Infartos cerebrais em pacientes jovens relacionados a deficiência de anticoagulantes naturais proteína C e proteína S

Siqueira Neto, José Ibiapina; Santos, Antonio C.; Fábio, Soraia R. Cabette; Sakamoto, Américo C.

doi:10.1590/S0004-282X1996000400007

Resumos

Infartos cerebrais (IC) em jovens apresentam múltiplas etiologias que diferem do padrão observado nos indivíduos idosos. Deficiências de anticoagulantes naturais têm sido descritas nos últimos anos como causa de IC, principalmente em pacientes com menos de 40 anos. Existe tendência atual de se pesquisar essas deficiências em todos os pacientes jovens com infarto cerebral de causa indeterminada e naqueles com manifestações trombóticas de múltiplos sistemas. Realizamos pesquisa dos níveis de proteína C, proteína S e antitrombina III em pacientes entre 15 e 40 anos com ICs classificados como indeterminados após conclusão de protocolo básico de investigação. Diagnosticamos dois casos de deficiência de proteína C e um caso de deficiência de proteína S. Concluímos que a investigação sistemática de causas hematológicas proporciona decréscimo no número de infartos indeterminados, além de possibilitar a adoção de condutas específicas que diminuem a incidência de novos eventos nos casos diagnosticados.

infarto cerebral; pacientes jovens; proteína C; proteína S; anticoagulantes naturais

The possible etiologies of cerebral infarcts (CI) in young patients differ from those in the older stroke population. Recently, deficiencies of fibrinolytic factors emerged as an important etiology of stroke in the young population. The literature has emphasized the diagnosis of such conditions especially in stroke cases of undetermined etiology and with history of recurrent thrombosis. We carried out a research on the serum level of protein C, protein S, and antithrombin III in young patients, between 15 and 40 years, with CI of undetermined cause after application of a standard protocol. Three patients had low levels of these proteins; two had protein C deficiency, and one protein S deficiency. None of them had antithrombin III deficiency. We conclude that systematic investigation of such causes of cerebral infarct will reduce the group of undetermined strokes, and will open the possibility of prophylactic treatment in a non-negligible group of patients.

cerebral infarct; young patient; protein C deficiency; protein S deficiency

Infartos cerebrais em pacientes jovens relacionados a deficiência de anticoagulantes naturais proteína C e proteína S

Protein C and S deficiencies related stroke in young patients

José Ibiapina Siqueira Neto^I; Antonio C. Santos^II; Soraia R. Cabette Fábio^III; Américo C. Sakamoto^IV

^IM.D., Professor Adjunto Doutor do Departamento de Medicina Clínica da Universidade Federal do Ceará

^IIM.D., Professor Assistente de Neurorradiologia do Departamento de Clínica Médica da Faculdade de Medicina de Ribeirão Preto (FMRP) da Universidade de São Paulo (USP)

^IIIM.D., Médica Assistente do Departamento de Neurologia, Psiquiatria e Psicologia Médica da FMRP/USP

^IVM.D., Professor Associado do Departamento de Neurologia, Psiquiatria e Psicologia Médica da FMRP/USP

RESUMO

Infartos cerebrais (IC) em jovens apresentam múltiplas etiologias que diferem do padrão observado nos indivíduos idosos. Deficiências de anticoagulantes naturais têm sido descritas nos últimos anos como causa de IC, principalmente em pacientes com menos de 40 anos. Existe tendência atual de se pesquisar essas deficiências em todos os pacientes jovens com infarto cerebral de causa indeterminada e naqueles com manifestações trombóticas de múltiplos sistemas. Realizamos pesquisa dos níveis de proteína C, proteína S e antitrombina III em pacientes entre 15 e 40 anos com ICs classificados como indeterminados após conclusão de protocolo básico de investigação. Diagnosticamos dois casos de deficiência de proteína C e um caso de deficiência de proteína S. Concluímos que a investigação sistemática de causas hematológicas proporciona decréscimo no número de infartos indeterminados, além de possibilitar a adoção de condutas específicas que diminuem a incidência de novos eventos nos casos diagnosticados.

Palavras-chave: infarto cerebral, pacientes jovens, proteína C, proteína S, anticoagulantes naturais.

ABSTRACT

The possible etiologies of cerebral infarcts (CI) in young patients differ from those in the older stroke population. Recently, deficiencies of fibrinolytic factors emerged as an important etiology of stroke in the young population. The literature has emphasized the diagnosis of such conditions especially in stroke cases of undetermined etiology and with history of recurrent thrombosis. We carried out a research on the serum level of protein C, protein S, and antithrombin III in young patients, between 15 and 40 years, with CI of undetermined cause after application of a standard protocol. Three patients had low levels of these proteins; two had protein C deficiency, and one protein S deficiency. None of them had antithrombin III deficiency. We conclude that systematic investigation of such causes of cerebral infarct will reduce the group of undetermined strokes, and will open the possibility of prophylactic treatment in a non-negligible group of patients.

Key words: cerebral infarct, young patient, protein C deficiency, protein S deficiency.

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Aceite: 4-junho-1996.

Dr. José Ibiapina Siqueira Neto - Av. Historiador Raimundo Girão 444/701 - 60165-050 Fortaleza CE - Brasil.

1. Adams HP Jr., Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, Marsh EE ID and the TOAST Investigators. Classification of subtype of acute ischemic stroke: definitions for use in a multicenter clinical trial. Stroke 1993;24:35-41.
2. Adams HP Jr., Butler MJ, Biller J, Toffol GJ. Nonhemorrhagic cerebral infarction in young adults. Arch Neurol 1986;43:793-796.
3. Anzola GP, Magoni M, Ascari E, Maffi V. Early prognostic factors in ischemic stroke: the role of protein C and protein S. Stroke 1993;24:1496-1500.
4. Barinagarrementeria F, Cantú-Brito C, de la Peña A, Izaguirre R. Prothrombotic states in young people with idiopatic stroke. Stroke 1994;25:287-290.
5. Barinagarrementeria F, Cantú-Brito C, Izaguirre R, de la Pena. Progressive intracranial occlusive disease associated with deficiency of protein S. Stroke 1993;24:1752-1756.
6. Bevan H, Sharma K, Bradley W. Stroke in young adults. Stroke 1990;21:382-386.
7. Bogousslavsky J, Pierre P. Ischemic stroke in patients under age 45. Neurol Gin 1992; 10:113-124.
8. Chancellor AM, Glasgow GL, Ockelford PA, Johns A, Smith J. Etiology, prognosis, and hemostatic function after cerebral infarction in young adults. Stroke 1989;20:477-482.
9. Cros D, Comp P, Beltran G, Gum G. Superior sagittal sinus thrombosis in a patient with protein S deficiency. Stroke 1990;21:633-636.
10. D'Ângelo A, Landi G, D'Ângelo SV, Orazio EN, Boccardi E, Candelise L, Mannucci PM. Protein C in acute stroke. Stroke 1988;18:579-583.
11. Engesser L, Broekmans AW, Briet E, Brommer EJP, Bertina RM. Hereditary protein S deficiency: clinical manifestations. Ann Intern Med 1987;106:677-682.
12. Green D, Otoya J, Oriba H, Rovner R. Protein S deficiency in middle-aged women with stroke. Neurology 1992;42:1029-1033.
13. Hart RG, Kanter MC. Hematologic disorders and ischemic stroke. Stroke 1990;21:1111-1121.
14. Hart RG, Miller VT. Cerebral infarction in young adults: a praticai approach. Stroke 1983;14:110-114.
15. High KA. Antithrombin III, protein C, and protein S: naturally occurring anticoagulant proteins. Arch Pathol Lab Med 1988;112:28-36.
16. Kazui S, Kuriyama Y, Sakata T, Hiroki M, Miyashita K, Sawada T. Accelerated brain infarction in hypertension complicated by hereditary heterozygous protein C deficiency. Stroke 1993;24:2097-2103.
17. Kilpatrick TJ, Matkovic Z, Davis SM, McGrath CM, Dauer RJ. Hematologic abnormalities occur in both cortical and lacunar infarction. Stroke 1993;24:1945-1950.
18. Kohler J, Kasper J, Witt I, Reutern G-M. Ischemic stroke due to protein C deficiency. Stroke 1990;21:1077-1080.
19. Lagosky W, Witten CM. A case of cerebral infarction in association with free protein S deficiency and oral contraceptive use. Arch Phys Med Rehabil 1993;74:98-100.
20. Martinez HR, Rangel-Guerra RA, Marfil LJ. Ischemic stroke due to deficiency of coagulation inhibitors: report of 10 young adults. Stroke 1993;24:19-25.
21. Matsushita K, Kuriyama Y, Sawada T, Uchida K. Cerebral infaction associated with protein C deficiency. Stroke 1992;23:108-111.
22. Mayer S A, Sacco RL, Hurlet-Jensen A, Shi T, Mohr JP. Free protein S deficiency in acute ischemic stroke. Stroke 1993;24:224-227.
23. Sacco RL, Owen J, Mohr JP, Tatemichi TK, Grossman BA. Free protein S deficiency: a possible association with cerebrovascular occlusion. Stroke 1989;20:1657-1661.
24. Wintzen AR, Broekmans AW, Bertina RM, Briet E, Briet PE, Zecha A, Vielvoye GJ, Bots GThAM. Cerebral haemorrhagic infarction in young patients with hereditary protein C deficiency: evidence for "spontaneous" cerebral venous thrombosis, Br Med J 1985;290:350-352.

Datas de Publicação

Publicação nesta coleção
12 Nov 2010
Data do Fascículo
Dez 1996

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

[1] 1. Adams HP Jr., Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, Marsh EE ID and the TOAST Investigators. Classification of subtype of acute ischemic stroke: definitions for use in a multicenter clinical trial. Stroke 1993;24:35-41.

[2] 2. Adams HP Jr., Butler MJ, Biller J, Toffol GJ. Nonhemorrhagic cerebral infarction in young adults. Arch Neurol 1986;43:793-796.

[3] 3. Anzola GP, Magoni M, Ascari E, Maffi V. Early prognostic factors in ischemic stroke: the role of protein C and protein S. Stroke 1993;24:1496-1500.

[4] 4. Barinagarrementeria F, Cantú-Brito C, de la Peña A, Izaguirre R. Prothrombotic states in young people with idiopatic stroke. Stroke 1994;25:287-290.

[5] 5. Barinagarrementeria F, Cantú-Brito C, Izaguirre R, de la Pena. Progressive intracranial occlusive disease associated with deficiency of protein S. Stroke 1993;24:1752-1756.

[6] 6. Bevan H, Sharma K, Bradley W. Stroke in young adults. Stroke 1990;21:382-386.

[7] 7. Bogousslavsky J, Pierre P. Ischemic stroke in patients under age 45. Neurol Gin 1992; 10:113-124.

[8] 8. Chancellor AM, Glasgow GL, Ockelford PA, Johns A, Smith J. Etiology, prognosis, and hemostatic function after cerebral infarction in young adults. Stroke 1989;20:477-482.

[9] 9. Cros D, Comp P, Beltran G, Gum G. Superior sagittal sinus thrombosis in a patient with protein S deficiency. Stroke 1990;21:633-636.

[10] 10. D'Ângelo A, Landi G, D'Ângelo SV, Orazio EN, Boccardi E, Candelise L, Mannucci PM. Protein C in acute stroke. Stroke 1988;18:579-583.

[11] 11. Engesser L, Broekmans AW, Briet E, Brommer EJP, Bertina RM. Hereditary protein S deficiency: clinical manifestations. Ann Intern Med 1987;106:677-682.

[12] 12. Green D, Otoya J, Oriba H, Rovner R. Protein S deficiency in middle-aged women with stroke. Neurology 1992;42:1029-1033.

[13] 13. Hart RG, Kanter MC. Hematologic disorders and ischemic stroke. Stroke 1990;21:1111-1121.

[14] 14. Hart RG, Miller VT. Cerebral infarction in young adults: a praticai approach. Stroke 1983;14:110-114.

[15] 15. High KA. Antithrombin III, protein C, and protein S: naturally occurring anticoagulant proteins. Arch Pathol Lab Med 1988;112:28-36.

[16] 16. Kazui S, Kuriyama Y, Sakata T, Hiroki M, Miyashita K, Sawada T. Accelerated brain infarction in hypertension complicated by hereditary heterozygous protein C deficiency. Stroke 1993;24:2097-2103.

[17] 17. Kilpatrick TJ, Matkovic Z, Davis SM, McGrath CM, Dauer RJ. Hematologic abnormalities occur in both cortical and lacunar infarction. Stroke 1993;24:1945-1950.

[18] 18. Kohler J, Kasper J, Witt I, Reutern G-M. Ischemic stroke due to protein C deficiency. Stroke 1990;21:1077-1080.

[19] 19. Lagosky W, Witten CM. A case of cerebral infarction in association with free protein S deficiency and oral contraceptive use. Arch Phys Med Rehabil 1993;74:98-100.

[20] 20. Martinez HR, Rangel-Guerra RA, Marfil LJ. Ischemic stroke due to deficiency of coagulation inhibitors: report of 10 young adults. Stroke 1993;24:19-25.

[21] 21. Matsushita K, Kuriyama Y, Sawada T, Uchida K. Cerebral infaction associated with protein C deficiency. Stroke 1992;23:108-111.

[22] 22. Mayer S A, Sacco RL, Hurlet-Jensen A, Shi T, Mohr JP. Free protein S deficiency in acute ischemic stroke. Stroke 1993;24:224-227.

[23] 23. Sacco RL, Owen J, Mohr JP, Tatemichi TK, Grossman BA. Free protein S deficiency: a possible association with cerebrovascular occlusion. Stroke 1989;20:1657-1661.

[24] 24. Wintzen AR, Broekmans AW, Bertina RM, Briet E, Briet PE, Zecha A, Vielvoye GJ, Bots GThAM. Cerebral haemorrhagic infarction in young patients with hereditary protein C deficiency: evidence for "spontaneous" cerebral venous thrombosis, Br Med J 1985;290:350-352.