妊娠初期にプロテインS欠乏症と妊娠時一過性甲状腺機能亢進症を契機に発症した脳静脈洞血栓症の治療中にヘパリンアレルギーを来した1例
症例は30歳女性．妊娠6週の悪阻出現後，7週に頭痛，8週に右片麻痺を認めた．意識はJCS-1で，右半側空間無視と右片麻痺を認めた．頭部MRI/MRVにて脳静脈洞血栓症と診断した．血液検査から，プロテインS欠乏症と妊娠時一過性甲状腺機能亢進症が原因と考えられた．ヘパリン持続投与にて神経・画像所見は改善した．妊娠11週からヘパリン皮下注に変更した．妊娠27週に注射部位に一致した硬結と掻痒を伴う紅斑が出現し，同薬による遅発性過敏反応と診断した．ヘパリン減量，注射部位変更，ステロイド剤外用にて治療を継続した．妊娠38週に経腟分娩で出産したが，母子共に問題はなかった．産後46日でヘパリンを中止したが，血...
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| Published in | 脳卒中 Vol. 45; no. 1; pp. 56 - 62 |
|---|---|
| Main Authors | , , , , , , , , |
| Format | Journal Article |
| Language | Japanese |
| Published |
一般社団法人 日本脳卒中学会
2023
日本脳卒中学会 |
| Subjects | |
| Online Access | Get full text |
| ISSN | 0912-0726 1883-1923 |
| DOI | 10.3995/jstroke.11051 |
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| Abstract | 症例は30歳女性．妊娠6週の悪阻出現後，7週に頭痛，8週に右片麻痺を認めた．意識はJCS-1で，右半側空間無視と右片麻痺を認めた．頭部MRI/MRVにて脳静脈洞血栓症と診断した．血液検査から，プロテインS欠乏症と妊娠時一過性甲状腺機能亢進症が原因と考えられた．ヘパリン持続投与にて神経・画像所見は改善した．妊娠11週からヘパリン皮下注に変更した．妊娠27週に注射部位に一致した硬結と掻痒を伴う紅斑が出現し，同薬による遅発性過敏反応と診断した．ヘパリン減量，注射部位変更，ステロイド剤外用にて治療を継続した．妊娠38週に経腟分娩で出産したが，母子共に問題はなかった．産後46日でヘパリンを中止したが，血栓症や皮膚所見の再燃はない．今後，再妊娠時において，抗凝固療法は必要となる可能性が高いと予測されるため，胎盤・母乳移行や催奇形性を考慮した，慎重な代替薬の選択が必要である． |
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| AbstractList | 症例は30歳女性．妊娠6週の悪阻出現後，7週に頭痛，8週に右片麻痺を認めた．意識はJCS-1で，右半側空間無視と右片麻痺を認めた．頭部MRI/MRVにて脳静脈洞血栓症と診断した．血液検査から，プロテインS欠乏症と妊娠時一過性甲状腺機能亢進症が原因と考えられた．ヘパリン持続投与にて神経・画像所見は改善した．妊娠11週からヘパリン皮下注に変更した．妊娠27週に注射部位に一致した硬結と掻痒を伴う紅斑が出現し，同薬による遅発性過敏反応と診断した．ヘパリン減量，注射部位変更，ステロイド剤外用にて治療を継続した．妊娠38週に経腟分娩で出産したが，母子共に問題はなかった．産後46日でヘパリンを中止したが，血栓症や皮膚所見の再燃はない．今後，再妊娠時において，抗凝固療法は必要となる可能性が高いと予測されるため，胎盤・母乳移行や催奇形性を考慮した，慎重な代替薬の選択が必要である． 要旨:症例は30歳女性. 妊娠6週の悪阻出現後, 7週に頭痛, 8週に右片麻痺を認めた. 意識はJCS-1で, 右半側空間無視と右片麻痺を認めた. 頭部MRI/MRVにて脳静脈洞血栓症と診断した. 血液検査から, プロテインS欠乏症と妊娠時一過性甲状腺機能亢進症が原因と考えられた. ヘパリン持続投与にて神経・画像所見は改善した. 妊娠11週からヘパリン皮下注に変更した. 妊娠27週に注射部位に一致した硬結と掻痒を伴う紅斑が出現し, 同薬による遅発性過敏反応と診断した. ヘパリン減量, 注射部位変更, ステロイド剤外用にて治療を継続した. 妊娠38週に経腟分娩で出産したが, 母子共に問題はなかった. 産後46日でヘパリンを中止したが, 血栓症や皮膚所見の再燃はない. 今後, 再妊娠時において, 抗凝固療法は必要となる可能性が高いと予測されるため, 胎盤・母乳移行や催奇形性を考慮した, 慎重な代替薬の選択が必要である. |
| Author | 奥津, 武志 京樂, 格 久保, 仁 上田, 彩加 玉井, 宏一 渡部, 真志 岡本, 憲省 烏谷, 政和 尾上, 裕貴 |
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| References | 7） Gilabert J, Fernandez JA, España F, et al.: Physiological coagulation inhibitors (protein S, protein C and antithrombin III) in severe preeclamptic states and in users of oral contraceptives. Thromb Res 49: 319–329, 1988 11） Alfirevic Z, Roberts D, Martlew V: How strong is the association between maternal thrombophilia and adverse pregnancy outcome? A systematic review. Eur J Obstet Gynecol Reprod Biol 101: 6–14, 2002 19） Weberschock T, Meister AC, Bohrt K, et al.: The risk for cross-reactions after a cutaneous delayed-type hypersensitivity reaction to heparin preparations is independent of their molecular weight: a systematic review. Contact Dermatitis 65: 187–194, 2011 10） Malm J, Laurell M, Dahlbäck B: Changes in the plasma levels of vitamin K-dependent proteins C and S and of C4b-binding protein during pregnancy and oral contraception. Br J Haematol 68: 437–443, 1988 14） Goldman AM, Mestman JH: Transient non-autoimmune hyperthyroidism of early pregnancy. J Thyroid Res 2011: 142413, 2011 15） Debeij J, van Zaane B, Dekkers OM, et al.: High levels of procoagulant factors mediate the association between free thyroxine and the risk of venous thrombosis: the MEGA study. J Thromb Haemost 12: 839–846, 2014 6） Liang ZW, Gao WL, Feng LM: Clinical characteristics and prognosis of cerebral venous thrombosis in Chinese women during pregnancy and puerperium. Sci Rep 7: 43866, 2017 13） Albaar MT, Adam JM: Gestational transient thyrotoxicosis. Acta Med Indones 41: 99–104, 2009 20） Mazzolai L, Hohlfeld P, Spertini F, et al.: Fondaparinux is a safe alternative in case of heparin intolerance during pregnancy. Blood 108: 1569–1570, 2006 12） Shen MC, Wu WJ, Cheng PJ, et al.: Low-molecular-weight-heparin can benefit women with recurrent pregnancy loss and sole protein S deficiency: a historical control cohort study from Taiwan. Thromb J 14: 44, 2016 5） 赤澤宗俊，東條伸平，権丈洋徳ら：妊娠に伴う脳静脈洞血栓症について：自験例を含む本邦73例の文献的検討．日周産期・新生児会誌 48: 87–94, 2012 8） Comp PC, Thurnau GR, Welsh J, et al.: Functional and immunologic protein S levels are decreased during pregnancy. Blood 68: 881–885, 1986 2） Ferro JM, Canhão P, Stam J, et al.: Prognosis of cerebral vein and dural sinus thrombosis: results of the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT). Stroke 35: 664–670, 2004 3） Cantú C, Barinagarrementeria F: Cerebral venous thrombosis associated with pregnancy and puerperium. Review of 67 cases. Stroke 24: 1880–1884, 1993 18） Hassouna A, Allam H: Limited dose warfarin throughout pregnancy in patients with mechanical heart valve prosthesis: a meta-analysis. Interact Cardiovasc Thorac Surg 18: 797–806, 2014 1） Bousser MG, Ferro JM: Cerebral venous thrombosis: an update. Lancet Neurol 6: 162–170, 2007 9） Said JM, Ignjatovic V, Monagle PT, et al.: Altered reference ranges for protein C and protein S during early pregnancy: Implications for the diagnosis of protein C and protein S deficiency during pregnancy. Thromb Haemost 103: 984–988, 2010 4） Silvis SM, Lindgren E, Hiltunen S, et al.: Postpartum period is a risk factor for cerebral venous thrombosis. Stroke 50: 501–503, 2019 16） Schindewolf M, Lindhoff-Last E, Ludwig RJ, et al.: Heparin-induced skin lesions. Lancet 380: 1867–1879, 2012 17） Gaigl Z, Klein CE, Großmann R, et al.: Managing allergy to heparins. Dtsch Arztebl 103: A2877–A2881, 2006 |
| References_xml | – reference: 9） Said JM, Ignjatovic V, Monagle PT, et al.: Altered reference ranges for protein C and protein S during early pregnancy: Implications for the diagnosis of protein C and protein S deficiency during pregnancy. Thromb Haemost 103: 984–988, 2010 – reference: 18） Hassouna A, Allam H: Limited dose warfarin throughout pregnancy in patients with mechanical heart valve prosthesis: a meta-analysis. Interact Cardiovasc Thorac Surg 18: 797–806, 2014 – reference: 1） Bousser MG, Ferro JM: Cerebral venous thrombosis: an update. Lancet Neurol 6: 162–170, 2007 – reference: 12） Shen MC, Wu WJ, Cheng PJ, et al.: Low-molecular-weight-heparin can benefit women with recurrent pregnancy loss and sole protein S deficiency: a historical control cohort study from Taiwan. Thromb J 14: 44, 2016 – reference: 3） Cantú C, Barinagarrementeria F: Cerebral venous thrombosis associated with pregnancy and puerperium. Review of 67 cases. Stroke 24: 1880–1884, 1993 – reference: 14） Goldman AM, Mestman JH: Transient non-autoimmune hyperthyroidism of early pregnancy. J Thyroid Res 2011: 142413, 2011 – reference: 17） Gaigl Z, Klein CE, Großmann R, et al.: Managing allergy to heparins. Dtsch Arztebl 103: A2877–A2881, 2006 – reference: 20） Mazzolai L, Hohlfeld P, Spertini F, et al.: Fondaparinux is a safe alternative in case of heparin intolerance during pregnancy. Blood 108: 1569–1570, 2006 – reference: 2） Ferro JM, Canhão P, Stam J, et al.: Prognosis of cerebral vein and dural sinus thrombosis: results of the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT). Stroke 35: 664–670, 2004 – reference: 8） Comp PC, Thurnau GR, Welsh J, et al.: Functional and immunologic protein S levels are decreased during pregnancy. Blood 68: 881–885, 1986 – reference: 10） Malm J, Laurell M, Dahlbäck B: Changes in the plasma levels of vitamin K-dependent proteins C and S and of C4b-binding protein during pregnancy and oral contraception. Br J Haematol 68: 437–443, 1988 – reference: 16） Schindewolf M, Lindhoff-Last E, Ludwig RJ, et al.: Heparin-induced skin lesions. Lancet 380: 1867–1879, 2012 – reference: 6） Liang ZW, Gao WL, Feng LM: Clinical characteristics and prognosis of cerebral venous thrombosis in Chinese women during pregnancy and puerperium. Sci Rep 7: 43866, 2017 – reference: 7） Gilabert J, Fernandez JA, España F, et al.: Physiological coagulation inhibitors (protein S, protein C and antithrombin III) in severe preeclamptic states and in users of oral contraceptives. Thromb Res 49: 319–329, 1988 – reference: 15） Debeij J, van Zaane B, Dekkers OM, et al.: High levels of procoagulant factors mediate the association between free thyroxine and the risk of venous thrombosis: the MEGA study. J Thromb Haemost 12: 839–846, 2014 – reference: 4） Silvis SM, Lindgren E, Hiltunen S, et al.: Postpartum period is a risk factor for cerebral venous thrombosis. Stroke 50: 501–503, 2019 – reference: 13） Albaar MT, Adam JM: Gestational transient thyrotoxicosis. Acta Med Indones 41: 99–104, 2009 – reference: 19） Weberschock T, Meister AC, Bohrt K, et al.: The risk for cross-reactions after a cutaneous delayed-type hypersensitivity reaction to heparin preparations is independent of their molecular weight: a systematic review. Contact Dermatitis 65: 187–194, 2011 – reference: 11） Alfirevic Z, Roberts D, Martlew V: How strong is the association between maternal thrombophilia and adverse pregnancy outcome? A systematic review. Eur J Obstet Gynecol Reprod Biol 101: 6–14, 2002 – reference: 5） 赤澤宗俊，東條伸平，権丈洋徳ら：妊娠に伴う脳静脈洞血栓症について：自験例を含む本邦73例の文献的検討．日周産期・新生児会誌 48: 87–94, 2012 |
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| Snippet | ... 要旨:症例は30歳女性. 妊娠6週の悪阻出現後, 7週に頭痛, 8週に右片麻痺を認めた. 意識はJCS-1で, 右半側空間無視と右片麻痺を認めた. 頭部MRI/MRVにて脳静脈洞血栓症と診断した. 血液検査から, プロテインS欠乏症と妊娠時一過性甲状腺機能亢進症が原因と考えられた.... |
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| StartPage | 56 |
| SubjectTerms | cerebral venous sinus thrombosis early pregnancy heparin-induced allergy protein S deficiency transient hyperthyroidism during pregnancy |
| Title | 妊娠初期にプロテインS欠乏症と妊娠時一過性甲状腺機能亢進症を契機に発症した脳静脈洞血栓症の治療中にヘパリンアレルギーを来した1例 |
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