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Platelet transfusion reverses bleeding evoked by triple anti-platelet therapy including vorapaxar, a novel platelet thrombin receptor antagonist
Vorapaxar is a novel protease-activated receptor-1 (PAR-1) antagonist recently approved for the reduction of thrombotic cardiovascular events in patients with a history of myocardial infarction or with peripheral arterial disease. Patients who received vorapaxar in addition to standard of care antip...
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| Published in: | European journal of pharmacology 2015-07, Vol.758, p.107-114 |
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| Main Authors: | , , , , , , , , |
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| cites | cdi_FETCH-LOGICAL-c362t-6eed43620ed2a8d597eff59e08b114a1bb111ea9d660d288aa1f3a11958a515b3 |
| container_end_page | 114 |
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| container_start_page | 107 |
| container_title | European journal of pharmacology |
| container_volume | 758 |
| creator | Cai, Tian-Quan Wickham, L. Alexandra Sitko, Gary Michener, Maria Strainer Raubertas, Richard Handt, Larry Chintala, Madhu Seiffert, Dietmar Forrest, Michael |
| description | Vorapaxar is a novel protease-activated receptor-1 (PAR-1) antagonist recently approved for the reduction of thrombotic cardiovascular events in patients with a history of myocardial infarction or with peripheral arterial disease. Patients who received vorapaxar in addition to standard of care antiplatelet therapy had an increased incidence of major bleeding events compared with placebo. To assess whether platelet transfusion can restore hemostasis in primates on triple antiplatelet therapy, template bleeding times were assessed concurrently in the buccal mucosa, finger pad, and distolateral tail of anesthetized cynomolgus macaques to evaluate bleeding with vorapaxar as either monotherapy or in combination with aspirin or aspirin and clopidogrel. Aspirin (5mg/kg, IV) or vorapaxar (1mg/kg, PO) alone had no significant effect on bleeding times in the three vascular beds examined. A modest ( |
| doi_str_mv | 10.1016/j.ejphar.2015.03.073 |
| format | article |
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Alexandra ; Sitko, Gary ; Michener, Maria Strainer ; Raubertas, Richard ; Handt, Larry ; Chintala, Madhu ; Seiffert, Dietmar ; Forrest, Michael</creator><creatorcontrib>Cai, Tian-Quan ; Wickham, L. Alexandra ; Sitko, Gary ; Michener, Maria Strainer ; Raubertas, Richard ; Handt, Larry ; Chintala, Madhu ; Seiffert, Dietmar ; Forrest, Michael</creatorcontrib><description>Vorapaxar is a novel protease-activated receptor-1 (PAR-1) antagonist recently approved for the reduction of thrombotic cardiovascular events in patients with a history of myocardial infarction or with peripheral arterial disease. Patients who received vorapaxar in addition to standard of care antiplatelet therapy had an increased incidence of major bleeding events compared with placebo. To assess whether platelet transfusion can restore hemostasis in primates on triple antiplatelet therapy, template bleeding times were assessed concurrently in the buccal mucosa, finger pad, and distolateral tail of anesthetized cynomolgus macaques to evaluate bleeding with vorapaxar as either monotherapy or in combination with aspirin or aspirin and clopidogrel. Aspirin (5mg/kg, IV) or vorapaxar (1mg/kg, PO) alone had no significant effect on bleeding times in the three vascular beds examined. A modest (<2-fold) increase in bleeding time was achieved in the three beds with the dual combination of aspirin and vorapaxar. Major increases in bleeding time were achieved in the three beds with the triple combination of aspirin (5mg/kg, IV), vorapaxar (1mg/kg, PO), and clopidogrel (1mg/kg, PO). Transfusion of fresh human platelet rich plasma, but not platelet poor plasma, reversed the increase in bleeding time in the triple therapy group. Transfusion of human platelets may be a viable approach in situations requiring a rapid reversal of platelet function in individuals treated with triple anti-platelet therapy that includes vorapaxar.</description><identifier>ISSN: 0014-2999</identifier><identifier>EISSN: 1879-0712</identifier><identifier>DOI: 10.1016/j.ejphar.2015.03.073</identifier><identifier>PMID: 25857224</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject><![CDATA[Animals ; Aspirin ; Aspirin - administration & dosage ; Aspirin - adverse effects ; Bleeding Time ; Blood platelets ; Clopidogrel ; Drug Therapy, Combination - adverse effects ; Hemorrhage ; Hemorrhage - chemically induced ; Hemorrhage - therapy ; Humans ; Lactones - administration & dosage ; Lactones - adverse effects ; Macaca fascicularis ; Platelet Aggregation Inhibitors - administration & dosage ; Platelet Aggregation Inhibitors - adverse effects ; Platelet Transfusion ; Pyridines - administration & dosage ; Pyridines - adverse effects ; Receptors, Thrombin - antagonists & inhibitors ; Ticlopidine - administration & dosage ; Ticlopidine - adverse effects ; Ticlopidine - analogs & derivatives ; Vorapaxar]]></subject><ispartof>European journal of pharmacology, 2015-07, Vol.758, p.107-114</ispartof><rights>2015 Elsevier B.V.</rights><rights>Copyright © 2015 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c362t-6eed43620ed2a8d597eff59e08b114a1bb111ea9d660d288aa1f3a11958a515b3</citedby><cites>FETCH-LOGICAL-c362t-6eed43620ed2a8d597eff59e08b114a1bb111ea9d660d288aa1f3a11958a515b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25857224$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cai, Tian-Quan</creatorcontrib><creatorcontrib>Wickham, L. Alexandra</creatorcontrib><creatorcontrib>Sitko, Gary</creatorcontrib><creatorcontrib>Michener, Maria Strainer</creatorcontrib><creatorcontrib>Raubertas, Richard</creatorcontrib><creatorcontrib>Handt, Larry</creatorcontrib><creatorcontrib>Chintala, Madhu</creatorcontrib><creatorcontrib>Seiffert, Dietmar</creatorcontrib><creatorcontrib>Forrest, Michael</creatorcontrib><title>Platelet transfusion reverses bleeding evoked by triple anti-platelet therapy including vorapaxar, a novel platelet thrombin receptor antagonist</title><title>European journal of pharmacology</title><addtitle>Eur J Pharmacol</addtitle><description>Vorapaxar is a novel protease-activated receptor-1 (PAR-1) antagonist recently approved for the reduction of thrombotic cardiovascular events in patients with a history of myocardial infarction or with peripheral arterial disease. Patients who received vorapaxar in addition to standard of care antiplatelet therapy had an increased incidence of major bleeding events compared with placebo. To assess whether platelet transfusion can restore hemostasis in primates on triple antiplatelet therapy, template bleeding times were assessed concurrently in the buccal mucosa, finger pad, and distolateral tail of anesthetized cynomolgus macaques to evaluate bleeding with vorapaxar as either monotherapy or in combination with aspirin or aspirin and clopidogrel. Aspirin (5mg/kg, IV) or vorapaxar (1mg/kg, PO) alone had no significant effect on bleeding times in the three vascular beds examined. A modest (<2-fold) increase in bleeding time was achieved in the three beds with the dual combination of aspirin and vorapaxar. Major increases in bleeding time were achieved in the three beds with the triple combination of aspirin (5mg/kg, IV), vorapaxar (1mg/kg, PO), and clopidogrel (1mg/kg, PO). Transfusion of fresh human platelet rich plasma, but not platelet poor plasma, reversed the increase in bleeding time in the triple therapy group. Transfusion of human platelets may be a viable approach in situations requiring a rapid reversal of platelet function in individuals treated with triple anti-platelet therapy that includes vorapaxar.</description><subject>Animals</subject><subject>Aspirin</subject><subject>Aspirin - administration & dosage</subject><subject>Aspirin - adverse effects</subject><subject>Bleeding Time</subject><subject>Blood platelets</subject><subject>Clopidogrel</subject><subject>Drug Therapy, Combination - adverse effects</subject><subject>Hemorrhage</subject><subject>Hemorrhage - chemically induced</subject><subject>Hemorrhage - therapy</subject><subject>Humans</subject><subject>Lactones - administration & dosage</subject><subject>Lactones - adverse effects</subject><subject>Macaca fascicularis</subject><subject>Platelet Aggregation Inhibitors - administration & dosage</subject><subject>Platelet Aggregation Inhibitors - adverse effects</subject><subject>Platelet Transfusion</subject><subject>Pyridines - administration & dosage</subject><subject>Pyridines - adverse effects</subject><subject>Receptors, Thrombin - antagonists & inhibitors</subject><subject>Ticlopidine - administration & dosage</subject><subject>Ticlopidine - adverse effects</subject><subject>Ticlopidine - analogs & derivatives</subject><subject>Vorapaxar</subject><issn>0014-2999</issn><issn>1879-0712</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><recordid>eNp9kU-P1SAUxYnROM_Rb2AMSxe2Ai0tbEzMxH_JJLrQNbltb2d48qACbXzfwo8szzdOXLm6hPzOPXAOIc85qznj3et9jfvlFmItGJc1a2rWNw_IjqteV6zn4iHZMcbbSmitL8iTlPaMMamFfEwuhFSyF6LdkV9fHGR0mGmO4NO8Jhs8jbhhTJjo4BAn628obuE7TnQ4Fs4uDin4bKvlXnyLEZYjtX506x_BFsoF_IT4igL1YUNH_6FjOAz25DPikkM8bYOb4G3KT8mjGVzCZ3fzknx7_-7r1cfq-vOHT1dvr6ux6USuuvKutpwYTgLUJHWP8yw1MjVw3gIfyuAIeuo6NgmlAPjcAOdaKpBcDs0leXneu8TwY8WUzcGmEZ0Dj2FNhneK8b5jUhW0PaNjDClFnM0S7QHi0XBmTl2YvTl3YU5dGNaY0kWRvbhzWIcDTveiv-EX4M0ZwPLPzWI0abTox5J4CSabKdj_O_wGYDGg7Q</recordid><startdate>20150705</startdate><enddate>20150705</enddate><creator>Cai, Tian-Quan</creator><creator>Wickham, L. 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Alexandra</creatorcontrib><creatorcontrib>Sitko, Gary</creatorcontrib><creatorcontrib>Michener, Maria Strainer</creatorcontrib><creatorcontrib>Raubertas, Richard</creatorcontrib><creatorcontrib>Handt, Larry</creatorcontrib><creatorcontrib>Chintala, Madhu</creatorcontrib><creatorcontrib>Seiffert, Dietmar</creatorcontrib><creatorcontrib>Forrest, Michael</creatorcontrib><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>European journal of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cai, Tian-Quan</au><au>Wickham, L. Alexandra</au><au>Sitko, Gary</au><au>Michener, Maria Strainer</au><au>Raubertas, Richard</au><au>Handt, Larry</au><au>Chintala, Madhu</au><au>Seiffert, Dietmar</au><au>Forrest, Michael</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Platelet transfusion reverses bleeding evoked by triple anti-platelet therapy including vorapaxar, a novel platelet thrombin receptor antagonist</atitle><jtitle>European journal of pharmacology</jtitle><addtitle>Eur J Pharmacol</addtitle><date>2015-07-05</date><risdate>2015</risdate><volume>758</volume><spage>107</spage><epage>114</epage><pages>107-114</pages><issn>0014-2999</issn><eissn>1879-0712</eissn><abstract>Vorapaxar is a novel protease-activated receptor-1 (PAR-1) antagonist recently approved for the reduction of thrombotic cardiovascular events in patients with a history of myocardial infarction or with peripheral arterial disease. Patients who received vorapaxar in addition to standard of care antiplatelet therapy had an increased incidence of major bleeding events compared with placebo. To assess whether platelet transfusion can restore hemostasis in primates on triple antiplatelet therapy, template bleeding times were assessed concurrently in the buccal mucosa, finger pad, and distolateral tail of anesthetized cynomolgus macaques to evaluate bleeding with vorapaxar as either monotherapy or in combination with aspirin or aspirin and clopidogrel. Aspirin (5mg/kg, IV) or vorapaxar (1mg/kg, PO) alone had no significant effect on bleeding times in the three vascular beds examined. A modest (<2-fold) increase in bleeding time was achieved in the three beds with the dual combination of aspirin and vorapaxar. Major increases in bleeding time were achieved in the three beds with the triple combination of aspirin (5mg/kg, IV), vorapaxar (1mg/kg, PO), and clopidogrel (1mg/kg, PO). Transfusion of fresh human platelet rich plasma, but not platelet poor plasma, reversed the increase in bleeding time in the triple therapy group. Transfusion of human platelets may be a viable approach in situations requiring a rapid reversal of platelet function in individuals treated with triple anti-platelet therapy that includes vorapaxar.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>25857224</pmid><doi>10.1016/j.ejphar.2015.03.073</doi><tpages>8</tpages></addata></record> |
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| identifier | ISSN: 0014-2999 |
| ispartof | European journal of pharmacology, 2015-07, Vol.758, p.107-114 |
| issn | 0014-2999 1879-0712 |
| language | eng |
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| source | ScienceDirect Freedom Collection 2022-2024 |
| subjects | Animals Aspirin Aspirin - administration & dosage Aspirin - adverse effects Bleeding Time Blood platelets Clopidogrel Drug Therapy, Combination - adverse effects Hemorrhage Hemorrhage - chemically induced Hemorrhage - therapy Humans Lactones - administration & dosage Lactones - adverse effects Macaca fascicularis Platelet Aggregation Inhibitors - administration & dosage Platelet Aggregation Inhibitors - adverse effects Platelet Transfusion Pyridines - administration & dosage Pyridines - adverse effects Receptors, Thrombin - antagonists & inhibitors Ticlopidine - administration & dosage Ticlopidine - adverse effects Ticlopidine - analogs & derivatives Vorapaxar |
| title | Platelet transfusion reverses bleeding evoked by triple anti-platelet therapy including vorapaxar, a novel platelet thrombin receptor antagonist |
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