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Platelet activation with unfractionated heparin at therapeutic concentrations and comparisons with a low-molecular-weight heparin and with a direct thrombin inhibitor
The growing use of heparin in acute thrombotic disorders, coupled with the availability of many new antithrombotic agents, emphasizes the need for adequate characterization of the platelet effects of the various anticoagulants. Controversial platelet effects have been reported with heparin (eg, enha...
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| Published in: | Circulation (New York, N.Y.) N.Y.), 1998-01, Vol.97 (3), p.251-256 |
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| cites | cdi_FETCH-LOGICAL-c475t-41dbb6fada61efc7d4267cacaa8e5915aa27633ba9a733dc0adc5707927c79ff3 |
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| container_title | Circulation (New York, N.Y.) |
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| creator | XIAO, Z THEROUX, P |
| description | The growing use of heparin in acute thrombotic disorders, coupled with the availability of many new antithrombotic agents, emphasizes the need for adequate characterization of the platelet effects of the various anticoagulants. Controversial platelet effects have been reported with heparin (eg, enhanced platelet activation in vitro with high doses and no such effect in vivo at therapeutic doses). This study examined platelet receptor activation and platelet aggregation at therapeutic concentrations of unfractionated heparin (UFH), of enoxaparin, a low-molecular-weight heparin, and of argatroban, a direct thrombin inhibitor.
Platelet P-selectin (CD62) and activated GP IIb/IIIa (PAC-1) expression on platelet membrane was quantified in whole blood as well as platelet aggregation in platelet-rich plasma in 43 patients with unstable angina before and during treatment with UFH or enoxaparin. Studies were also carried out in blood of seven normal volunteers after addition ex vivo of UFH (0.25 U/mL), enoxaparin (0.25 U/mL), argatroban (1 ng/mL), and normal saline. UFH in patients with unstable angina increased the percentage of circulating platelets positive to PAC-1 from 2.7+/-1.7% to 4.4+/-3.4% (P |
| doi_str_mv | 10.1161/01.CIR.97.3.251 |
| format | article |
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Platelet P-selectin (CD62) and activated GP IIb/IIIa (PAC-1) expression on platelet membrane was quantified in whole blood as well as platelet aggregation in platelet-rich plasma in 43 patients with unstable angina before and during treatment with UFH or enoxaparin. Studies were also carried out in blood of seven normal volunteers after addition ex vivo of UFH (0.25 U/mL), enoxaparin (0.25 U/mL), argatroban (1 ng/mL), and normal saline. UFH in patients with unstable angina increased the percentage of circulating platelets positive to PAC-1 from 2.7+/-1.7% to 4.4+/-3.4% (P<.05) and to CD62 from 1.6+/-0.9% to 2.7+/-1.5% (P<.01). Platelets were also hyperresponsive to stimulation with ADP and with the thrombin-receptor agonist peptide. Aggregation to ADP increased from 6.8+/-4.6% to 11.2+/-7.0% and to TRAP from 5.2+/-3.5% to 11.1+/-6.0% (P<.001). The addition of UFH to blood of normal volunteers resulted also in activation of GP IIb/IIIa receptors, expression of P-selectin, and enhanced platelet aggregation. Enoxaparin had only minor effects on platelet activation in vivo and ex vivo, and argatroban, evaluated ex vivo, had no detectable effects.
Therapeutic concentrations of UFH are associated with platelet activation.</description><identifier>ISSN: 0009-7322</identifier><identifier>EISSN: 1524-4539</identifier><identifier>DOI: 10.1161/01.CIR.97.3.251</identifier><identifier>PMID: 9462526</identifier><identifier>CODEN: CIRCAZ</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>Adenosine Diphosphate - pharmacology ; Adult ; Aged ; Aged, 80 and over ; Angina, Unstable - blood ; Angina, Unstable - drug therapy ; Anticoagulants - administration & dosage ; Anticoagulants - therapeutic use ; Antithrombins - administration & dosage ; Antithrombins - therapeutic use ; Biological and medical sciences ; Blood. Blood coagulation. Reticuloendothelial system ; Dose-Response Relationship, Drug ; Enoxaparin - administration & dosage ; Enoxaparin - therapeutic use ; Female ; Heparin - administration & dosage ; Heparin - therapeutic use ; Humans ; Male ; Medical sciences ; Middle Aged ; P-Selectin - blood ; P-Selectin - drug effects ; Partial Thromboplastin Time ; Peptide Fragments - pharmacology ; Pharmacology. Drug treatments ; Pipecolic Acids - administration & dosage ; Pipecolic Acids - therapeutic use ; Platelet Activation - drug effects ; Platelet Count ; Platelet Glycoprotein GPIIb-IIIa Complex - drug effects ; Platelet Glycoprotein GPIIb-IIIa Complex - metabolism</subject><ispartof>Circulation (New York, N.Y.), 1998-01, Vol.97 (3), p.251-256</ispartof><rights>1998 INIST-CNRS</rights><rights>Copyright American Heart Association, Inc. Jan 27, 1998</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c475t-41dbb6fada61efc7d4267cacaa8e5915aa27633ba9a733dc0adc5707927c79ff3</citedby><cites>FETCH-LOGICAL-c475t-41dbb6fada61efc7d4267cacaa8e5915aa27633ba9a733dc0adc5707927c79ff3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27915,27916</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=2128574$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9462526$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>XIAO, Z</creatorcontrib><creatorcontrib>THEROUX, P</creatorcontrib><title>Platelet activation with unfractionated heparin at therapeutic concentrations and comparisons with a low-molecular-weight heparin and with a direct thrombin inhibitor</title><title>Circulation (New York, N.Y.)</title><addtitle>Circulation</addtitle><description>The growing use of heparin in acute thrombotic disorders, coupled with the availability of many new antithrombotic agents, emphasizes the need for adequate characterization of the platelet effects of the various anticoagulants. Controversial platelet effects have been reported with heparin (eg, enhanced platelet activation in vitro with high doses and no such effect in vivo at therapeutic doses). This study examined platelet receptor activation and platelet aggregation at therapeutic concentrations of unfractionated heparin (UFH), of enoxaparin, a low-molecular-weight heparin, and of argatroban, a direct thrombin inhibitor.
Platelet P-selectin (CD62) and activated GP IIb/IIIa (PAC-1) expression on platelet membrane was quantified in whole blood as well as platelet aggregation in platelet-rich plasma in 43 patients with unstable angina before and during treatment with UFH or enoxaparin. Studies were also carried out in blood of seven normal volunteers after addition ex vivo of UFH (0.25 U/mL), enoxaparin (0.25 U/mL), argatroban (1 ng/mL), and normal saline. UFH in patients with unstable angina increased the percentage of circulating platelets positive to PAC-1 from 2.7+/-1.7% to 4.4+/-3.4% (P<.05) and to CD62 from 1.6+/-0.9% to 2.7+/-1.5% (P<.01). Platelets were also hyperresponsive to stimulation with ADP and with the thrombin-receptor agonist peptide. Aggregation to ADP increased from 6.8+/-4.6% to 11.2+/-7.0% and to TRAP from 5.2+/-3.5% to 11.1+/-6.0% (P<.001). The addition of UFH to blood of normal volunteers resulted also in activation of GP IIb/IIIa receptors, expression of P-selectin, and enhanced platelet aggregation. Enoxaparin had only minor effects on platelet activation in vivo and ex vivo, and argatroban, evaluated ex vivo, had no detectable effects.
Therapeutic concentrations of UFH are associated with platelet activation.</description><subject>Adenosine Diphosphate - pharmacology</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Angina, Unstable - blood</subject><subject>Angina, Unstable - drug therapy</subject><subject>Anticoagulants - administration & dosage</subject><subject>Anticoagulants - therapeutic use</subject><subject>Antithrombins - administration & dosage</subject><subject>Antithrombins - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Blood. Blood coagulation. Reticuloendothelial system</subject><subject>Dose-Response Relationship, Drug</subject><subject>Enoxaparin - administration & dosage</subject><subject>Enoxaparin - therapeutic use</subject><subject>Female</subject><subject>Heparin - administration & dosage</subject><subject>Heparin - therapeutic use</subject><subject>Humans</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>P-Selectin - blood</subject><subject>P-Selectin - drug effects</subject><subject>Partial Thromboplastin Time</subject><subject>Peptide Fragments - pharmacology</subject><subject>Pharmacology. Drug treatments</subject><subject>Pipecolic Acids - administration & dosage</subject><subject>Pipecolic Acids - therapeutic use</subject><subject>Platelet Activation - drug effects</subject><subject>Platelet Count</subject><subject>Platelet Glycoprotein GPIIb-IIIa Complex - drug effects</subject><subject>Platelet Glycoprotein GPIIb-IIIa Complex - metabolism</subject><issn>0009-7322</issn><issn>1524-4539</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><recordid>eNpdkU-L1TAUxYM4jM_RtSshiLhrp0ma5GUpD_8MDMwgug63aWoztMkzSX34hfyck86UEVyFe8_vnBs4CL0hTU2IIJcNqQ9X32ola1ZTTp6hHeG0rVrO1HO0a5pGVZJR-gK9TOmujIJJfo7OVSsop2KH_t5OkO1kMwaT3W_ILnh8cnnEix_iugu-AD0e7RGi8xgyzqONcLRLdgab4I31OT4YEwbfl9W8ommdH5IAT-FUzWGyZpkgVifrfo75X2LxbFzvojXrgRjmrkjOj65zOcRX6GyAKdnX23uBfnz-9P3wtbq--XJ1-HhdmVbyXLWk7zoxQA-C2MHIvqVCGjAAe8sV4QBUCsY6UCAZ600DveGykYpKI9UwsAv04TH3GMOvxaasZ5eMnSbwNixJSyXkfk9ZAd_9B96FJfryN00JFZxzJgt0-QiZGFKKdtDH6GaIfzRp9Fqfbogu9WklNdOlvuJ4u8Uu3Wz7J37rq-jvNx2Sgak05I1LT1g5veeyZfcbPqfD</recordid><startdate>19980127</startdate><enddate>19980127</enddate><creator>XIAO, Z</creator><creator>THEROUX, P</creator><general>Lippincott Williams & Wilkins</general><general>American Heart Association, Inc</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>K9.</scope><scope>NAPCQ</scope><scope>U9A</scope><scope>7X8</scope></search><sort><creationdate>19980127</creationdate><title>Platelet activation with unfractionated heparin at therapeutic concentrations and comparisons with a low-molecular-weight heparin and with a direct thrombin inhibitor</title><author>XIAO, Z ; THEROUX, P</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c475t-41dbb6fada61efc7d4267cacaa8e5915aa27633ba9a733dc0adc5707927c79ff3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1998</creationdate><topic>Adenosine Diphosphate - pharmacology</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Angina, Unstable - blood</topic><topic>Angina, Unstable - drug therapy</topic><topic>Anticoagulants - administration & dosage</topic><topic>Anticoagulants - therapeutic use</topic><topic>Antithrombins - administration & dosage</topic><topic>Antithrombins - therapeutic use</topic><topic>Biological and medical sciences</topic><topic>Blood. Blood coagulation. Reticuloendothelial system</topic><topic>Dose-Response Relationship, Drug</topic><topic>Enoxaparin - administration & dosage</topic><topic>Enoxaparin - therapeutic use</topic><topic>Female</topic><topic>Heparin - administration & dosage</topic><topic>Heparin - therapeutic use</topic><topic>Humans</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>P-Selectin - blood</topic><topic>P-Selectin - drug effects</topic><topic>Partial Thromboplastin Time</topic><topic>Peptide Fragments - pharmacology</topic><topic>Pharmacology. Drug treatments</topic><topic>Pipecolic Acids - administration & dosage</topic><topic>Pipecolic Acids - therapeutic use</topic><topic>Platelet Activation - drug effects</topic><topic>Platelet Count</topic><topic>Platelet Glycoprotein GPIIb-IIIa Complex - drug effects</topic><topic>Platelet Glycoprotein GPIIb-IIIa Complex - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>XIAO, Z</creatorcontrib><creatorcontrib>THEROUX, P</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>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>Circulation (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>XIAO, Z</au><au>THEROUX, P</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Platelet activation with unfractionated heparin at therapeutic concentrations and comparisons with a low-molecular-weight heparin and with a direct thrombin inhibitor</atitle><jtitle>Circulation (New York, N.Y.)</jtitle><addtitle>Circulation</addtitle><date>1998-01-27</date><risdate>1998</risdate><volume>97</volume><issue>3</issue><spage>251</spage><epage>256</epage><pages>251-256</pages><issn>0009-7322</issn><eissn>1524-4539</eissn><coden>CIRCAZ</coden><abstract>The growing use of heparin in acute thrombotic disorders, coupled with the availability of many new antithrombotic agents, emphasizes the need for adequate characterization of the platelet effects of the various anticoagulants. Controversial platelet effects have been reported with heparin (eg, enhanced platelet activation in vitro with high doses and no such effect in vivo at therapeutic doses). This study examined platelet receptor activation and platelet aggregation at therapeutic concentrations of unfractionated heparin (UFH), of enoxaparin, a low-molecular-weight heparin, and of argatroban, a direct thrombin inhibitor.
Platelet P-selectin (CD62) and activated GP IIb/IIIa (PAC-1) expression on platelet membrane was quantified in whole blood as well as platelet aggregation in platelet-rich plasma in 43 patients with unstable angina before and during treatment with UFH or enoxaparin. Studies were also carried out in blood of seven normal volunteers after addition ex vivo of UFH (0.25 U/mL), enoxaparin (0.25 U/mL), argatroban (1 ng/mL), and normal saline. UFH in patients with unstable angina increased the percentage of circulating platelets positive to PAC-1 from 2.7+/-1.7% to 4.4+/-3.4% (P<.05) and to CD62 from 1.6+/-0.9% to 2.7+/-1.5% (P<.01). Platelets were also hyperresponsive to stimulation with ADP and with the thrombin-receptor agonist peptide. Aggregation to ADP increased from 6.8+/-4.6% to 11.2+/-7.0% and to TRAP from 5.2+/-3.5% to 11.1+/-6.0% (P<.001). The addition of UFH to blood of normal volunteers resulted also in activation of GP IIb/IIIa receptors, expression of P-selectin, and enhanced platelet aggregation. Enoxaparin had only minor effects on platelet activation in vivo and ex vivo, and argatroban, evaluated ex vivo, had no detectable effects.
Therapeutic concentrations of UFH are associated with platelet activation.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>9462526</pmid><doi>10.1161/01.CIR.97.3.251</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Circulation (New York, N.Y.), 1998-01, Vol.97 (3), p.251-256 |
| issn | 0009-7322 1524-4539 |
| language | eng |
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| source | EZB Electronic Journals Library |
| subjects | Adenosine Diphosphate - pharmacology Adult Aged Aged, 80 and over Angina, Unstable - blood Angina, Unstable - drug therapy Anticoagulants - administration & dosage Anticoagulants - therapeutic use Antithrombins - administration & dosage Antithrombins - therapeutic use Biological and medical sciences Blood. Blood coagulation. Reticuloendothelial system Dose-Response Relationship, Drug Enoxaparin - administration & dosage Enoxaparin - therapeutic use Female Heparin - administration & dosage Heparin - therapeutic use Humans Male Medical sciences Middle Aged P-Selectin - blood P-Selectin - drug effects Partial Thromboplastin Time Peptide Fragments - pharmacology Pharmacology. Drug treatments Pipecolic Acids - administration & dosage Pipecolic Acids - therapeutic use Platelet Activation - drug effects Platelet Count Platelet Glycoprotein GPIIb-IIIa Complex - drug effects Platelet Glycoprotein GPIIb-IIIa Complex - metabolism |
| title | Platelet activation with unfractionated heparin at therapeutic concentrations and comparisons with a low-molecular-weight heparin and with a direct thrombin inhibitor |
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