Trousseau综合征的研究进展
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摘要
在恶性肿瘤患者中存在2%～5%动脉血栓形成。Trousseau综合征包括恶性肿瘤患者因凝血和纤溶机制异常而在其发病过程中出现的所有临床表现。目前认为Trousseau综合征所致缺血性脑卒中的主要发病机制是恶性肿瘤存在使凝血系统与纤溶系统之间失衡所致的高凝状态。其主要临床特点包括D-二聚体、肿瘤标志物水平明显升高,以及累及多血管分布区的MR多发弥散加权成像(DWI)高信号表现。主要治疗手段是抗肿瘤治疗及抗凝治疗,溶栓治疗的安全性和有效性仍存在一定争议。
There are 2% to 5% of arterial thrombosis in patients with malignant tumors. Currently,Trousseau syndrome includes all clinical manifestations of malignant tumors in the course of their onset due to abnormal blood coagulation and fibrinolysis mechanisms. It is currently believed that the main pathogenesis of ischemic stroke caused by Trousseau syndrome is a hypercoagulable state caused by the imbalance between the coagulation system and the fibrinolytic system. The main clinical features include a significant increase in D-dimer levels and marked elevation of tumor markers,and multiple diffuse weighted imaging( DWI) high-signal performance involving multiple blood vessel distribution areas. The main treatment for Trousseau syndrome is anti-tumor therapy and anticoagulant therapy. The safety and efficacy of thrombolytic therapy remains controversial.
There are 2% to 5% of arterial thrombosis in patients with malignant tumors. Currently,Trousseau syndrome includes all clinical manifestations of malignant tumors in the course of their onset due to abnormal blood coagulation and fibrinolysis mechanisms. It is currently believed that the main pathogenesis of ischemic stroke caused by Trousseau syndrome is a hypercoagulable state caused by the imbalance between the coagulation system and the fibrinolytic system. The main clinical features include a significant increase in D-dimer levels and marked elevation of tumor markers,and multiple diffuse weighted imaging( DWI) high-signal performance involving multiple blood vessel distribution areas. The main treatment for Trousseau syndrome is anti-tumor therapy and anticoagulant therapy. The safety and efficacy of thrombolytic therapy remains controversial.
引文
[1]Chew TW,Gau CS,Wen YW,et al.Epidemiology,clinical profile and treatment patterns of venous thromboembolism in cancer patients in Taiwan:a population-based study[J].BMCCancer,2015,15:298
[2]Libourel EJ,Sonneveld P,van der Holt B,et al.High incidence of arterial thrombosis in young patients treated for multiple myeloma:results of a prospective cohort study[J].Blood,2010,116:22-26
[3]Kristinsson SY,Pfeiffer RM,Bj9rkholm M,et al.Arterial and venous thrombosis in monoclonal gammopathy of undetermined significance and multiple myeloma:a population-based study[J]Blood,2010,115:4991-4998
[4]Lee KW,Bang SM,Kim S,et al.The incidence,risk factors and prognostic implications of venous thromboembolism in patients with gastric cancer[J].J Thromb Haemost,2010,8:540-547
[5]Chen PC,Muo CH,Lee YT,et al..Lung cancer and incidence of stroke:a population-based cohort study[J].Stroke,2011,42:3034-3039
[6]Kim SJ,Park JH,Lee MJ,et al.Clues to occult cancer in patients with ischemic stroke[J].PLo S One,2012,7:e44959
[7]Finelli PF,Nouh A.Three-Territory DWI Acute Infarcts:Diagnostic Value in Cancer-Associated Hypercoagulation Stroke(Trousseau Syndrome)[J].AJNR Am J Neuroradiol,2016,37:2033-2036
[8]Repetto O,De RE V.Coagulation and fibrinolysis in gastric cancer[J].Ann N Y Acad Sci,2017,1404:27-48
[9]Adess M,Eisner R,Nand S,et al.Thromboembolism in cancer patients:pathogenesis and treatment[J].Clin Appl Thromb Hemost,2006,12:254-266
[10]Taccone FS,Jeangette SM,Blecic SA.First-ever stroke as initial presentation of systemic cancer[J].J Stroke Cerebrovasc Dis,2008,17:169-174
[11]符丹丽,陈培丰.恶性肿瘤高凝状态的中西医发病机制[J].肿瘤防治研究,2018,45:179-182
[12]郑洋,孙霈,董青,等.恶性肿瘤高凝状态发病机制与诊断标准探讨[J].中国医刊,2014,49:16-20
[13]Ikushima S,Ono R,Fukuda K,et al.Trousse's syndrome:cancer-associated thrombosis[J].Jpn J Clin Oncol,2016,46:204-208
[14]Ay C,Dunkler D,Pirker R,et al.High D-dimer levels are associated with poor prognosis in cancer patients[J].Haematologica,2012,97:1158-1164
[15]Boccaccio C,Comoglio PM.Genetic link between cancer and thrombosis[J].J Clin Oncol,2009,27:4827-4833
[16]Lee A.Cancer and thromboembolic disease:pathogenic mechanisms[J].Cancer Treat Rev,2002,28:137-140
[17]寿玮龄,崔巍.恶性肿瘤出凝血异常机制[J].协和医学杂志,2012,3:482-486
[18]崔向丽,万子睿,侯珂露,等.增加肿瘤患者血栓风险的药物概述[J].中国药物警戒,2017,14:430-434
[19]Petrelli F,Cabiddu M,Borgonovo K,et al.Risk of venous and arterial thromboembolic events associated with anti-EGFRagents:a meta-analysis of randomized clinical trials[J].Ann Oncol,2012,23:1672-1679
[20]Hsieh PC,MacGillivray C,Gannon J,et al.Local controlled intramyocardial delivery of platelet-derived growth factor improves postinfarction ventricular function without pulmonary toxicity[J].Circulation,2006,114:637-644
[21]Pectasides D,Barbounis V,Athanassiou A,et al.Cerebrovascular accidents following hormonochemotherapy in cancer patients[J].Am J Clin Oncol,1992,15:168-173
[22]Seng S,Liu Z,Chiu SK,et al.Risk of venous thromboembolism in patients with cancer treated with Cisplatin:a systematic review and meta-analysis[J].J Clin Oncol,2012,30:4416-4426
[23]Wilbers J,Kappelle AC,Kessels RP,et al.Long term cerebral and vascular complications after irradiation of the neck in head and neck cancer patients:a prospective cohort study:study rationale and protocol[J].BMC Neurol,2014,14:132
[24]Hung SK,Lee MS,Chiou WY,et al.High incidence of ischemic stroke occurrence in irradiated lung cancer patients:a populationbased surgical cohort study[J].PLo S One,2014,9:e94377
[25]Sheth RA,Niekamp A,Quencer KB,et al.Thrombosis in cancer patients:etiology,incidence,and management[J].Cardiovasc Diagn Ther,2017,7:S178-S185
[26]Dipasco PJ,Misra S,Koniaris LG,et al.Thrombophilic state in cancer,part I:biology,incidence,and risk factors[J].JSurg Oncol,2011,104:316-322
[27]Khorana AA,Connolly GC.Assessing risk of venous thromboembolism in the patient with cancer[J].J Clin Oncol,2009,27:4839-4847
[28]Aarnio K,Joensuu H,Haapaniemi E,et al.Cancer in young adults with ischemic stroke[J].Stroke,2015,46:1601-1606
[29]Nilsson G,Holmberg L,Garmo H,et al.Increased incidence of stroke in women with breast cancer[J].Eur J Cancer,2005,41:423-429
[30]Sun B,Fan S,Li Z,et al.Clinical and Neuroimaging Features of Acute Ischemic Stroke in Cancer Patients[J].Eur Neurol,2016,75:292-299
[31]Taccone FS,Jeangette SM,Blecic SA.First-ever stroke as initial presentation of systemic cancer[J].J Stroke Cerebrovasc Dis,2008,17:169-174
[32]Kim K,Lee JH.Risk factors and biomarkers of ischemic stroke in cancer patients[J].J Stroke,2014,16:91-96
[33]Yigit M,Sogut O,Yigit E,et al.The relationship between anemia and recurrence of ischemic stroke in patients with Trousseau's syndrome:A retrospective cross-sectional study[J].Turk J Emerg Med,2016,16:65-68
[34]Stein PD,Beemath A,Meyers FA,et al.Incidence of venous thromboembolism in patients hospitalized with cancer[J].Am JMed,2006,119:60-68
[35]Sandhu R,Pan CX,Wun T,et al.The incidence of venous thromboembolism and its effect on survival among patients with primary bladder cancer[J].Cancer,2010,116:2596-2603
[36]Navi BB,Singer S,Merkler AE,et al.Cryptogenic subtype predicts reduced survival among cancer patients with ischemic stroke[J].Stroke,2014,45:2292-2297
[37]Chen Y,Zeng J,Xie X,et al.Clinical features of systemic cancer patients with acute cerebral infarction and its underlying pathogenesis[J].Int J Clin Exp Med,2015,8:4455-4463
[38]Kim K,Lee JH.Risk factors and biomarkers of ischemic stroke in cancer patients[J].J Stroke,2014,16:91-96
[39]Gon Y,Okazaki S,Terasaki Y,et al.Characteristics of cryptogenic stroke in cancer patients[J].Ann Clin Transl Neurol,2016,3:280-287
[40]Seok JM,Kim SG,Kim JW,et al.Coagulopathy and embolic signal in cancer patients with ischemic stroke[J].Ann Neurol,2010,68:213-219
[41]Takeshita S,Ogata T,Mera H,et al.Multiple Thrombi in the Heart in Trousseau Syndrome Caused by Pancreatic Carcinoma[J].J Stroke Cerebrovasc Dis,2018,27:e75-e77
[42]Tsanaclis AM,Robert F.Cerebral embolism in nonbacterial thrombotic endocarditis associated with carcinoma.A clinicopathological study[J].Acta Neurol Latinoam,1976,22:86-103
[43]Lee E J,Nah HW,Kwon JY,et al.Ischemic stroke in patients with cancer:is it different from usual strokes[J].Int J Stroke,2014,9:406-412
[44]Kato T,Yasuda K,Iida H,et al.Trousseau's syndrome caused by bladder cancer producing granulocyte colony-stimulating factor and parathyroid hormone-related protein:A case report[J].Oncol Lett,2016,12:4214-4218
[45]Tesselaar ME,Romijn FP,Van Der Linden IK,et al.Microparticle-associated tissue factor activity:a link between cancer and thrombosis[J].J Thromb Haemost,2007,5:520-527
[46]Jovin TG,Boosupalli V,Zivkovic SA,et al.High titers of CA-125 may be associated with recurrent ischemic strokes in patients with cancer[J].Neurology,2005,64:1944-1945
[47]Hijikata N,Sakamoto Y,Nito C,et al.Multiple Cerebral Infarctions in a Patient with Adenomyosis on Hormone Replacement Therapy:A Case Report.[J].J Stroke Cerebrovasc Dis,2016,25:e183-184
[48]Umemura T,Yamamoto J,Akiba D,et al.Bilateral cerebral embolism as a characteristic feature of patients with Trousseau syndrome[J].J Clin Neurosci,2017,42:155-159
[49]Matsumoto N,Fukuda H,Handa A,et al.Histological Examination of Trousseau Syndrome-Related Thrombus Retrieved Through Acute Endovascular Thrombectomy:Report of 2 Cases[J].J Stroke Cerebrovasc Dis,2016,25:e227-e230
[50]Vedovati MC,Germini F,Agnelli G,et al.Direct oral anticoagulants in patients with VTE and cancer a systematic review and meta-analysis[J].Chest,2015,147:475-483
[51]Lyman GH,Khorana AA,Kuderer NM,et al.Venous thromboembolism prophylaxis and treatment in patients with cancer:American Society of Clinical Oncology clinical practice guideline update[J].J Clin Oncol,2013,31:2189-2204
[52]Kim SG,Hong JM,Kim HY,et al.Ischemic stroke in cancer patients with and without conventional mechanisms:a multycenter study in Korea[J].Stroke,2010,41:798-801
[53]Masrur S,Abdullah AR,Smith EE,et al.Risk of thrombolytic therapy for acute ischemic stroke in patients with current malignancy[J].J Stroke Cerebrovasc Dis,2011,20:124-130
[54]Nam KW,Kim CK,Kim TJ,et al.Intravenous Thrombolysis in Acute Ischemic Stroke with Active Cancer[J].Biomed Res Int,2017,2017:4635829
[55]Lee MJ,Chung JW,Ahn MJ,et al.Hypercoagulability and Mortality of Patients with Stroke and Active Cancer:The OASIS-CANCER Study[J].J Stroke,2017,19:77-87
[56]孙葳,邢海英,彭清,等.以急性多发性脑梗死为首发表现的隐匿性躯体恶性肿瘤12例报告[J].中国神经精神疾病杂志,2016,42:385-389
[2]Libourel EJ,Sonneveld P,van der Holt B,et al.High incidence of arterial thrombosis in young patients treated for multiple myeloma:results of a prospective cohort study[J].Blood,2010,116:22-26
[3]Kristinsson SY,Pfeiffer RM,Bj9rkholm M,et al.Arterial and venous thrombosis in monoclonal gammopathy of undetermined significance and multiple myeloma:a population-based study[J]Blood,2010,115:4991-4998
[4]Lee KW,Bang SM,Kim S,et al.The incidence,risk factors and prognostic implications of venous thromboembolism in patients with gastric cancer[J].J Thromb Haemost,2010,8:540-547
[5]Chen PC,Muo CH,Lee YT,et al..Lung cancer and incidence of stroke:a population-based cohort study[J].Stroke,2011,42:3034-3039
[6]Kim SJ,Park JH,Lee MJ,et al.Clues to occult cancer in patients with ischemic stroke[J].PLo S One,2012,7:e44959
[7]Finelli PF,Nouh A.Three-Territory DWI Acute Infarcts:Diagnostic Value in Cancer-Associated Hypercoagulation Stroke(Trousseau Syndrome)[J].AJNR Am J Neuroradiol,2016,37:2033-2036
[8]Repetto O,De RE V.Coagulation and fibrinolysis in gastric cancer[J].Ann N Y Acad Sci,2017,1404:27-48
[9]Adess M,Eisner R,Nand S,et al.Thromboembolism in cancer patients:pathogenesis and treatment[J].Clin Appl Thromb Hemost,2006,12:254-266
[10]Taccone FS,Jeangette SM,Blecic SA.First-ever stroke as initial presentation of systemic cancer[J].J Stroke Cerebrovasc Dis,2008,17:169-174
[11]符丹丽,陈培丰.恶性肿瘤高凝状态的中西医发病机制[J].肿瘤防治研究,2018,45:179-182
[12]郑洋,孙霈,董青,等.恶性肿瘤高凝状态发病机制与诊断标准探讨[J].中国医刊,2014,49:16-20
[13]Ikushima S,Ono R,Fukuda K,et al.Trousse's syndrome:cancer-associated thrombosis[J].Jpn J Clin Oncol,2016,46:204-208
[14]Ay C,Dunkler D,Pirker R,et al.High D-dimer levels are associated with poor prognosis in cancer patients[J].Haematologica,2012,97:1158-1164
[15]Boccaccio C,Comoglio PM.Genetic link between cancer and thrombosis[J].J Clin Oncol,2009,27:4827-4833
[16]Lee A.Cancer and thromboembolic disease:pathogenic mechanisms[J].Cancer Treat Rev,2002,28:137-140
[17]寿玮龄,崔巍.恶性肿瘤出凝血异常机制[J].协和医学杂志,2012,3:482-486
[18]崔向丽,万子睿,侯珂露,等.增加肿瘤患者血栓风险的药物概述[J].中国药物警戒,2017,14:430-434
[19]Petrelli F,Cabiddu M,Borgonovo K,et al.Risk of venous and arterial thromboembolic events associated with anti-EGFRagents:a meta-analysis of randomized clinical trials[J].Ann Oncol,2012,23:1672-1679
[20]Hsieh PC,MacGillivray C,Gannon J,et al.Local controlled intramyocardial delivery of platelet-derived growth factor improves postinfarction ventricular function without pulmonary toxicity[J].Circulation,2006,114:637-644
[21]Pectasides D,Barbounis V,Athanassiou A,et al.Cerebrovascular accidents following hormonochemotherapy in cancer patients[J].Am J Clin Oncol,1992,15:168-173
[22]Seng S,Liu Z,Chiu SK,et al.Risk of venous thromboembolism in patients with cancer treated with Cisplatin:a systematic review and meta-analysis[J].J Clin Oncol,2012,30:4416-4426
[23]Wilbers J,Kappelle AC,Kessels RP,et al.Long term cerebral and vascular complications after irradiation of the neck in head and neck cancer patients:a prospective cohort study:study rationale and protocol[J].BMC Neurol,2014,14:132
[24]Hung SK,Lee MS,Chiou WY,et al.High incidence of ischemic stroke occurrence in irradiated lung cancer patients:a populationbased surgical cohort study[J].PLo S One,2014,9:e94377
[25]Sheth RA,Niekamp A,Quencer KB,et al.Thrombosis in cancer patients:etiology,incidence,and management[J].Cardiovasc Diagn Ther,2017,7:S178-S185
[26]Dipasco PJ,Misra S,Koniaris LG,et al.Thrombophilic state in cancer,part I:biology,incidence,and risk factors[J].JSurg Oncol,2011,104:316-322
[27]Khorana AA,Connolly GC.Assessing risk of venous thromboembolism in the patient with cancer[J].J Clin Oncol,2009,27:4839-4847
[28]Aarnio K,Joensuu H,Haapaniemi E,et al.Cancer in young adults with ischemic stroke[J].Stroke,2015,46:1601-1606
[29]Nilsson G,Holmberg L,Garmo H,et al.Increased incidence of stroke in women with breast cancer[J].Eur J Cancer,2005,41:423-429
[30]Sun B,Fan S,Li Z,et al.Clinical and Neuroimaging Features of Acute Ischemic Stroke in Cancer Patients[J].Eur Neurol,2016,75:292-299
[31]Taccone FS,Jeangette SM,Blecic SA.First-ever stroke as initial presentation of systemic cancer[J].J Stroke Cerebrovasc Dis,2008,17:169-174
[32]Kim K,Lee JH.Risk factors and biomarkers of ischemic stroke in cancer patients[J].J Stroke,2014,16:91-96
[33]Yigit M,Sogut O,Yigit E,et al.The relationship between anemia and recurrence of ischemic stroke in patients with Trousseau's syndrome:A retrospective cross-sectional study[J].Turk J Emerg Med,2016,16:65-68
[34]Stein PD,Beemath A,Meyers FA,et al.Incidence of venous thromboembolism in patients hospitalized with cancer[J].Am JMed,2006,119:60-68
[35]Sandhu R,Pan CX,Wun T,et al.The incidence of venous thromboembolism and its effect on survival among patients with primary bladder cancer[J].Cancer,2010,116:2596-2603
[36]Navi BB,Singer S,Merkler AE,et al.Cryptogenic subtype predicts reduced survival among cancer patients with ischemic stroke[J].Stroke,2014,45:2292-2297
[37]Chen Y,Zeng J,Xie X,et al.Clinical features of systemic cancer patients with acute cerebral infarction and its underlying pathogenesis[J].Int J Clin Exp Med,2015,8:4455-4463
[38]Kim K,Lee JH.Risk factors and biomarkers of ischemic stroke in cancer patients[J].J Stroke,2014,16:91-96
[39]Gon Y,Okazaki S,Terasaki Y,et al.Characteristics of cryptogenic stroke in cancer patients[J].Ann Clin Transl Neurol,2016,3:280-287
[40]Seok JM,Kim SG,Kim JW,et al.Coagulopathy and embolic signal in cancer patients with ischemic stroke[J].Ann Neurol,2010,68:213-219
[41]Takeshita S,Ogata T,Mera H,et al.Multiple Thrombi in the Heart in Trousseau Syndrome Caused by Pancreatic Carcinoma[J].J Stroke Cerebrovasc Dis,2018,27:e75-e77
[42]Tsanaclis AM,Robert F.Cerebral embolism in nonbacterial thrombotic endocarditis associated with carcinoma.A clinicopathological study[J].Acta Neurol Latinoam,1976,22:86-103
[43]Lee E J,Nah HW,Kwon JY,et al.Ischemic stroke in patients with cancer:is it different from usual strokes[J].Int J Stroke,2014,9:406-412
[44]Kato T,Yasuda K,Iida H,et al.Trousseau's syndrome caused by bladder cancer producing granulocyte colony-stimulating factor and parathyroid hormone-related protein:A case report[J].Oncol Lett,2016,12:4214-4218
[45]Tesselaar ME,Romijn FP,Van Der Linden IK,et al.Microparticle-associated tissue factor activity:a link between cancer and thrombosis[J].J Thromb Haemost,2007,5:520-527
[46]Jovin TG,Boosupalli V,Zivkovic SA,et al.High titers of CA-125 may be associated with recurrent ischemic strokes in patients with cancer[J].Neurology,2005,64:1944-1945
[47]Hijikata N,Sakamoto Y,Nito C,et al.Multiple Cerebral Infarctions in a Patient with Adenomyosis on Hormone Replacement Therapy:A Case Report.[J].J Stroke Cerebrovasc Dis,2016,25:e183-184
[48]Umemura T,Yamamoto J,Akiba D,et al.Bilateral cerebral embolism as a characteristic feature of patients with Trousseau syndrome[J].J Clin Neurosci,2017,42:155-159
[49]Matsumoto N,Fukuda H,Handa A,et al.Histological Examination of Trousseau Syndrome-Related Thrombus Retrieved Through Acute Endovascular Thrombectomy:Report of 2 Cases[J].J Stroke Cerebrovasc Dis,2016,25:e227-e230
[50]Vedovati MC,Germini F,Agnelli G,et al.Direct oral anticoagulants in patients with VTE and cancer a systematic review and meta-analysis[J].Chest,2015,147:475-483
[51]Lyman GH,Khorana AA,Kuderer NM,et al.Venous thromboembolism prophylaxis and treatment in patients with cancer:American Society of Clinical Oncology clinical practice guideline update[J].J Clin Oncol,2013,31:2189-2204
[52]Kim SG,Hong JM,Kim HY,et al.Ischemic stroke in cancer patients with and without conventional mechanisms:a multycenter study in Korea[J].Stroke,2010,41:798-801
[53]Masrur S,Abdullah AR,Smith EE,et al.Risk of thrombolytic therapy for acute ischemic stroke in patients with current malignancy[J].J Stroke Cerebrovasc Dis,2011,20:124-130
[54]Nam KW,Kim CK,Kim TJ,et al.Intravenous Thrombolysis in Acute Ischemic Stroke with Active Cancer[J].Biomed Res Int,2017,2017:4635829
[55]Lee MJ,Chung JW,Ahn MJ,et al.Hypercoagulability and Mortality of Patients with Stroke and Active Cancer:The OASIS-CANCER Study[J].J Stroke,2017,19:77-87
[56]孙葳,邢海英,彭清,等.以急性多发性脑梗死为首发表现的隐匿性躯体恶性肿瘤12例报告[J].中国神经精神疾病杂志,2016,42:385-389