Frequency of positive anti-PF4/polyanion antibody tests after COVID-19 vaccination with ChAdOx1 nCoV-19 and BNT162b2
Vaccination using the adenoviral vector COVID-19 vaccine ChAdOx1 nCoV-19 (AstraZeneca) has been associated with rare vaccine-induced immune thrombotic thrombocytopenia (VITT). Affected patients test strongly positive in platelet factor 4 (PF4)/polyanion enzyme immunoassays (EIAs), and serum-induced...
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| Veröffentlicht in: | Blood 2021-07, Vol.138 (4), p.299-303 |
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| creator | Thiele, Thomas Ulm, Lena Holtfreter, Silva Schönborn, Linda Kuhn, Sven Olaf Scheer, Christian Warkentin, Theodore E. Bröker, Barbara M. Becker, Karsten Aurich, Konstanze Selleng, Kathleen Hübner, Nils-Olaf Greinacher, Andreas |
| description | Vaccination using the adenoviral vector COVID-19 vaccine ChAdOx1 nCoV-19 (AstraZeneca) has been associated with rare vaccine-induced immune thrombotic thrombocytopenia (VITT). Affected patients test strongly positive in platelet factor 4 (PF4)/polyanion enzyme immunoassays (EIAs), and serum-induced platelet activation is maximal in the presence of PF4. We determined the frequency of anti-PF4/polyanion antibodies in healthy vaccinees and assessed whether PF4/polyanion EIA+ sera exhibit platelet-activating properties after vaccination with ChAdOx1 nCoV-19 (n = 138) or BNT162b2 (BioNTech/Pfizer; n = 143). In total, 19 of 281 participants tested positive for anti-PF4/polyanion antibodies postvaccination (All: 6.8% [95% confidence interval (CI), 4.4-10.3]; BNT162b2: 5.6% [95% CI, 2.9-10.7]; ChAdOx1 nCoV-19: 8.0% [95% CI, 4.5% to 13.7%]). Optical densities were mostly low (between 0.5 and 1.0 units; reference range, |
| doi_str_mv | 10.1182/blood.2021012217 |
| format | Article |
| fullrecord | <record><control><sourceid>elsevier_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8129797</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0006497121010624</els_id><sourcerecordid>S0006497121010624</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3981-a8bfa37e16733886ff80651e2d60e166b64332479e3ec400f117518d128992383</originalsourceid><addsrcrecordid>eNp1UcFuEzEQtRCIhsKdE_IPbDtjb3a9HJDKltBKFeFQerW89iwxSu1gu4H8PZumFDhwGmnmvTdv5jH2GuEEUYnTYR2jOxEgEFAIbJ-wGc6FqgAEPGUzAGiqumvxiL3I-RsA1lLMn7MjKTulGqVmrCwSfb-jYHc8jnwTsy9-S9yE4qvPi_p0E9c7E3wM960huh0vlEvmZiyUeL-8uTyvsONbY60PpuyRP3xZ8X515pY_kYc-3uwBJjj-_tM1NmIQL9mz0awzvXqox-zL4sN1f1FdLT9e9mdXlZ38YWXUMBrZEjatlJPfcVTQzJGEa2BqNkNTSynqtiNJtgYYEds5KodCdZ2QSh6zdwfdzd1wS85SKMms9Sb5W5N2Ohqv_50Ev9Jf41YrFF3btZMAHARsijknGh-5CHqfgL5PQP9JYKK8-XvnI-H3yyfA2wOApsu3npLO1k8BkPOJbNEu-v-r_wLEUZRy</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Frequency of positive anti-PF4/polyanion antibody tests after COVID-19 vaccination with ChAdOx1 nCoV-19 and BNT162b2</title><source>MEDLINE</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Alma/SFX Local Collection</source><creator>Thiele, Thomas ; Ulm, Lena ; Holtfreter, Silva ; Schönborn, Linda ; Kuhn, Sven Olaf ; Scheer, Christian ; Warkentin, Theodore E. ; Bröker, Barbara M. ; Becker, Karsten ; Aurich, Konstanze ; Selleng, Kathleen ; Hübner, Nils-Olaf ; Greinacher, Andreas</creator><creatorcontrib>Thiele, Thomas ; Ulm, Lena ; Holtfreter, Silva ; Schönborn, Linda ; Kuhn, Sven Olaf ; Scheer, Christian ; Warkentin, Theodore E. ; Bröker, Barbara M. ; Becker, Karsten ; Aurich, Konstanze ; Selleng, Kathleen ; Hübner, Nils-Olaf ; Greinacher, Andreas</creatorcontrib><description>Vaccination using the adenoviral vector COVID-19 vaccine ChAdOx1 nCoV-19 (AstraZeneca) has been associated with rare vaccine-induced immune thrombotic thrombocytopenia (VITT). Affected patients test strongly positive in platelet factor 4 (PF4)/polyanion enzyme immunoassays (EIAs), and serum-induced platelet activation is maximal in the presence of PF4. We determined the frequency of anti-PF4/polyanion antibodies in healthy vaccinees and assessed whether PF4/polyanion EIA+ sera exhibit platelet-activating properties after vaccination with ChAdOx1 nCoV-19 (n = 138) or BNT162b2 (BioNTech/Pfizer; n = 143). In total, 19 of 281 participants tested positive for anti-PF4/polyanion antibodies postvaccination (All: 6.8% [95% confidence interval (CI), 4.4-10.3]; BNT162b2: 5.6% [95% CI, 2.9-10.7]; ChAdOx1 nCoV-19: 8.0% [95% CI, 4.5% to 13.7%]). Optical densities were mostly low (between 0.5 and 1.0 units; reference range, <0.50), and none of the PF4/polyanion EIA+ samples induced platelet activation in the presence of PF4. We conclude that positive PF4/polyanion EIAs can occur after severe acute respiratory syndrome coronavirus 2 vaccination with both messenger RNA- and adenoviral vector-based vaccines, but many of these antibodies likely have minor (if any) clinical relevance. Accordingly, low-titer positive PF4/polyanion EIA results should be interpreted with caution when screening asymptomatic individuals after vaccination against COVID-19. Pathogenic platelet-activating antibodies that cause VITT do not occur commonly following vaccination.
•Low-titer PF4/polyanion antibodies occur after vaccination with ChAdOx1 nCoV-19 and BNT162b2.•These PF4/polyanion antibodies do not activate platelets and may have little relevance for the diagnosis of VITT.
[Display omitted]</description><identifier>ISSN: 0006-4971</identifier><identifier>EISSN: 1528-0020</identifier><identifier>DOI: 10.1182/blood.2021012217</identifier><identifier>PMID: 33988688</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adult ; Asymptomatic Diseases ; Autoantibodies - blood ; Autoantibodies - immunology ; BNT162 Vaccine ; Brief Report ; ChAdOx1 nCoV-19 ; Clinical Trials and Observations ; COVID-19 - prevention & control ; COVID-19 Vaccines - adverse effects ; Female ; Free s ; Health Personnel ; Humans ; Immunoenzyme Techniques ; Immunoglobulin G - blood ; Immunoglobulin G - immunology ; Male ; Middle Aged ; Platelet Activation ; Platelet Factor 4 - immunology ; Polyelectrolytes ; Purpura, Thrombotic Thrombocytopenic - etiology ; Purpura, Thrombotic Thrombocytopenic - immunology ; Seroconversion ; Thrombocytopenia ; Thrombophilia - etiology ; Thrombosis and Hemostasis ; Vaccination - adverse effects</subject><ispartof>Blood, 2021-07, Vol.138 (4), p.299-303</ispartof><rights>2021 American Society of Hematology</rights><rights>2021 by The American Society of Hematology.</rights><rights>2021 by The American Society of Hematology 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3981-a8bfa37e16733886ff80651e2d60e166b64332479e3ec400f117518d128992383</citedby><cites>FETCH-LOGICAL-c3981-a8bfa37e16733886ff80651e2d60e166b64332479e3ec400f117518d128992383</cites><orcidid>0000-0003-3365-0168 ; 0000-0002-6660-9949 ; 0000-0002-5020-8542 ; 0000-0002-6391-1341 ; 0000-0002-2672-8230 ; 0000-0002-3388-8785 ; 0000-0002-8046-7588 ; 0000-0001-6171-8874 ; 0000-0001-8343-7336</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27923,27924</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33988688$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Thiele, Thomas</creatorcontrib><creatorcontrib>Ulm, Lena</creatorcontrib><creatorcontrib>Holtfreter, Silva</creatorcontrib><creatorcontrib>Schönborn, Linda</creatorcontrib><creatorcontrib>Kuhn, Sven Olaf</creatorcontrib><creatorcontrib>Scheer, Christian</creatorcontrib><creatorcontrib>Warkentin, Theodore E.</creatorcontrib><creatorcontrib>Bröker, Barbara M.</creatorcontrib><creatorcontrib>Becker, Karsten</creatorcontrib><creatorcontrib>Aurich, Konstanze</creatorcontrib><creatorcontrib>Selleng, Kathleen</creatorcontrib><creatorcontrib>Hübner, Nils-Olaf</creatorcontrib><creatorcontrib>Greinacher, Andreas</creatorcontrib><title>Frequency of positive anti-PF4/polyanion antibody tests after COVID-19 vaccination with ChAdOx1 nCoV-19 and BNT162b2</title><title>Blood</title><addtitle>Blood</addtitle><description>Vaccination using the adenoviral vector COVID-19 vaccine ChAdOx1 nCoV-19 (AstraZeneca) has been associated with rare vaccine-induced immune thrombotic thrombocytopenia (VITT). Affected patients test strongly positive in platelet factor 4 (PF4)/polyanion enzyme immunoassays (EIAs), and serum-induced platelet activation is maximal in the presence of PF4. We determined the frequency of anti-PF4/polyanion antibodies in healthy vaccinees and assessed whether PF4/polyanion EIA+ sera exhibit platelet-activating properties after vaccination with ChAdOx1 nCoV-19 (n = 138) or BNT162b2 (BioNTech/Pfizer; n = 143). In total, 19 of 281 participants tested positive for anti-PF4/polyanion antibodies postvaccination (All: 6.8% [95% confidence interval (CI), 4.4-10.3]; BNT162b2: 5.6% [95% CI, 2.9-10.7]; ChAdOx1 nCoV-19: 8.0% [95% CI, 4.5% to 13.7%]). Optical densities were mostly low (between 0.5 and 1.0 units; reference range, <0.50), and none of the PF4/polyanion EIA+ samples induced platelet activation in the presence of PF4. We conclude that positive PF4/polyanion EIAs can occur after severe acute respiratory syndrome coronavirus 2 vaccination with both messenger RNA- and adenoviral vector-based vaccines, but many of these antibodies likely have minor (if any) clinical relevance. Accordingly, low-titer positive PF4/polyanion EIA results should be interpreted with caution when screening asymptomatic individuals after vaccination against COVID-19. Pathogenic platelet-activating antibodies that cause VITT do not occur commonly following vaccination.
•Low-titer PF4/polyanion antibodies occur after vaccination with ChAdOx1 nCoV-19 and BNT162b2.•These PF4/polyanion antibodies do not activate platelets and may have little relevance for the diagnosis of VITT.
[Display omitted]</description><subject>Adult</subject><subject>Asymptomatic Diseases</subject><subject>Autoantibodies - blood</subject><subject>Autoantibodies - immunology</subject><subject>BNT162 Vaccine</subject><subject>Brief Report</subject><subject>ChAdOx1 nCoV-19</subject><subject>Clinical Trials and Observations</subject><subject>COVID-19 - prevention & control</subject><subject>COVID-19 Vaccines - adverse effects</subject><subject>Female</subject><subject>Free s</subject><subject>Health Personnel</subject><subject>Humans</subject><subject>Immunoenzyme Techniques</subject><subject>Immunoglobulin G - blood</subject><subject>Immunoglobulin G - immunology</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Platelet Activation</subject><subject>Platelet Factor 4 - immunology</subject><subject>Polyelectrolytes</subject><subject>Purpura, Thrombotic Thrombocytopenic - etiology</subject><subject>Purpura, Thrombotic Thrombocytopenic - immunology</subject><subject>Seroconversion</subject><subject>Thrombocytopenia</subject><subject>Thrombophilia - etiology</subject><subject>Thrombosis and Hemostasis</subject><subject>Vaccination - adverse effects</subject><issn>0006-4971</issn><issn>1528-0020</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1UcFuEzEQtRCIhsKdE_IPbDtjb3a9HJDKltBKFeFQerW89iwxSu1gu4H8PZumFDhwGmnmvTdv5jH2GuEEUYnTYR2jOxEgEFAIbJ-wGc6FqgAEPGUzAGiqumvxiL3I-RsA1lLMn7MjKTulGqVmrCwSfb-jYHc8jnwTsy9-S9yE4qvPi_p0E9c7E3wM960huh0vlEvmZiyUeL-8uTyvsONbY60PpuyRP3xZ8X515pY_kYc-3uwBJjj-_tM1NmIQL9mz0awzvXqox-zL4sN1f1FdLT9e9mdXlZ38YWXUMBrZEjatlJPfcVTQzJGEa2BqNkNTSynqtiNJtgYYEds5KodCdZ2QSh6zdwfdzd1wS85SKMms9Sb5W5N2Ohqv_50Ev9Jf41YrFF3btZMAHARsijknGh-5CHqfgL5PQP9JYKK8-XvnI-H3yyfA2wOApsu3npLO1k8BkPOJbNEu-v-r_wLEUZRy</recordid><startdate>20210729</startdate><enddate>20210729</enddate><creator>Thiele, Thomas</creator><creator>Ulm, Lena</creator><creator>Holtfreter, Silva</creator><creator>Schönborn, Linda</creator><creator>Kuhn, Sven Olaf</creator><creator>Scheer, Christian</creator><creator>Warkentin, Theodore E.</creator><creator>Bröker, Barbara M.</creator><creator>Becker, Karsten</creator><creator>Aurich, Konstanze</creator><creator>Selleng, Kathleen</creator><creator>Hübner, Nils-Olaf</creator><creator>Greinacher, Andreas</creator><general>Elsevier Inc</general><general>American Society of Hematology</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>5PM</scope><orcidid>https://orcid.org/0000-0003-3365-0168</orcidid><orcidid>https://orcid.org/0000-0002-6660-9949</orcidid><orcidid>https://orcid.org/0000-0002-5020-8542</orcidid><orcidid>https://orcid.org/0000-0002-6391-1341</orcidid><orcidid>https://orcid.org/0000-0002-2672-8230</orcidid><orcidid>https://orcid.org/0000-0002-3388-8785</orcidid><orcidid>https://orcid.org/0000-0002-8046-7588</orcidid><orcidid>https://orcid.org/0000-0001-6171-8874</orcidid><orcidid>https://orcid.org/0000-0001-8343-7336</orcidid></search><sort><creationdate>20210729</creationdate><title>Frequency of positive anti-PF4/polyanion antibody tests after COVID-19 vaccination with ChAdOx1 nCoV-19 and BNT162b2</title><author>Thiele, Thomas ; Ulm, Lena ; Holtfreter, Silva ; Schönborn, Linda ; Kuhn, Sven Olaf ; Scheer, Christian ; Warkentin, Theodore E. ; Bröker, Barbara M. ; Becker, Karsten ; Aurich, Konstanze ; Selleng, Kathleen ; Hübner, Nils-Olaf ; Greinacher, Andreas</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3981-a8bfa37e16733886ff80651e2d60e166b64332479e3ec400f117518d128992383</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Adult</topic><topic>Asymptomatic Diseases</topic><topic>Autoantibodies - blood</topic><topic>Autoantibodies - immunology</topic><topic>BNT162 Vaccine</topic><topic>Brief Report</topic><topic>ChAdOx1 nCoV-19</topic><topic>Clinical Trials and Observations</topic><topic>COVID-19 - prevention & control</topic><topic>COVID-19 Vaccines - adverse effects</topic><topic>Female</topic><topic>Free s</topic><topic>Health Personnel</topic><topic>Humans</topic><topic>Immunoenzyme Techniques</topic><topic>Immunoglobulin G - blood</topic><topic>Immunoglobulin G - immunology</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Platelet Activation</topic><topic>Platelet Factor 4 - immunology</topic><topic>Polyelectrolytes</topic><topic>Purpura, Thrombotic Thrombocytopenic - etiology</topic><topic>Purpura, Thrombotic Thrombocytopenic - immunology</topic><topic>Seroconversion</topic><topic>Thrombocytopenia</topic><topic>Thrombophilia - etiology</topic><topic>Thrombosis and Hemostasis</topic><topic>Vaccination - adverse effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Thiele, Thomas</creatorcontrib><creatorcontrib>Ulm, Lena</creatorcontrib><creatorcontrib>Holtfreter, Silva</creatorcontrib><creatorcontrib>Schönborn, Linda</creatorcontrib><creatorcontrib>Kuhn, Sven Olaf</creatorcontrib><creatorcontrib>Scheer, Christian</creatorcontrib><creatorcontrib>Warkentin, Theodore E.</creatorcontrib><creatorcontrib>Bröker, Barbara M.</creatorcontrib><creatorcontrib>Becker, Karsten</creatorcontrib><creatorcontrib>Aurich, Konstanze</creatorcontrib><creatorcontrib>Selleng, Kathleen</creatorcontrib><creatorcontrib>Hübner, Nils-Olaf</creatorcontrib><creatorcontrib>Greinacher, Andreas</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Blood</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Thiele, Thomas</au><au>Ulm, Lena</au><au>Holtfreter, Silva</au><au>Schönborn, Linda</au><au>Kuhn, Sven Olaf</au><au>Scheer, Christian</au><au>Warkentin, Theodore E.</au><au>Bröker, Barbara M.</au><au>Becker, Karsten</au><au>Aurich, Konstanze</au><au>Selleng, Kathleen</au><au>Hübner, Nils-Olaf</au><au>Greinacher, Andreas</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Frequency of positive anti-PF4/polyanion antibody tests after COVID-19 vaccination with ChAdOx1 nCoV-19 and BNT162b2</atitle><jtitle>Blood</jtitle><addtitle>Blood</addtitle><date>2021-07-29</date><risdate>2021</risdate><volume>138</volume><issue>4</issue><spage>299</spage><epage>303</epage><pages>299-303</pages><issn>0006-4971</issn><eissn>1528-0020</eissn><abstract>Vaccination using the adenoviral vector COVID-19 vaccine ChAdOx1 nCoV-19 (AstraZeneca) has been associated with rare vaccine-induced immune thrombotic thrombocytopenia (VITT). Affected patients test strongly positive in platelet factor 4 (PF4)/polyanion enzyme immunoassays (EIAs), and serum-induced platelet activation is maximal in the presence of PF4. We determined the frequency of anti-PF4/polyanion antibodies in healthy vaccinees and assessed whether PF4/polyanion EIA+ sera exhibit platelet-activating properties after vaccination with ChAdOx1 nCoV-19 (n = 138) or BNT162b2 (BioNTech/Pfizer; n = 143). In total, 19 of 281 participants tested positive for anti-PF4/polyanion antibodies postvaccination (All: 6.8% [95% confidence interval (CI), 4.4-10.3]; BNT162b2: 5.6% [95% CI, 2.9-10.7]; ChAdOx1 nCoV-19: 8.0% [95% CI, 4.5% to 13.7%]). Optical densities were mostly low (between 0.5 and 1.0 units; reference range, <0.50), and none of the PF4/polyanion EIA+ samples induced platelet activation in the presence of PF4. We conclude that positive PF4/polyanion EIAs can occur after severe acute respiratory syndrome coronavirus 2 vaccination with both messenger RNA- and adenoviral vector-based vaccines, but many of these antibodies likely have minor (if any) clinical relevance. Accordingly, low-titer positive PF4/polyanion EIA results should be interpreted with caution when screening asymptomatic individuals after vaccination against COVID-19. Pathogenic platelet-activating antibodies that cause VITT do not occur commonly following vaccination.
•Low-titer PF4/polyanion antibodies occur after vaccination with ChAdOx1 nCoV-19 and BNT162b2.•These PF4/polyanion antibodies do not activate platelets and may have little relevance for the diagnosis of VITT.
[Display omitted]</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>33988688</pmid><doi>10.1182/blood.2021012217</doi><tpages>5</tpages><orcidid>https://orcid.org/0000-0003-3365-0168</orcidid><orcidid>https://orcid.org/0000-0002-6660-9949</orcidid><orcidid>https://orcid.org/0000-0002-5020-8542</orcidid><orcidid>https://orcid.org/0000-0002-6391-1341</orcidid><orcidid>https://orcid.org/0000-0002-2672-8230</orcidid><orcidid>https://orcid.org/0000-0002-3388-8785</orcidid><orcidid>https://orcid.org/0000-0002-8046-7588</orcidid><orcidid>https://orcid.org/0000-0001-6171-8874</orcidid><orcidid>https://orcid.org/0000-0001-8343-7336</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Blood, 2021-07, Vol.138 (4), p.299-303 |
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| subjects | Adult Asymptomatic Diseases Autoantibodies - blood Autoantibodies - immunology BNT162 Vaccine Brief Report ChAdOx1 nCoV-19 Clinical Trials and Observations COVID-19 - prevention & control COVID-19 Vaccines - adverse effects Female Free s Health Personnel Humans Immunoenzyme Techniques Immunoglobulin G - blood Immunoglobulin G - immunology Male Middle Aged Platelet Activation Platelet Factor 4 - immunology Polyelectrolytes Purpura, Thrombotic Thrombocytopenic - etiology Purpura, Thrombotic Thrombocytopenic - immunology Seroconversion Thrombocytopenia Thrombophilia - etiology Thrombosis and Hemostasis Vaccination - adverse effects |
| title | Frequency of positive anti-PF4/polyanion antibody tests after COVID-19 vaccination with ChAdOx1 nCoV-19 and BNT162b2 |
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