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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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 |
doi_str_mv | 10.1016/S0049-3848(99)00243-1 |
format | Article |
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−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<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.</description><identifier>ISSN: 0049-3848</identifier><identifier>EISSN: 1879-2472</identifier><identifier>DOI: 10.1016/S0049-3848(99)00243-1</identifier><identifier>PMID: 10822071</identifier><identifier>CODEN: THBRAA</identifier><language>eng</language><publisher>New York, NY: Elsevier Ltd</publisher><subject>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</subject><ispartof>Thrombosis research, 2000-05, Vol.98 (4), p.249-256</ispartof><rights>2000 Elsevier Science Ltd</rights><rights>2000 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c390t-ee377a1226fc427805d13c1b218e74bbac485e5aeb496ccfd7e2484ae64d50813</citedby><cites>FETCH-LOGICAL-c390t-ee377a1226fc427805d13c1b218e74bbac485e5aeb496ccfd7e2484ae64d50813</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0049384899002431$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3536,27903,27904,65309</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1403027$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10822071$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><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><title>Heparin, Platelet Aggregation, Neutrophils, and Cardiopulmonary Bypass</title><title>Thrombosis research</title><addtitle>Thromb Res</addtitle><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<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.</description><subject>Anticoagulants - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Blood. Blood coagulation. 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 & 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 & 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<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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