmans AW, 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.
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37. Comp PC, Esman CT. 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 JH, Evatt B, Zimmermann TS et al. Deficiency of protein C in congenital thrombotic disease. J Clin Invest 1981; 68: 1370–73.
41. Pabinger J, Kurie PA, 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 JP, Sherman L, Broze GJJ. Absence of thrombosis in subjects with heterozygous protein C deficiency. N Engl J Med 1987; 317: 991–6.
43. Griffin JH. Clinical studies of protein C. Semin Thromb Hemost 1984; 10 (2): 162–6.
44. Tait RC, Walker ID, Reitsma PH 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 JA. Isolation and characterization of single-chain protein S. Thromb Haemost 1994; 72 (3): 408–14.
46. Walker FJ. 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 FJ. 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 FJ, Chavin SI, Fay PJ. Inactivation of factor VIII by activated protein C and protein S. Arch Biochem Biophys 1987; 252 (1): 322–8.
49. Schwarz HP, Fischer M, Hopmeier P et al. Plasma protein S deficiency in familial thrombotic disease. Blood 1984; 64 (6): 1297–300.
50. Allaart CF, Aronson DC, Ruys T et al. Hereditary protein S deficiency in young adults with arterial occlusive disease. Thromb Haemost 1990; 64 (2): 206–10.
51. Broekmans AW, Bertina RM, 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 NJ 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 GL, Marshall A, Gardner JC, Naylor SL. 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 PC, Eddy R, Beck AK 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 PC, 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 AW, Briet E et al. Hereditary protein S deficiency: clinical manifestations. Ann Intern Med 1987; 106 (5): 677–82.
57. Girolami A, Simioni P, Lazzaro AR, 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 ML, Borg JY, 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 SA, Sacco RL, 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 GJ, Miletich J.P. Human protein Z. J Clin Invest 1984; 73: 933–38.
63. Hogg PJ, Stenflo J. Interaction of vitamin K-dependent protein Z with thrombin. J Biol Chem 1990; 266: 1053–58.
64. Hogg PJ, 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 KJ. Protein Z deficiency: a new cause of bleeding tendency. Thromb Res 1995; 79: 49–55.
66. Broze GJJr. Protein Z dependent regulation of coagulation. Thromb Haemost 2001; 86: 8–13.
67. Kemkes-Matthes B, Souri M, Ichinose A, Matthes KJ. 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. McQuillan AM, Eikelboom JW, Hankey GJ 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 JY et al. Frequency of protein Z deficiency in patients with ischaemic stroke. Lancet 2001; 357: 933–34.
72. Heeb MJ, Paganini-Hill A, Griffin JH, 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. Lichi K, Kropp S, Dong-Si T i dr. Uroven' proteina Z v plazme i risk razvitiia ishemii golovnogo mozga u molodykh lits zavisiat ot varianta polimorfizma gena, kodiruiushchego etot belok. Stroke. Rossiiskoe izdanie. 2004; 5: 64–70. [in Russian]
75. Bird P. Thrombomodulin. Haematol Rev 1996; 9: 251–74.
76. Kudriasheva O.V., Zateishchikov D.A., Sidorenko B.A. Endotelial'nyi gemostaz: sistema trombomodulina i ee rol' v razvitii ateroskleroza i ego oslozhnenii. Kardiologiia. 2000; 40 (8): 65–70. [in Russian]
77. Bushnell CD, Goldstein LB. Diagnostic testing for coagulopathies in patients with ischemic stroke. Stroke 2000; 31: 3067–78.
78. Carod-Artal FJ, Nunes SV, 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 NT. Ischemic stroke in children: a study of the associated alterations. Arq Neuropsiquiatr 2004; 62 (3A): 618–25.
80. Hellgren M, Svensson PJ, 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 JS, 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.
Авторы
Н.В.Пизова
ГБОУ ВПО Ярославский государственный медицинский университет Минздрава России. 150000, Россия, Ярославль, ул. Революционная, д. 5
pizova@yndex.ru
ГБОУ ВПО Ярославский государственный медицинский университет Минздрава России. 150000, Россия, Ярославль, ул. Революционная, д. 5
pizova@yndex.ru
________________________________________________
N.V.Pizova
Yaroslavl State Medical University of the Ministry of Health of the Russian Federation. 150000, Russian Federation, Yaroslavl, ul. Revoliutsionnaia, d. 5
pizova@yndex.ru
Yaroslavl State Medical University of the Ministry of Health of the Russian Federation. 150000, Russian Federation, Yaroslavl, ul. Revoliutsionnaia, d. 5
pizova@yndex.ru
Цель портала OmniDoctor – предоставление профессиональной информации врачам, провизорам и фармацевтам.