Heparin, Platelet Aggregation, Neutrophils, and Cardiopulmonary Bypass

Cardiopulmonary bypass (CPB) is associated with both neutrophil activation and failure of platelets to form large stable aggregates. We aimed to determine the effects of heparin and of neutrophil activation on platelet aggregation in whole blood. Fourteen patients undergoing routine aortocoronary by...

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Veröffentlicht in:Thrombosis research 2000-05, Vol.98 (4), p.249-256
Hauptverfasser: Belcher, Philip R., Muriithi, Elijah W., Milne, Elodie M., Wanikiat, Payong, Wheatley, David J., Armstrong, Roma A.
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container_end_page 256
container_issue 4
container_start_page 249
container_title Thrombosis research
container_volume 98
creator Belcher, Philip R.
Muriithi, Elijah W.
Milne, Elodie M.
Wanikiat, Payong
Wheatley, David J.
Armstrong, Roma A.
description Cardiopulmonary bypass (CPB) is associated with both neutrophil activation and failure of platelets to form large stable aggregates. We aimed to determine the effects of heparin and of neutrophil activation on platelet aggregation in whole blood. Fourteen patients undergoing routine aortocoronary bypass grafting and NSAID-free for over 7 days were studied before and after heparinisation, and at end-CPB. Whole blood, anticoagulated with rHirudin, was stirred for 3 minutes, and macroaggregation in response to collagen (0.6 μg.mL −1) or the neutrophil stimulant fMLP (10 −7M) was determined by whole blood impedance aggregometry. Microaggregation was measured by counting unaggregated single platelets (corrected for haemodilution). The blood of volunteers n=14 was studied in vitro. Patients: Before CPB, heparin effectively abolished platelet macroaggregation induced by collagen (20.5 to 1.4 Ω) or fMLP (3.9 to 0 Ω) ( p
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We aimed to determine the effects of heparin and of neutrophil activation on platelet aggregation in whole blood. Fourteen patients undergoing routine aortocoronary bypass grafting and NSAID-free for over 7 days were studied before and after heparinisation, and at end-CPB. Whole blood, anticoagulated with rHirudin, was stirred for 3 minutes, and macroaggregation in response to collagen (0.6 μg.mL −1) or the neutrophil stimulant fMLP (10 −7M) was determined by whole blood impedance aggregometry. Microaggregation was measured by counting unaggregated single platelets (corrected for haemodilution). The blood of volunteers n=14 was studied in vitro. Patients: Before CPB, heparin effectively abolished platelet macroaggregation induced by collagen (20.5 to 1.4 Ω) or fMLP (3.9 to 0 Ω) ( p&lt;0.0001). CPB had no additional effect. Heparinisation also reduced the platelet count from 127 (110–170) to 95 (64–117) p=0.023 . The inhibition of macroaggregation could not be reversed by ex vivo heparinase. Volunteers: In vitro, the same heparin concentration, as measured in vivo (4 μ.mL −1), inhibited collagen-induced macroaggregation (20.3 to 14.7 Ω), but this effect was less than that observed ex vivo and was reversed by heparinase. In vitro heparin promoted fMLP macroaggregation (2.9 to 8.6 Ω). The inhibition of macroaggregation resulted from heparinisation, per se, rather than CPB and was insensitive to heparinase. There was less inhibition by in vitro heparin, which was reversible by heparinase, indicating a direct effect of heparin in vitro. 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We aimed to determine the effects of heparin and of neutrophil activation on platelet aggregation in whole blood. Fourteen patients undergoing routine aortocoronary bypass grafting and NSAID-free for over 7 days were studied before and after heparinisation, and at end-CPB. Whole blood, anticoagulated with rHirudin, was stirred for 3 minutes, and macroaggregation in response to collagen (0.6 μg.mL −1) or the neutrophil stimulant fMLP (10 −7M) was determined by whole blood impedance aggregometry. Microaggregation was measured by counting unaggregated single platelets (corrected for haemodilution). The blood of volunteers n=14 was studied in vitro. Patients: Before CPB, heparin effectively abolished platelet macroaggregation induced by collagen (20.5 to 1.4 Ω) or fMLP (3.9 to 0 Ω) ( p&lt;0.0001). CPB had no additional effect. Heparinisation also reduced the platelet count from 127 (110–170) to 95 (64–117) p=0.023 . 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Reticuloendothelial system</subject><subject>Cardiac surgery</subject><subject>Cardiopulmonary Bypass</subject><subject>Collagen</subject><subject>Collagen - pharmacology</subject><subject>Coronary Artery Bypass</subject><subject>Female</subject><subject>fMLP</subject><subject>Heparin - pharmacology</subject><subject>Hirudin</subject><subject>Hirudins - analogs &amp; derivatives</subject><subject>Hirudins - pharmacology</subject><subject>Humans</subject><subject>Leukocytes</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>N-Formylmethionine Leucyl-Phenylalanine - pharmacology</subject><subject>Neutrophils</subject><subject>Pharmacology. Drug treatments</subject><subject>Platelet Aggregation - drug effects</subject><subject>Platelet Aggregation Inhibitors - pharmacology</subject><subject>Platelet Count - drug effects</subject><subject>Platelet Function Tests</subject><subject>Recombinant Proteins - pharmacology</subject><issn>0049-3848</issn><issn>1879-2472</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkF1LwzAUhoMobn78BKUXIgpWc9J0Sa5kDucEUUG9Dml6OiNdW5NW8N_buaHeeXXg8JzzvjyEHAA9BwqjiydKuYoTyeWJUqeUMp7EsEGGIIWKGRdskwx_kAHZCeGNUhCg0m0yACoZowKGZDrDxnhXnUWPpWmxxDYaz-ce56Z1db-9x671dfPqynAWmSqPJsbnrm66clFXxn9GV5-NCWGPbBWmDLi_nrvkZXr9PJnFdw83t5PxXWwTRdsYMRHCAGOjwnImJE1zSCxkDCQKnmXGcpliajDjamRtkQtkXHKDI56nVEKyS45Xfxtfv3cYWr1wwWJZmgrrLmgBwATnaQ-mK9D6OgSPhW68W_SFNVC9FKi_BeqlHa2U_haolwGH64AuW2D-52plrAeO1oAJ1pSFN5V14ZfjNKFM9NjlCsPexodDr4N1WFnMnUfb6rx2_zT5AhKtjC0</recordid><startdate>20000515</startdate><enddate>20000515</enddate><creator>Belcher, Philip R.</creator><creator>Muriithi, Elijah W.</creator><creator>Milne, Elodie M.</creator><creator>Wanikiat, Payong</creator><creator>Wheatley, David J.</creator><creator>Armstrong, Roma A.</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>20000515</creationdate><title>Heparin, Platelet Aggregation, Neutrophils, and Cardiopulmonary Bypass</title><author>Belcher, Philip R. ; Muriithi, Elijah W. ; Milne, Elodie M. ; Wanikiat, Payong ; Wheatley, David J. ; Armstrong, Roma A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c390t-ee377a1226fc427805d13c1b218e74bbac485e5aeb496ccfd7e2484ae64d50813</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>Anticoagulants - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Blood. Blood coagulation. Reticuloendothelial system</topic><topic>Cardiac surgery</topic><topic>Cardiopulmonary Bypass</topic><topic>Collagen</topic><topic>Collagen - pharmacology</topic><topic>Coronary Artery Bypass</topic><topic>Female</topic><topic>fMLP</topic><topic>Heparin - pharmacology</topic><topic>Hirudin</topic><topic>Hirudins - analogs &amp; derivatives</topic><topic>Hirudins - pharmacology</topic><topic>Humans</topic><topic>Leukocytes</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>N-Formylmethionine Leucyl-Phenylalanine - pharmacology</topic><topic>Neutrophils</topic><topic>Pharmacology. Drug treatments</topic><topic>Platelet Aggregation - drug effects</topic><topic>Platelet Aggregation Inhibitors - pharmacology</topic><topic>Platelet Count - drug effects</topic><topic>Platelet Function Tests</topic><topic>Recombinant Proteins - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Belcher, Philip R.</creatorcontrib><creatorcontrib>Muriithi, Elijah W.</creatorcontrib><creatorcontrib>Milne, Elodie M.</creatorcontrib><creatorcontrib>Wanikiat, Payong</creatorcontrib><creatorcontrib>Wheatley, David J.</creatorcontrib><creatorcontrib>Armstrong, Roma A.</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>Belcher, Philip R.</au><au>Muriithi, Elijah W.</au><au>Milne, Elodie M.</au><au>Wanikiat, Payong</au><au>Wheatley, David J.</au><au>Armstrong, Roma A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Heparin, Platelet Aggregation, Neutrophils, and Cardiopulmonary Bypass</atitle><jtitle>Thrombosis research</jtitle><addtitle>Thromb Res</addtitle><date>2000-05-15</date><risdate>2000</risdate><volume>98</volume><issue>4</issue><spage>249</spage><epage>256</epage><pages>249-256</pages><issn>0049-3848</issn><eissn>1879-2472</eissn><coden>THBRAA</coden><abstract>Cardiopulmonary bypass (CPB) is associated with both neutrophil activation and failure of platelets to form large stable aggregates. We aimed to determine the effects of heparin and of neutrophil activation on platelet aggregation in whole blood. Fourteen patients undergoing routine aortocoronary bypass grafting and NSAID-free for over 7 days were studied before and after heparinisation, and at end-CPB. Whole blood, anticoagulated with rHirudin, was stirred for 3 minutes, and macroaggregation in response to collagen (0.6 μg.mL −1) or the neutrophil stimulant fMLP (10 −7M) was determined by whole blood impedance aggregometry. Microaggregation was measured by counting unaggregated single platelets (corrected for haemodilution). The blood of volunteers n=14 was studied in vitro. Patients: Before CPB, heparin effectively abolished platelet macroaggregation induced by collagen (20.5 to 1.4 Ω) or fMLP (3.9 to 0 Ω) ( p&lt;0.0001). CPB had no additional effect. Heparinisation also reduced the platelet count from 127 (110–170) to 95 (64–117) p=0.023 . The inhibition of macroaggregation could not be reversed by ex vivo heparinase. Volunteers: In vitro, the same heparin concentration, as measured in vivo (4 μ.mL −1), inhibited collagen-induced macroaggregation (20.3 to 14.7 Ω), but this effect was less than that observed ex vivo and was reversed by heparinase. In vitro heparin promoted fMLP macroaggregation (2.9 to 8.6 Ω). The inhibition of macroaggregation resulted from heparinisation, per se, rather than CPB and was insensitive to heparinase. There was less inhibition by in vitro heparin, which was reversible by heparinase, indicating a direct effect of heparin in vitro. The disparate findings are suggestive of an indirect action by heparin in vivo on macroaggregation, although heparin had a small direct stimulatory action on microaggregation.</abstract><cop>New York, NY</cop><pub>Elsevier Ltd</pub><pmid>10822071</pmid><doi>10.1016/S0049-3848(99)00243-1</doi><tpages>8</tpages></addata></record>
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subjects Anticoagulants - pharmacology
Biological and medical sciences
Blood. Blood coagulation. Reticuloendothelial system
Cardiac surgery
Cardiopulmonary Bypass
Collagen
Collagen - pharmacology
Coronary Artery Bypass
Female
fMLP
Heparin - pharmacology
Hirudin
Hirudins - analogs & derivatives
Hirudins - pharmacology
Humans
Leukocytes
Male
Medical sciences
Middle Aged
N-Formylmethionine Leucyl-Phenylalanine - pharmacology
Neutrophils
Pharmacology. Drug treatments
Platelet Aggregation - drug effects
Platelet Aggregation Inhibitors - pharmacology
Platelet Count - drug effects
Platelet Function Tests
Recombinant Proteins - pharmacology
title Heparin, Platelet Aggregation, Neutrophils, and Cardiopulmonary Bypass
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