血栓性血小板减少性紫癜发病机制及诊疗进展
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摘要
<正>血栓性血小板减少性紫瘢(thrombotic thrombocytopenic purpura,TTP)临床较少见,发病率约为3.7/100万,发病年龄多为10～40岁,女性较多见,男女比例约1∶2。该病起病急骤,未及时治疗致死率可达90%~([1])。TTP发病机制主要由于ADAMTS13基因突变或产生抗ADAMTS13自身抗体导致ADAMTS13活性降低,体内形成的超大分子量vWF无法被裂解,并通过介导血小板粘附、聚
Thrombotic thrombocytopenic purpura(TTP)is a disease characterized by thrombocytopenia and microvascular thrombosis.The disease is acute,the condition is dangerous,and the early death rate can reach 90%.This article intends to review the pathogenesis,diagnosis and treatment progress of TTP in order to improve the understanding and treatment of TTP among clinicians and improve the prognosis of patients with TTP.
Thrombotic thrombocytopenic purpura(TTP)is a disease characterized by thrombocytopenia and microvascular thrombosis.The disease is acute,the condition is dangerous,and the early death rate can reach 90%.This article intends to review the pathogenesis,diagnosis and treatment progress of TTP in order to improve the understanding and treatment of TTP among clinicians and improve the prognosis of patients with TTP.
引文
[1]阮长耿,余自强.2012版血栓性血小板减少性紫癜诊断与治疗中国专家共识解读[J].临床血液学杂志,2013,26(3):145-146.
[2]Sadler JE.What's new in the diagnosis and pathophysiology of thrombotic thrombocytopenic purpura[J].Hematology,2015,2015:631-636.
[3]Joly BS,Coppo P,Veyradier A.Thrombotic thrombocytopenic purpura[J].Blood,2017,129:2836-2846.
[4]田利伟,李小丰,金鑫,等.血栓性血小板减少性紫癜患者3例分析[J].中国实验诊断学,2016,20(7):1183-1185.
[5]Crawley JT,de Groot R,Xiang Y,et al.Unravelling the scussile bond:how ADAMTS13recognizes and cleaves von Willebrand factor[J].Blood,2011,118:3212-3221.
[6]Banno F,Kokame K,Okuda T,et al.Complete deficiency in ADAMTS13is prothrombotic,but it alone is not sufficient to cause thrombotic thrombocytopenic purpura[J].Blood,2006,107:3161-3166.
[7]张军,顾健.血栓性血小板减少性紫癜发病机制及治疗进展[J].临床血液学杂志,2016,29(1):73-76.
[8]Levy GG,Nichols WC,Lian EC,et al.Mutations in a member of the ADAMTS gene family cause thrombotic thrombocytopenic purpura[J].Nature,2001,413:488-494.
[9]Lotta LA,Garagiola I,Palla R,et al.ADAMTS13mutations and polymorphisms in congenital thrombotic thrombocytopenic purpura[J].Hum Mutat,2010,31:11-19.
[10]Schiviz A,Wuersch K,Piskernik C,et al.A new mouse model mimicking thrombotic thrombocytopenic purpura:correction of symptoms by recombinant human ADAMTS13[J].Blood,2012,119:6128-6135.
[11]George JN,Lopez JA,Konkle BA.N-Acetylcysteine:an old drug,a new insight,apotentially effective treatment for thrombotic thrombocytopenic purpura[J].Transfusion,2014,54:1205-1207.
[12]Sayani FA,Abrams CS.How I treat refractory thrombotic thrombocytopenic purpura[J].Blood,2015,125:3860-3867.
[13]Chen J,Reheman A,Gushiken FC,et al.N-acetylcysteine reduces the size and activity of von Willebrand factor in human plasma and mice[J].J Clin Invest,2011,121:593-603.
[14]Rottenstreich A,Hochberg-Klein S,Rund D,et al.The role of N-acetylcysteine in the treatment of thrombotic thrombocytopenic purpura[J].J Thromb Thrombolysis,2016,41:678-683.
[15]Shortt J,Oh DH,Opat SS.ADAMTS13antibody depletion by bortezomib in thrombotic thrombocytopenic purpura[J].N Engl J Med,2013,368:90-92.
[16]Mazepa MA,Raval JS,Moll S,et al.Bortezomib induces clinical remission and reduction of ADAMTS13inhibitory antibodies in relapsed refractory idiopathic thrombotic thrombocytopenic purpura[J].Br JHaematol,2014,164:900-902.
[17]Patriquin CJ,Thomas MR,Dutt T,et al.Bortezomib in the treatment of refractory thrombotic thrombocytopenic purpura[J].Br J Haematol,2016,173:779-785.
[18]Eskazan AE.Bortezomib therapy in patients with relapsed/refractory acquired thrombotic thrombocytopenic purpura[J].Ann Hematol,2016,95:1751-1756.
[19]Crawley JT,Scully MA.Thrombotic thrombocytopenic purpura:basic pathophysiology and therapeutic strategies[J].Hematology(Am Soc Hematol Educ Program),2013,2013:292-299.
[20]Knobl P,Jilma B,Gilbert JC,et al.Anti-von Willebrand factor aptamer ARC1779for refractory thrombotic thrombocytopenic purpura[J].Transfusion,2009,49:2181-2185.
[21]Callewaert F,Roodt J,Ulrichts H,et al.Evaluation of efficacy and safety of the anti-VWF Nanobody ALX-0681in a preclinical baboon model of acquired thrombotic thrombocytopenic purpura[J].Blood,2012,120:3603-3610.
[22]Feys HB,Roodt J,Vandeputte N,et al.Inhibition of von Willebrand factor-platelet glycoprotein Ib interaction prevents and reverses symptoms of acute acquired thrombotic thrombocytopenic purpura in baboons[J].Blood,2012,120:3611-3614.
[23]Peyvandi F,Scully M,Kremer Hovinga JA,et al.Caplacizumab for acquired thrombotic thrombocytopenic purpura[J].N Engl J Med,2016,374:511-522.
[24]Scully M,Cataland SR.Results of the randomized,double-blind,placebo-controlled,phase 3 hercules study of caplacizumab in patients with acquired thrombotic thrombocytopenic purpura[J].Blood,2017,130(Suppl 1):LBA-1.
[25]Scully M,Hunt BJ,Benjamin S,et al.Guidelines on the diagnosis and management of thrombotic thrombocytopenic purpura and other thrombotic microangiopathies[J].Br J Haematol,2012,158:323-325.
[26]Kremer Hovinga JA,Vesely SK,Terrell DR,et al.Survival and relapse in patients with thrombotic thrombocytopenic purpura[J].Blood,2010,115:1500-1511.
[27]Bresin E,Gastoldi S,Daina E,et al.Rituximab as preemptive treatment in patient with thrpmbotic thrombocytopenic purpura and evidence of anti-ADAMTS13autoantibodies[J].Thromb Haemost,2009,101:233-238.
[28]Hie M,Gay J,Galicier L,et al.Preemptive rituximab infusions after remission efficiently prevent relapses in acquired thrombotic thrombocytopenic purpura[J].Blood,2014,124:204-210.
[29]吕翠翠,孙甜甜,鞠满凯,等.57例血栓性血小板减少性紫癜患者的临床分析[J].临床血液学杂志,2015,28(11):957-965.
[2]Sadler JE.What's new in the diagnosis and pathophysiology of thrombotic thrombocytopenic purpura[J].Hematology,2015,2015:631-636.
[3]Joly BS,Coppo P,Veyradier A.Thrombotic thrombocytopenic purpura[J].Blood,2017,129:2836-2846.
[4]田利伟,李小丰,金鑫,等.血栓性血小板减少性紫癜患者3例分析[J].中国实验诊断学,2016,20(7):1183-1185.
[5]Crawley JT,de Groot R,Xiang Y,et al.Unravelling the scussile bond:how ADAMTS13recognizes and cleaves von Willebrand factor[J].Blood,2011,118:3212-3221.
[6]Banno F,Kokame K,Okuda T,et al.Complete deficiency in ADAMTS13is prothrombotic,but it alone is not sufficient to cause thrombotic thrombocytopenic purpura[J].Blood,2006,107:3161-3166.
[7]张军,顾健.血栓性血小板减少性紫癜发病机制及治疗进展[J].临床血液学杂志,2016,29(1):73-76.
[8]Levy GG,Nichols WC,Lian EC,et al.Mutations in a member of the ADAMTS gene family cause thrombotic thrombocytopenic purpura[J].Nature,2001,413:488-494.
[9]Lotta LA,Garagiola I,Palla R,et al.ADAMTS13mutations and polymorphisms in congenital thrombotic thrombocytopenic purpura[J].Hum Mutat,2010,31:11-19.
[10]Schiviz A,Wuersch K,Piskernik C,et al.A new mouse model mimicking thrombotic thrombocytopenic purpura:correction of symptoms by recombinant human ADAMTS13[J].Blood,2012,119:6128-6135.
[11]George JN,Lopez JA,Konkle BA.N-Acetylcysteine:an old drug,a new insight,apotentially effective treatment for thrombotic thrombocytopenic purpura[J].Transfusion,2014,54:1205-1207.
[12]Sayani FA,Abrams CS.How I treat refractory thrombotic thrombocytopenic purpura[J].Blood,2015,125:3860-3867.
[13]Chen J,Reheman A,Gushiken FC,et al.N-acetylcysteine reduces the size and activity of von Willebrand factor in human plasma and mice[J].J Clin Invest,2011,121:593-603.
[14]Rottenstreich A,Hochberg-Klein S,Rund D,et al.The role of N-acetylcysteine in the treatment of thrombotic thrombocytopenic purpura[J].J Thromb Thrombolysis,2016,41:678-683.
[15]Shortt J,Oh DH,Opat SS.ADAMTS13antibody depletion by bortezomib in thrombotic thrombocytopenic purpura[J].N Engl J Med,2013,368:90-92.
[16]Mazepa MA,Raval JS,Moll S,et al.Bortezomib induces clinical remission and reduction of ADAMTS13inhibitory antibodies in relapsed refractory idiopathic thrombotic thrombocytopenic purpura[J].Br JHaematol,2014,164:900-902.
[17]Patriquin CJ,Thomas MR,Dutt T,et al.Bortezomib in the treatment of refractory thrombotic thrombocytopenic purpura[J].Br J Haematol,2016,173:779-785.
[18]Eskazan AE.Bortezomib therapy in patients with relapsed/refractory acquired thrombotic thrombocytopenic purpura[J].Ann Hematol,2016,95:1751-1756.
[19]Crawley JT,Scully MA.Thrombotic thrombocytopenic purpura:basic pathophysiology and therapeutic strategies[J].Hematology(Am Soc Hematol Educ Program),2013,2013:292-299.
[20]Knobl P,Jilma B,Gilbert JC,et al.Anti-von Willebrand factor aptamer ARC1779for refractory thrombotic thrombocytopenic purpura[J].Transfusion,2009,49:2181-2185.
[21]Callewaert F,Roodt J,Ulrichts H,et al.Evaluation of efficacy and safety of the anti-VWF Nanobody ALX-0681in a preclinical baboon model of acquired thrombotic thrombocytopenic purpura[J].Blood,2012,120:3603-3610.
[22]Feys HB,Roodt J,Vandeputte N,et al.Inhibition of von Willebrand factor-platelet glycoprotein Ib interaction prevents and reverses symptoms of acute acquired thrombotic thrombocytopenic purpura in baboons[J].Blood,2012,120:3611-3614.
[23]Peyvandi F,Scully M,Kremer Hovinga JA,et al.Caplacizumab for acquired thrombotic thrombocytopenic purpura[J].N Engl J Med,2016,374:511-522.
[24]Scully M,Cataland SR.Results of the randomized,double-blind,placebo-controlled,phase 3 hercules study of caplacizumab in patients with acquired thrombotic thrombocytopenic purpura[J].Blood,2017,130(Suppl 1):LBA-1.
[25]Scully M,Hunt BJ,Benjamin S,et al.Guidelines on the diagnosis and management of thrombotic thrombocytopenic purpura and other thrombotic microangiopathies[J].Br J Haematol,2012,158:323-325.
[26]Kremer Hovinga JA,Vesely SK,Terrell DR,et al.Survival and relapse in patients with thrombotic thrombocytopenic purpura[J].Blood,2010,115:1500-1511.
[27]Bresin E,Gastoldi S,Daina E,et al.Rituximab as preemptive treatment in patient with thrpmbotic thrombocytopenic purpura and evidence of anti-ADAMTS13autoantibodies[J].Thromb Haemost,2009,101:233-238.
[28]Hie M,Gay J,Galicier L,et al.Preemptive rituximab infusions after remission efficiently prevent relapses in acquired thrombotic thrombocytopenic purpura[J].Blood,2014,124:204-210.
[29]吕翠翠,孙甜甜,鞠满凯,等.57例血栓性血小板减少性紫癜患者的临床分析[J].临床血液学杂志,2015,28(11):957-965.