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Evaluation of automated immunoassays in the diagnosis of heparin induced thrombocytopenia

Abstract Background Heparin-induced thrombocytopenia (HIT) is caused by platelet-activating antibodies that recognize platelet factor 4/heparin (PF4/hep) complexes. The in vitro demonstration of PF4/hep antibodies using functional and immunological methods is essential for optimal management of pati...

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Published in:Thrombosis research 2013-03, Vol.131 (3), p.e85-e90
Main Authors: Althaus, Karina, Hron, Gregor, Strobel, Ulrike, Abbate, Rosanna, Rogolino, Angela, Davidson, Simon, Greinacher, Andreas, Bakchoul, Tamam
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container_title Thrombosis research
container_volume 131
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Strobel, Ulrike
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Rogolino, Angela
Davidson, Simon
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Bakchoul, Tamam
description Abstract Background Heparin-induced thrombocytopenia (HIT) is caused by platelet-activating antibodies that recognize platelet factor 4/heparin (PF4/hep) complexes. The in vitro demonstration of PF4/hep antibodies using functional and immunological methods is essential for optimal management of patients suspected to have HIT. Since functional assays are technically challenging and limited to specialized laboratories, antigen-binding assays are commonly used in routine laboratories. Study Design Blood samples from 448 consecutive patients in whom HIT was suspected were investigated using a latex agglutination test HemosIL® HIT-Ab(PF4-H) (HemosIL-Ab), two chemiluminescence tests HemosIL AcuStar HIT-Ab(PF4-H) (HemosIL AcuStar-Ab) and AcuStar HIT-IgG(PF4-H) (HemosIL AcuStar-IgG), an in-house PF4/hep IgG enzyme immunoassay (EIA) and the heparin induced platelet aggregation (HIPA) test. Results Antibodies against PF4/hep were detectable in 44 out of 119 samples using HemosIL-Ab among which 20 samples were also reactive in the HIPA; and in 122, 64 and 108 out of 448 sera using HemosIL AcuStar-Ab, HemosIL AcuStar-IgG and in-house PF4/hep IgG-EIA, respectively, among which 52 sera were also reactive in the HIPA. All assays had high sensitivities of > 95% for platelet activating antibodies; however, they differed in their specificities. The highest specificity and positive predictive value was observed by HemosIL AcuStar-IgG (96% and 78%, respectively). Conclusion Automated immunoassays are useful in the laboratory investigations of HIT and present a potential improvement toward standardization of laboratory investigations of HIT. The high positive predictive capability may justify treating the patient with alternative anticoagulants without waiting for the results of a functional assay.
doi_str_mv 10.1016/j.thromres.2013.01.005
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The in vitro demonstration of PF4/hep antibodies using functional and immunological methods is essential for optimal management of patients suspected to have HIT. Since functional assays are technically challenging and limited to specialized laboratories, antigen-binding assays are commonly used in routine laboratories. Study Design Blood samples from 448 consecutive patients in whom HIT was suspected were investigated using a latex agglutination test HemosIL® HIT-Ab(PF4-H) (HemosIL-Ab), two chemiluminescence tests HemosIL AcuStar HIT-Ab(PF4-H) (HemosIL AcuStar-Ab) and AcuStar HIT-IgG(PF4-H) (HemosIL AcuStar-IgG), an in-house PF4/hep IgG enzyme immunoassay (EIA) and the heparin induced platelet aggregation (HIPA) test. Results Antibodies against PF4/hep were detectable in 44 out of 119 samples using HemosIL-Ab among which 20 samples were also reactive in the HIPA; and in 122, 64 and 108 out of 448 sera using HemosIL AcuStar-Ab, HemosIL AcuStar-IgG and in-house PF4/hep IgG-EIA, respectively, among which 52 sera were also reactive in the HIPA. All assays had high sensitivities of &gt; 95% for platelet activating antibodies; however, they differed in their specificities. The highest specificity and positive predictive value was observed by HemosIL AcuStar-IgG (96% and 78%, respectively). Conclusion Automated immunoassays are useful in the laboratory investigations of HIT and present a potential improvement toward standardization of laboratory investigations of HIT. The high positive predictive capability may justify treating the patient with alternative anticoagulants without waiting for the results of a functional assay.</description><identifier>ISSN: 0049-3848</identifier><identifier>EISSN: 1879-2472</identifier><identifier>DOI: 10.1016/j.thromres.2013.01.005</identifier><identifier>PMID: 23351665</identifier><language>eng</language><publisher>United States: Elsevier Ltd</publisher><subject>Agglutination ; Automation ; Hematology, Oncology and Palliative Medicine ; Heparin ; Heparin - adverse effects ; Heparin - chemistry ; Humans ; immunoassay ; Immunoassay - methods ; Immunoenzyme Techniques ; Immunoglobulin G - chemistry ; Latex - chemistry ; Luminescence ; Platelet Aggregation ; Predictive Value of Tests ; Reproducibility of Results ; Sensitivity and Specificity ; thrombocytopenia ; Thrombocytopenia - chemically induced ; Thrombocytopenia - diagnosis ; Thrombocytopenia - immunology</subject><ispartof>Thrombosis research, 2013-03, Vol.131 (3), p.e85-e90</ispartof><rights>Elsevier Ltd</rights><rights>2013 Elsevier Ltd</rights><rights>Copyright © 2013 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c489t-f540223f0f0407ef6cf19dc3315ede2ab995fceaee451c7f641f5205bd4971f43</citedby><cites>FETCH-LOGICAL-c489t-f540223f0f0407ef6cf19dc3315ede2ab995fceaee451c7f641f5205bd4971f43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790,27957,27958</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23351665$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Althaus, Karina</creatorcontrib><creatorcontrib>Hron, Gregor</creatorcontrib><creatorcontrib>Strobel, Ulrike</creatorcontrib><creatorcontrib>Abbate, Rosanna</creatorcontrib><creatorcontrib>Rogolino, Angela</creatorcontrib><creatorcontrib>Davidson, Simon</creatorcontrib><creatorcontrib>Greinacher, Andreas</creatorcontrib><creatorcontrib>Bakchoul, Tamam</creatorcontrib><title>Evaluation of automated immunoassays in the diagnosis of heparin induced thrombocytopenia</title><title>Thrombosis research</title><addtitle>Thromb Res</addtitle><description>Abstract Background Heparin-induced thrombocytopenia (HIT) is caused by platelet-activating antibodies that recognize platelet factor 4/heparin (PF4/hep) complexes. The in vitro demonstration of PF4/hep antibodies using functional and immunological methods is essential for optimal management of patients suspected to have HIT. Since functional assays are technically challenging and limited to specialized laboratories, antigen-binding assays are commonly used in routine laboratories. Study Design Blood samples from 448 consecutive patients in whom HIT was suspected were investigated using a latex agglutination test HemosIL® HIT-Ab(PF4-H) (HemosIL-Ab), two chemiluminescence tests HemosIL AcuStar HIT-Ab(PF4-H) (HemosIL AcuStar-Ab) and AcuStar HIT-IgG(PF4-H) (HemosIL AcuStar-IgG), an in-house PF4/hep IgG enzyme immunoassay (EIA) and the heparin induced platelet aggregation (HIPA) test. Results Antibodies against PF4/hep were detectable in 44 out of 119 samples using HemosIL-Ab among which 20 samples were also reactive in the HIPA; and in 122, 64 and 108 out of 448 sera using HemosIL AcuStar-Ab, HemosIL AcuStar-IgG and in-house PF4/hep IgG-EIA, respectively, among which 52 sera were also reactive in the HIPA. All assays had high sensitivities of &gt; 95% for platelet activating antibodies; however, they differed in their specificities. The highest specificity and positive predictive value was observed by HemosIL AcuStar-IgG (96% and 78%, respectively). Conclusion Automated immunoassays are useful in the laboratory investigations of HIT and present a potential improvement toward standardization of laboratory investigations of HIT. The high positive predictive capability may justify treating the patient with alternative anticoagulants without waiting for the results of a functional assay.</description><subject>Agglutination</subject><subject>Automation</subject><subject>Hematology, Oncology and Palliative Medicine</subject><subject>Heparin</subject><subject>Heparin - adverse effects</subject><subject>Heparin - chemistry</subject><subject>Humans</subject><subject>immunoassay</subject><subject>Immunoassay - methods</subject><subject>Immunoenzyme Techniques</subject><subject>Immunoglobulin G - chemistry</subject><subject>Latex - chemistry</subject><subject>Luminescence</subject><subject>Platelet Aggregation</subject><subject>Predictive Value of Tests</subject><subject>Reproducibility of Results</subject><subject>Sensitivity and Specificity</subject><subject>thrombocytopenia</subject><subject>Thrombocytopenia - chemically induced</subject><subject>Thrombocytopenia - diagnosis</subject><subject>Thrombocytopenia - immunology</subject><issn>0049-3848</issn><issn>1879-2472</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><recordid>eNqFkT1vFDEQhi0EIkfgL0Rb0twy44_9aBAoCh9SJAqgoLJ83jHnY9c-7N1I9-_j5RIKGty48PPOjJ9h7AqhRsDmzaGe9ylOiXLNAUUNWAOoJ2yDXdtvuWz5U7YBkP1WdLK7YC9yPgBgi716zi64EAqbRm3Yj5s7My5m9jFU0VVmmeNkZhoqP01LiCZnc8qVD9W8p2rw5meI2ecV3dPRpPLgw7DYEvgzzy7a0xyPFLx5yZ45M2Z69XBfsu8fbr5df9refvn4-fr97dbKrp-3TkngXDhwIKEl11iH_WCFQEUDcbPre-UsGSKp0LaukegUB7UbZN-ik-KSvT7XPab4e6E868lnS-NoAsUlaxQoW5RS8II2Z9SmmHMip4_JTyadNIJeteqDftSqV60aUBetJXj10GPZTTT8jT16LMC7M0Dlp3eeks7WUyhefCI76yH6__d4-08JO_rgrRl_0YnyIS4pFI8adeYa9Nd1uetuUUA5bSfuAcTjo3M</recordid><startdate>20130301</startdate><enddate>20130301</enddate><creator>Althaus, Karina</creator><creator>Hron, Gregor</creator><creator>Strobel, Ulrike</creator><creator>Abbate, Rosanna</creator><creator>Rogolino, Angela</creator><creator>Davidson, Simon</creator><creator>Greinacher, Andreas</creator><creator>Bakchoul, Tamam</creator><general>Elsevier Ltd</general><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>20130301</creationdate><title>Evaluation of automated immunoassays in the diagnosis of heparin induced thrombocytopenia</title><author>Althaus, Karina ; Hron, Gregor ; Strobel, Ulrike ; Abbate, Rosanna ; Rogolino, Angela ; Davidson, Simon ; Greinacher, Andreas ; Bakchoul, Tamam</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c489t-f540223f0f0407ef6cf19dc3315ede2ab995fceaee451c7f641f5205bd4971f43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Agglutination</topic><topic>Automation</topic><topic>Hematology, Oncology and Palliative Medicine</topic><topic>Heparin</topic><topic>Heparin - adverse effects</topic><topic>Heparin - chemistry</topic><topic>Humans</topic><topic>immunoassay</topic><topic>Immunoassay - methods</topic><topic>Immunoenzyme Techniques</topic><topic>Immunoglobulin G - chemistry</topic><topic>Latex - chemistry</topic><topic>Luminescence</topic><topic>Platelet Aggregation</topic><topic>Predictive Value of Tests</topic><topic>Reproducibility of Results</topic><topic>Sensitivity and Specificity</topic><topic>thrombocytopenia</topic><topic>Thrombocytopenia - chemically induced</topic><topic>Thrombocytopenia - diagnosis</topic><topic>Thrombocytopenia - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Althaus, Karina</creatorcontrib><creatorcontrib>Hron, Gregor</creatorcontrib><creatorcontrib>Strobel, Ulrike</creatorcontrib><creatorcontrib>Abbate, Rosanna</creatorcontrib><creatorcontrib>Rogolino, Angela</creatorcontrib><creatorcontrib>Davidson, Simon</creatorcontrib><creatorcontrib>Greinacher, Andreas</creatorcontrib><creatorcontrib>Bakchoul, Tamam</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>Thrombosis research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Althaus, Karina</au><au>Hron, Gregor</au><au>Strobel, Ulrike</au><au>Abbate, Rosanna</au><au>Rogolino, Angela</au><au>Davidson, Simon</au><au>Greinacher, Andreas</au><au>Bakchoul, Tamam</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Evaluation of automated immunoassays in the diagnosis of heparin induced thrombocytopenia</atitle><jtitle>Thrombosis research</jtitle><addtitle>Thromb Res</addtitle><date>2013-03-01</date><risdate>2013</risdate><volume>131</volume><issue>3</issue><spage>e85</spage><epage>e90</epage><pages>e85-e90</pages><issn>0049-3848</issn><eissn>1879-2472</eissn><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><abstract>Abstract Background Heparin-induced thrombocytopenia (HIT) is caused by platelet-activating antibodies that recognize platelet factor 4/heparin (PF4/hep) complexes. The in vitro demonstration of PF4/hep antibodies using functional and immunological methods is essential for optimal management of patients suspected to have HIT. Since functional assays are technically challenging and limited to specialized laboratories, antigen-binding assays are commonly used in routine laboratories. Study Design Blood samples from 448 consecutive patients in whom HIT was suspected were investigated using a latex agglutination test HemosIL® HIT-Ab(PF4-H) (HemosIL-Ab), two chemiluminescence tests HemosIL AcuStar HIT-Ab(PF4-H) (HemosIL AcuStar-Ab) and AcuStar HIT-IgG(PF4-H) (HemosIL AcuStar-IgG), an in-house PF4/hep IgG enzyme immunoassay (EIA) and the heparin induced platelet aggregation (HIPA) test. Results Antibodies against PF4/hep were detectable in 44 out of 119 samples using HemosIL-Ab among which 20 samples were also reactive in the HIPA; and in 122, 64 and 108 out of 448 sera using HemosIL AcuStar-Ab, HemosIL AcuStar-IgG and in-house PF4/hep IgG-EIA, respectively, among which 52 sera were also reactive in the HIPA. All assays had high sensitivities of &gt; 95% for platelet activating antibodies; however, they differed in their specificities. The highest specificity and positive predictive value was observed by HemosIL AcuStar-IgG (96% and 78%, respectively). Conclusion Automated immunoassays are useful in the laboratory investigations of HIT and present a potential improvement toward standardization of laboratory investigations of HIT. The high positive predictive capability may justify treating the patient with alternative anticoagulants without waiting for the results of a functional assay.</abstract><cop>United States</cop><pub>Elsevier Ltd</pub><pmid>23351665</pmid><doi>10.1016/j.thromres.2013.01.005</doi></addata></record>
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subjects Agglutination
Automation
Hematology, Oncology and Palliative Medicine
Heparin
Heparin - adverse effects
Heparin - chemistry
Humans
immunoassay
Immunoassay - methods
Immunoenzyme Techniques
Immunoglobulin G - chemistry
Latex - chemistry
Luminescence
Platelet Aggregation
Predictive Value of Tests
Reproducibility of Results
Sensitivity and Specificity
thrombocytopenia
Thrombocytopenia - chemically induced
Thrombocytopenia - diagnosis
Thrombocytopenia - immunology
title Evaluation of automated immunoassays in the diagnosis of heparin induced thrombocytopenia
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