Effects of All-Trans-Retinoic Acid and Arsenic Trioxide on the Hemostatic Disturbance Associated with Acute Promyelocytic Leukemia

To study the in vivo effect of all- trans-retinoic acid (ATRA) and arsenic trioxide (As 2O 3) on the expression of tissue factor (TF) and the other hemostatic disturbance, a series of parameters were measured either in bone marrow blasts or plasma from acute promyelocytic leukemia (APL) patients. Th...

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Veröffentlicht in:Thrombosis research 2001-05, Vol.102 (3), p.197-204
Hauptverfasser: Zhao, Weili, Wang, Hongli, Wang, Xuefeng, Wu, Fang, Guo, Weimin, Qu, Bin, Shen, Zhixiang, Wang, Zhenyi
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container_end_page 204
container_issue 3
container_start_page 197
container_title Thrombosis research
container_volume 102
creator Zhao, Weili
Wang, Hongli
Wang, Xuefeng
Wu, Fang
Guo, Weimin
Qu, Bin
Shen, Zhixiang
Wang, Zhenyi
description To study the in vivo effect of all- trans-retinoic acid (ATRA) and arsenic trioxide (As 2O 3) on the expression of tissue factor (TF) and the other hemostatic disturbance, a series of parameters were measured either in bone marrow blasts or plasma from acute promyelocytic leukemia (APL) patients. The plasma parameters were measured by ELISA or chromogenic studies. The TF transcription was assessed using reverse transcription–polymerase chain reaction (RT-PCR) technique. The results indicated that the blast cell procoagulant activity (PCA), TF antigen of APL cell lysate, as well as the transcription of APL TF mRNA elevated at diagnosis, were reduced after ATRA or As 2O 3 therapy. The plasma level of P-selectin, TF, thrombin–antithrombin complex (TAT), soluble fibrinmonomer complex, thrombomodulin (TM), tissue factor pathway inhibitor (TFPI), plasmin–antiplasmin complex, tissue plasminogen activator (t-PA) activity, urokinase plasminogen activator (u-PA) and its receptor (u-PAR), and D-dimer (D-D) significantly increased. Fibrinogen (Fg), antigen level of protein C (PC), plasminogen (PLG) activity, α 2-plasminogen inhibitor activity (α 2-PI), and plasminogen activator inhibitor (PAI) activity were decreased at diagnosis. The protein C activity (PC:A) and protein S (PS) remained unchanged. All the parameters were restored to normal ranges after complete remission (CR) except elevation of TF and TAT in both groups, as well as PC:A, PS, and t-PA in the ATRA group. In conclusion, there existed activation of platelets and consumption of anticoagulants as well as activation of coagulation and fibrinolytic system before treatment. Both ATRA and As 2O 3 therapy downregulated the expression of TF mRNA, decreased the PCA and TF level in APL cells, significantly inhibited coagulation activation, corrected secondary hyperfibrinolysis and the other hemostatic abnormalities, and thus greatly improved the bleeding symptom in early stage of the treatment.
doi_str_mv 10.1016/S0049-3848(01)00233-X
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The plasma parameters were measured by ELISA or chromogenic studies. The TF transcription was assessed using reverse transcription–polymerase chain reaction (RT-PCR) technique. The results indicated that the blast cell procoagulant activity (PCA), TF antigen of APL cell lysate, as well as the transcription of APL TF mRNA elevated at diagnosis, were reduced after ATRA or As 2O 3 therapy. The plasma level of P-selectin, TF, thrombin–antithrombin complex (TAT), soluble fibrinmonomer complex, thrombomodulin (TM), tissue factor pathway inhibitor (TFPI), plasmin–antiplasmin complex, tissue plasminogen activator (t-PA) activity, urokinase plasminogen activator (u-PA) and its receptor (u-PAR), and D-dimer (D-D) significantly increased. Fibrinogen (Fg), antigen level of protein C (PC), plasminogen (PLG) activity, α 2-plasminogen inhibitor activity (α 2-PI), and plasminogen activator inhibitor (PAI) activity were decreased at diagnosis. The protein C activity (PC:A) and protein S (PS) remained unchanged. All the parameters were restored to normal ranges after complete remission (CR) except elevation of TF and TAT in both groups, as well as PC:A, PS, and t-PA in the ATRA group. In conclusion, there existed activation of platelets and consumption of anticoagulants as well as activation of coagulation and fibrinolytic system before treatment. 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Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; Male ; Medical sciences ; Middle Aged ; Oxides - pharmacology ; Pharmacology. 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The plasma parameters were measured by ELISA or chromogenic studies. The TF transcription was assessed using reverse transcription–polymerase chain reaction (RT-PCR) technique. The results indicated that the blast cell procoagulant activity (PCA), TF antigen of APL cell lysate, as well as the transcription of APL TF mRNA elevated at diagnosis, were reduced after ATRA or As 2O 3 therapy. The plasma level of P-selectin, TF, thrombin–antithrombin complex (TAT), soluble fibrinmonomer complex, thrombomodulin (TM), tissue factor pathway inhibitor (TFPI), plasmin–antiplasmin complex, tissue plasminogen activator (t-PA) activity, urokinase plasminogen activator (u-PA) and its receptor (u-PAR), and D-dimer (D-D) significantly increased. Fibrinogen (Fg), antigen level of protein C (PC), plasminogen (PLG) activity, α 2-plasminogen inhibitor activity (α 2-PI), and plasminogen activator inhibitor (PAI) activity were decreased at diagnosis. The protein C activity (PC:A) and protein S (PS) remained unchanged. All the parameters were restored to normal ranges after complete remission (CR) except elevation of TF and TAT in both groups, as well as PC:A, PS, and t-PA in the ATRA group. In conclusion, there existed activation of platelets and consumption of anticoagulants as well as activation of coagulation and fibrinolytic system before treatment. 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Malignant lymphomas. Malignant reticulosis. Myelofibrosis</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Oxides - pharmacology</subject><subject>Pharmacology. Drug treatments</subject><subject>Thromboplastin - drug effects</subject><subject>Thromboplastin - metabolism</subject><subject>Tissue factor</subject><subject>Tretinoin - pharmacology</subject><issn>0049-3848</issn><issn>1879-2472</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkcFu1DAQhi1ERZfCI4B8QAgOATt2NvEJRaW0lVYCwSL1Zjn2RDUkcetxgL3y5DjdFfTGaSTPN_-MPhPyjLM3nPH12y-MSVWIRjavGH_NWClEcfWArHhTq6KUdfmQrP4ix-Qx4jfGeM1V9Ygccy7WSvJyRX6f9T3YhDT0tB2GYhvNhMVnSH4K3tLWekfN5GgbEab8sI0-_PIOaJhougZ6AWPAZFJuvfeY5tiZyQJtEYP1JoGjP326zjlzAvophnEHQ7C7hd_A_B1Gb56Qo94MCE8P9YR8_XC2Pb0oNh_PL0_bTWGFYqmoFAdZCVdJkKLvBDPrWllRV6WTrlMSgIumk6UxQhjVOdP0xlbc1GINCpQUJ-TlPvcmhtsZMOnRo4VhMBOEGXXNmpqxZgGrPWhjQIzQ65voRxN3mjO9yNd38vViVjOu7-Trqzz3_LBg7kZw_6YOtjPw4gAYtGbos2vr8V66yOSy_90eg2zjh4eo0XrIWp2P-a-0C_4_l_wBPzuiZw</recordid><startdate>20010501</startdate><enddate>20010501</enddate><creator>Zhao, Weili</creator><creator>Wang, Hongli</creator><creator>Wang, Xuefeng</creator><creator>Wu, Fang</creator><creator>Guo, Weimin</creator><creator>Qu, Bin</creator><creator>Shen, Zhixiang</creator><creator>Wang, Zhenyi</creator><general>Elsevier Ltd</general><general>Elsevier Science</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20010501</creationdate><title>Effects of All-Trans-Retinoic Acid and Arsenic Trioxide on the Hemostatic Disturbance Associated with Acute Promyelocytic Leukemia</title><author>Zhao, Weili ; Wang, Hongli ; Wang, Xuefeng ; Wu, Fang ; Guo, Weimin ; Qu, Bin ; Shen, Zhixiang ; Wang, Zhenyi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c390t-591e453d54e43fb30a679c3752d4db94ee138b42aa33a9bda8fac51a736e9e943</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Acute promyelocytic leukemia</topic><topic>Adolescent</topic><topic>Adult</topic><topic>All- trans-retinoic acid</topic><topic>Antineoplastic agents</topic><topic>Arsenic Trioxide</topic><topic>Arsenicals - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Case-Control Studies</topic><topic>Chemotherapy</topic><topic>Female</topic><topic>Hematologic and hematopoietic diseases</topic><topic>Hemorrhage - drug therapy</topic><topic>Hemorrhage - etiology</topic><topic>Hemorrhage - prevention &amp; control</topic><topic>Hemostasis - drug effects</topic><topic>Hemostatics - blood</topic><topic>Humans</topic><topic>Leukemia, Promyelocytic, Acute - complications</topic><topic>Leukemia, Promyelocytic, Acute - drug therapy</topic><topic>Leukemia, Promyelocytic, Acute - physiopathology</topic><topic>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Oxides - pharmacology</topic><topic>Pharmacology. Drug treatments</topic><topic>Thromboplastin - drug effects</topic><topic>Thromboplastin - metabolism</topic><topic>Tissue factor</topic><topic>Tretinoin - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhao, Weili</creatorcontrib><creatorcontrib>Wang, Hongli</creatorcontrib><creatorcontrib>Wang, Xuefeng</creatorcontrib><creatorcontrib>Wu, Fang</creatorcontrib><creatorcontrib>Guo, Weimin</creatorcontrib><creatorcontrib>Qu, Bin</creatorcontrib><creatorcontrib>Shen, Zhixiang</creatorcontrib><creatorcontrib>Wang, Zhenyi</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Thrombosis research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhao, Weili</au><au>Wang, Hongli</au><au>Wang, Xuefeng</au><au>Wu, Fang</au><au>Guo, Weimin</au><au>Qu, Bin</au><au>Shen, Zhixiang</au><au>Wang, Zhenyi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of All-Trans-Retinoic Acid and Arsenic Trioxide on the Hemostatic Disturbance Associated with Acute Promyelocytic Leukemia</atitle><jtitle>Thrombosis research</jtitle><addtitle>Thromb Res</addtitle><date>2001-05-01</date><risdate>2001</risdate><volume>102</volume><issue>3</issue><spage>197</spage><epage>204</epage><pages>197-204</pages><issn>0049-3848</issn><eissn>1879-2472</eissn><coden>THBRAA</coden><abstract>To study the in vivo effect of all- trans-retinoic acid (ATRA) and arsenic trioxide (As 2O 3) on the expression of tissue factor (TF) and the other hemostatic disturbance, a series of parameters were measured either in bone marrow blasts or plasma from acute promyelocytic leukemia (APL) patients. The plasma parameters were measured by ELISA or chromogenic studies. The TF transcription was assessed using reverse transcription–polymerase chain reaction (RT-PCR) technique. The results indicated that the blast cell procoagulant activity (PCA), TF antigen of APL cell lysate, as well as the transcription of APL TF mRNA elevated at diagnosis, were reduced after ATRA or As 2O 3 therapy. The plasma level of P-selectin, TF, thrombin–antithrombin complex (TAT), soluble fibrinmonomer complex, thrombomodulin (TM), tissue factor pathway inhibitor (TFPI), plasmin–antiplasmin complex, tissue plasminogen activator (t-PA) activity, urokinase plasminogen activator (u-PA) and its receptor (u-PAR), and D-dimer (D-D) significantly increased. Fibrinogen (Fg), antigen level of protein C (PC), plasminogen (PLG) activity, α 2-plasminogen inhibitor activity (α 2-PI), and plasminogen activator inhibitor (PAI) activity were decreased at diagnosis. The protein C activity (PC:A) and protein S (PS) remained unchanged. All the parameters were restored to normal ranges after complete remission (CR) except elevation of TF and TAT in both groups, as well as PC:A, PS, and t-PA in the ATRA group. In conclusion, there existed activation of platelets and consumption of anticoagulants as well as activation of coagulation and fibrinolytic system before treatment. Both ATRA and As 2O 3 therapy downregulated the expression of TF mRNA, decreased the PCA and TF level in APL cells, significantly inhibited coagulation activation, corrected secondary hyperfibrinolysis and the other hemostatic abnormalities, and thus greatly improved the bleeding symptom in early stage of the treatment.</abstract><cop>New York, NY</cop><pub>Elsevier Ltd</pub><pmid>11369412</pmid><doi>10.1016/S0049-3848(01)00233-X</doi><tpages>8</tpages></addata></record>
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subjects Acute promyelocytic leukemia
Adolescent
Adult
All- trans-retinoic acid
Antineoplastic agents
Arsenic Trioxide
Arsenicals - pharmacology
Biological and medical sciences
Case-Control Studies
Chemotherapy
Female
Hematologic and hematopoietic diseases
Hemorrhage - drug therapy
Hemorrhage - etiology
Hemorrhage - prevention & control
Hemostasis - drug effects
Hemostatics - blood
Humans
Leukemia, Promyelocytic, Acute - complications
Leukemia, Promyelocytic, Acute - drug therapy
Leukemia, Promyelocytic, Acute - physiopathology
Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis
Male
Medical sciences
Middle Aged
Oxides - pharmacology
Pharmacology. Drug treatments
Thromboplastin - drug effects
Thromboplastin - metabolism
Tissue factor
Tretinoin - pharmacology
title Effects of All-Trans-Retinoic Acid and Arsenic Trioxide on the Hemostatic Disturbance Associated with Acute Promyelocytic Leukemia
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