Thrombotic events following tocilizumab therapy in critically ill COVID-19 patients: a Façade for prognostic markers.
Identifieur interne : 000364 ( Main/Exploration ); précédent : 000363; suivant : 000365Thrombotic events following tocilizumab therapy in critically ill COVID-19 patients: a Façade for prognostic markers.
Auteurs : Bassam Atallah [Émirats arabes unis, États-Unis] ; Wasim El Nekidy [Émirats arabes unis, États-Unis] ; Saad I. Mallah [Bahreïn] ; Antoine Cherfan [Émirats arabes unis] ; Laila Abdelwareth [Émirats arabes unis] ; Jihad Mallat [États-Unis, Émirats arabes unis, France] ; Fadi Hamed [Émirats arabes unis]Source :
- Thrombosis journal [ 1477-9560 ] ; 2020.
Abstract
Background
Hospitals in the Middle East Gulf region have experienced an influx of COVID-19 patients to their medical wards and intensive care units. The hypercoagulability of these patients has been widely reported on a global scale. However, many of the experimental treatments used to manage the various complications of COVID-19 have not been widely studied in this context. The effect of the current treatment protocols on patients' diagnostic and prognostic biomarkers may thus impact the validity of the algorithms adopted.
Case presentation
In this case series, we report four cases of venous thromboembolism and 1 case of arterial thrombotic event, in patients treated with standard or intensified prophylactic doses of unfractionated heparin or low molecular weight heparin at our institution. Tocilizumab has been utilized as an add-on therapy to the standard of care to treat patients with SARS-CoV-2 associated acute respiratory distress syndrome, in order to dampen the hyperinflammatory response. It is imperative to be aware that this drug may be masking the inflammatory markers (e.g. IL6, CRP, fibrinogen, and ferritin), without reducing the risk of thrombotic events in this population, creating instead a façade of an improved prognostic outcome. However, the D-dimer levels remained prognostically reliable in these cases, as they were not affected by the drug and continued to be at the highest level until event occurrence.
Conclusions
In the setting of tocilizumab therapy, traditional prognostic markers of worsening infection and inflammation, and thus potential risk of acute thrombosis, should be weighed carefully as they may not be reliable for prognosis and may create a façade of an improved prognostic outcome insteasd. Additionally, the fact that thrombotic events continued to be observed despite decrease in inflammatory markers and the proactive anticoagulative approach adopted, raises more questions about the coagulative mechanisms at play in COVID-19, and the appropriate management strategy.
DOI: 10.1186/s12959-020-00236-9
PubMed: 32922212
PubMed Central: PMC7479301
Affiliations:
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type="state">Ohio</region></placeName><wicri:cityArea>Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland</wicri:cityArea></affiliation></author><author><name sortKey="El Nekidy, Wasim" sort="El Nekidy, Wasim" uniqKey="El Nekidy W" first="Wasim" last="El Nekidy">Wasim El Nekidy</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pharmacy Services, Cleveland Clinic Abu Dhabi, Al Maryah Island, Abu Dhabi, United Arab Emirates.</nlm:affiliation><country xml:lang="fr">Émirats arabes unis</country><wicri:regionArea>Department of Pharmacy Services, Cleveland Clinic Abu Dhabi, Al Maryah Island, Abu Dhabi</wicri:regionArea><wicri:noRegion>Abu Dhabi</wicri:noRegion></affiliation><affiliation wicri:level="2"><nlm:affiliation>Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH USA.</nlm:affiliation><country>États-Unis</country><placeName><region 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Mallah</name><affiliation wicri:level="1"><nlm:affiliation>School of Medicine, Royal College of Surgeons in Ireland-Bahrain, Al Sayh, Bahrain.</nlm:affiliation><country xml:lang="fr">Bahreïn</country><wicri:regionArea>School of Medicine, Royal College of Surgeons in Ireland-Bahrain, Al Sayh</wicri:regionArea><wicri:noRegion>Al Sayh</wicri:noRegion></affiliation></author><author><name sortKey="Cherfan, Antoine" sort="Cherfan, Antoine" uniqKey="Cherfan A" first="Antoine" last="Cherfan">Antoine Cherfan</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pharmacy Services, Cleveland Clinic Abu Dhabi, Al Maryah Island, Abu Dhabi, United Arab Emirates.</nlm:affiliation><country xml:lang="fr">Émirats arabes unis</country><wicri:regionArea>Department of Pharmacy Services, Cleveland Clinic Abu Dhabi, Al Maryah Island, Abu Dhabi</wicri:regionArea><wicri:noRegion>Abu Dhabi</wicri:noRegion></affiliation></author><author><name sortKey="Abdelwareth, Laila" sort="Abdelwareth, Laila" uniqKey="Abdelwareth L" first="Laila" last="Abdelwareth">Laila Abdelwareth</name><affiliation wicri:level="1"><nlm:affiliation>Department of Clinical Pathology, Cleveland Clinic Abu Dhabi, Al Maryah Island, Abu Dhabi, United Arab Emirates.</nlm:affiliation><country xml:lang="fr">Émirats arabes unis</country><wicri:regionArea>Department of Clinical Pathology, Cleveland Clinic Abu Dhabi, Al Maryah Island, Abu Dhabi</wicri:regionArea><wicri:noRegion>Abu Dhabi</wicri:noRegion></affiliation></author><author><name sortKey="Mallat, Jihad" sort="Mallat, Jihad" uniqKey="Mallat J" first="Jihad" last="Mallat">Jihad Mallat</name><affiliation wicri:level="2"><nlm:affiliation>Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH USA.</nlm:affiliation><country>États-Unis</country><placeName><region type="state">Ohio</region></placeName><wicri:cityArea>Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland</wicri:cityArea></affiliation><affiliation wicri:level="1"><nlm:affiliation>Critical Care Institute, Cleveland Clinic Abu Dhabi, Al Maryah Island, Abu Dhabi, United Arab Emirates.</nlm:affiliation><country xml:lang="fr">Émirats arabes unis</country><wicri:regionArea>Critical Care Institute, Cleveland Clinic Abu Dhabi, Al Maryah Island, Abu Dhabi</wicri:regionArea><wicri:noRegion>Abu Dhabi</wicri:noRegion></affiliation><affiliation wicri:level="3"><nlm:affiliation>Normandy University, UNICAEN ED 497, Caen, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Normandy University, UNICAEN ED 497, Caen</wicri:regionArea><placeName><region type="region">Région Normandie</region><region type="old region">Basse-Normandie</region><settlement type="city">Caen</settlement></placeName></affiliation></author><author><name sortKey="Hamed, Fadi" sort="Hamed, Fadi" uniqKey="Hamed F" first="Fadi" last="Hamed">Fadi Hamed</name><affiliation wicri:level="1"><nlm:affiliation>Critical Care Institute, Cleveland Clinic Abu Dhabi, Al Maryah Island, Abu Dhabi, United Arab Emirates.</nlm:affiliation><country xml:lang="fr">Émirats arabes unis</country><wicri:regionArea>Critical Care Institute, Cleveland Clinic Abu Dhabi, Al Maryah Island, Abu Dhabi</wicri:regionArea><wicri:noRegion>Abu Dhabi</wicri:noRegion></affiliation></author></analytic><series><title level="j">Thrombosis journal</title><idno type="ISSN">1477-9560</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p><b>Background</b></p><p>Hospitals in the Middle East Gulf region have experienced an influx of COVID-19 patients to their medical wards and intensive care units. The hypercoagulability of these patients has been widely reported on a global scale. However, many of the experimental treatments used to manage the various complications of COVID-19 have not been widely studied in this context. The effect of the current treatment protocols on patients' diagnostic and prognostic biomarkers may thus impact the validity of the algorithms adopted.</p></div><div type="abstract" xml:lang="en"><p><b>Case presentation</b></p><p>In this case series, we report four cases of venous thromboembolism and 1 case of arterial thrombotic event, in patients treated with standard or intensified prophylactic doses of unfractionated heparin or low molecular weight heparin at our institution. Tocilizumab has been utilized as an add-on therapy to the standard of care to treat patients with SARS-CoV-2 associated acute respiratory distress syndrome, in order to dampen the hyperinflammatory response. It is imperative to be aware that this drug may be masking the inflammatory markers (e.g. IL6, CRP, fibrinogen, and ferritin), without reducing the risk of thrombotic events in this population, creating instead a façade of an improved prognostic outcome. However, the D-dimer levels remained prognostically reliable in these cases, as they were not affected by the drug and continued to be at the highest level until event occurrence.</p></div><div type="abstract" xml:lang="en"><p><b>Conclusions</b></p><p>In the setting of tocilizumab therapy, traditional prognostic markers of worsening infection and inflammation, and thus potential risk of acute thrombosis, should be weighed carefully as they may not be reliable for prognosis and may create a façade of an improved prognostic outcome insteasd. Additionally, the fact that thrombotic events continued to be observed despite decrease in inflammatory markers and the proactive anticoagulative approach adopted, raises more questions about the coagulative mechanisms at play in COVID-19, and the appropriate management strategy.</p></div></front></TEI><pubmed><MedlineCitation Status="PubMed-not-MEDLINE" Owner="NLM"><PMID Version="1">32922212</PMID><DateRevised><Year>2020</Year><Month>09</Month><Day>16</Day></DateRevised><Article PubModel="Electronic-eCollection"><Journal><ISSN IssnType="Print">1477-9560</ISSN><JournalIssue CitedMedium="Print"><Volume>18</Volume><PubDate><Year>2020</Year></PubDate></JournalIssue><Title>Thrombosis journal</Title><ISOAbbreviation>Thromb J</ISOAbbreviation></Journal><ArticleTitle>Thrombotic events following tocilizumab therapy in critically ill COVID-19 patients: a Façade for prognostic markers.</ArticleTitle><Pagination><MedlinePgn>22</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1186/s12959-020-00236-9</ELocationID><Abstract><AbstractText Label="Background" NlmCategory="UNASSIGNED">Hospitals in the Middle East Gulf region have experienced an influx of COVID-19 patients to their medical wards and intensive care units. The hypercoagulability of these patients has been widely reported on a global scale. However, many of the experimental treatments used to manage the various complications of COVID-19 have not been widely studied in this context. The effect of the current treatment protocols on patients' diagnostic and prognostic biomarkers may thus impact the validity of the algorithms adopted.</AbstractText><AbstractText Label="Case presentation" NlmCategory="UNASSIGNED">In this case series, we report four cases of venous thromboembolism and 1 case of arterial thrombotic event, in patients treated with standard or intensified prophylactic doses of unfractionated heparin or low molecular weight heparin at our institution. Tocilizumab has been utilized as an add-on therapy to the standard of care to treat patients with SARS-CoV-2 associated acute respiratory distress syndrome, in order to dampen the hyperinflammatory response. It is imperative to be aware that this drug may be masking the inflammatory markers (e.g. IL6, CRP, fibrinogen, and ferritin), without reducing the risk of thrombotic events in this population, creating instead a façade of an improved prognostic outcome. However, the D-dimer levels remained prognostically reliable in these cases, as they were not affected by the drug and continued to be at the highest level until event occurrence.</AbstractText><AbstractText Label="Conclusions" NlmCategory="UNASSIGNED">In the setting of tocilizumab therapy, traditional prognostic markers of worsening infection and inflammation, and thus potential risk of acute thrombosis, should be weighed carefully as they may not be reliable for prognosis and may create a façade of an improved prognostic outcome insteasd. Additionally, the fact that thrombotic events continued to be observed despite decrease in inflammatory markers and the proactive anticoagulative approach adopted, raises more questions about the coagulative mechanisms at play in COVID-19, and the appropriate management strategy.</AbstractText><CopyrightInformation>© The Author(s) 2020.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Atallah</LastName><ForeName>Bassam</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Department of Pharmacy Services, Cleveland Clinic Abu Dhabi, Al Maryah Island, Abu Dhabi, United Arab Emirates.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH USA.</Affiliation><Identifier Source="GRID">grid.254293.b</Identifier><Identifier Source="ISNI">0000 0004 0435 0569</Identifier></AffiliationInfo></Author><Author ValidYN="Y"><LastName>El Nekidy</LastName><ForeName>Wasim</ForeName><Initials>W</Initials><AffiliationInfo><Affiliation>Department of Pharmacy Services, Cleveland Clinic Abu Dhabi, Al Maryah Island, Abu Dhabi, United Arab Emirates.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH USA.</Affiliation><Identifier Source="GRID">grid.254293.b</Identifier><Identifier Source="ISNI">0000 0004 0435 0569</Identifier></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mallah</LastName><ForeName>Saad I</ForeName><Initials>SI</Initials><AffiliationInfo><Affiliation>School of Medicine, Royal College of Surgeons in Ireland-Bahrain, Al Sayh, Bahrain.</Affiliation><Identifier Source="GRID">grid.459866.0</Identifier><Identifier Source="ISNI">0000 0004 0398 3129</Identifier></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cherfan</LastName><ForeName>Antoine</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Department of Pharmacy Services, Cleveland Clinic Abu Dhabi, Al Maryah Island, Abu Dhabi, United Arab Emirates.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>AbdelWareth</LastName><ForeName>Laila</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Department of Clinical Pathology, Cleveland Clinic Abu Dhabi, Al Maryah Island, Abu Dhabi, United Arab Emirates.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mallat</LastName><ForeName>Jihad</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH USA.</Affiliation><Identifier Source="GRID">grid.254293.b</Identifier><Identifier Source="ISNI">0000 0004 0435 0569</Identifier></AffiliationInfo><AffiliationInfo><Affiliation>Critical Care Institute, Cleveland Clinic Abu Dhabi, Al Maryah Island, Abu Dhabi, United Arab Emirates.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Normandy University, UNICAEN ED 497, Caen, France.</Affiliation><Identifier Source="GRID">grid.460771.3</Identifier><Identifier Source="ISNI">0000 0004 1785 9671</Identifier></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hamed</LastName><ForeName>Fadi</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Critical Care Institute, Cleveland Clinic Abu Dhabi, Al Maryah Island, Abu Dhabi, United Arab Emirates.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D002363">Case Reports</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2020</Year><Month>09</Month><Day>09</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Thromb J</MedlineTA><NlmUniqueID>101170542</NlmUniqueID><ISSNLinking>1477-9560</ISSNLinking></MedlineJournalInfo><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">COVID-19</Keyword><Keyword MajorTopicYN="N">D-dimers</Keyword><Keyword MajorTopicYN="N">Prognostic markers</Keyword><Keyword MajorTopicYN="N">Thrombosis</Keyword><Keyword MajorTopicYN="N">Tocilizumab</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2020</Year><Month>06</Month><Day>30</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2020</Year><Month>08</Month><Day>26</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2020</Year><Month>9</Month><Day>14</Day><Hour>5</Hour><Minute>49</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2020</Year><Month>9</Month><Day>15</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate 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<ReferenceList><Reference><Citation>Arthritis Res Ther. 2013;15(6):R204</Citation><ArticleIdList><ArticleId IdType="pubmed">24295403</ArticleId></ArticleIdList></Reference><Reference><Citation>N Engl J Med. 2020 Jul 16;383(3):288-290</Citation><ArticleIdList><ArticleId IdType="pubmed">32369280</ArticleId></ArticleIdList></Reference><Reference><Citation>Lancet. 2020 May 2;395(10234):1417-1418</Citation><ArticleIdList><ArticleId IdType="pubmed">32325026</ArticleId></ArticleIdList></Reference><Reference><Citation>Eur Heart J Cardiovasc Pharmacother. 2020 Jul 1;6(4):260-261</Citation><ArticleIdList><ArticleId IdType="pubmed">32352517</ArticleId></ArticleIdList></Reference><Reference><Citation>Expert Rev Clin Immunol. 2019 Aug;15(8):813-822</Citation><ArticleIdList><ArticleId IdType="pubmed">31219357</ArticleId></ArticleIdList></Reference><Reference><Citation>J Thromb Haemost. 2020 Jul 3;:</Citation><ArticleIdList><ArticleId IdType="pubmed">32619328</ArticleId></ArticleIdList></Reference><Reference><Citation>Lancet Rheumatol. 2020 Aug;2(8):e474-e484</Citation><ArticleIdList><ArticleId IdType="pubmed">32835257</ArticleId></ArticleIdList></Reference><Reference><Citation>Mod Rheumatol. 2018 Nov;28(6):976-980</Citation><ArticleIdList><ArticleId IdType="pubmed">29325462</ArticleId></ArticleIdList></Reference><Reference><Citation>Intensive Care Med. 2020 Jun;46(6):1089-1098</Citation><ArticleIdList><ArticleId IdType="pubmed">32367170</ArticleId></ArticleIdList></Reference><Reference><Citation>Br J Haematol. 2020 Jun;189(6):1050-1052</Citation><ArticleIdList><ArticleId IdType="pubmed">32304581</ArticleId></ArticleIdList></Reference><Reference><Citation>Chest. 2020 Jun 15;:</Citation><ArticleIdList><ArticleId IdType="pubmed">32553536</ArticleId></ArticleIdList></Reference><Reference><Citation>N Engl J Med. 2020 Jul 9;383(2):120-128</Citation><ArticleIdList><ArticleId IdType="pubmed">32437596</ArticleId></ArticleIdList></Reference><Reference><Citation>J Med Virol. 2020 Jul;92(7):814-818</Citation><ArticleIdList><ArticleId IdType="pubmed">32253759</ArticleId></ArticleIdList></Reference><Reference><Citation>Thromb Haemost. 2020 Jul 17;:</Citation><ArticleIdList><ArticleId IdType="pubmed">32679593</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></pubmed><affiliations><list><country><li>Bahreïn</li><li>France</li><li>Émirats arabes unis</li><li>États-Unis</li></country><region><li>Basse-Normandie</li><li>Ohio</li><li>Région Normandie</li></region><settlement><li>Caen</li></settlement></list><tree><country name="Émirats arabes unis"><noRegion><name sortKey="Atallah, Bassam" sort="Atallah, Bassam" uniqKey="Atallah B" first="Bassam" last="Atallah">Bassam Atallah</name></noRegion><name sortKey="Abdelwareth, Laila" sort="Abdelwareth, Laila" uniqKey="Abdelwareth L" first="Laila" last="Abdelwareth">Laila Abdelwareth</name><name sortKey="Cherfan, Antoine" sort="Cherfan, Antoine" uniqKey="Cherfan A" first="Antoine" last="Cherfan">Antoine Cherfan</name><name sortKey="El Nekidy, Wasim" sort="El Nekidy, Wasim" uniqKey="El Nekidy W" first="Wasim" last="El Nekidy">Wasim El Nekidy</name><name sortKey="Hamed, Fadi" sort="Hamed, Fadi" uniqKey="Hamed F" first="Fadi" last="Hamed">Fadi Hamed</name><name sortKey="Mallat, Jihad" sort="Mallat, Jihad" uniqKey="Mallat J" first="Jihad" last="Mallat">Jihad Mallat</name></country><country name="États-Unis"><region name="Ohio"><name sortKey="Atallah, Bassam" sort="Atallah, Bassam" uniqKey="Atallah B" first="Bassam" last="Atallah">Bassam Atallah</name></region><name sortKey="El Nekidy, Wasim" sort="El Nekidy, Wasim" uniqKey="El Nekidy W" first="Wasim" last="El Nekidy">Wasim El Nekidy</name><name sortKey="Mallat, Jihad" sort="Mallat, Jihad" uniqKey="Mallat J" first="Jihad" last="Mallat">Jihad Mallat</name></country><country name="Bahreïn"><noRegion><name sortKey="Mallah, Saad I" sort="Mallah, Saad I" uniqKey="Mallah S" first="Saad I" last="Mallah">Saad I. Mallah</name></noRegion></country><country name="France"><region name="Région Normandie"><name sortKey="Mallat, Jihad" sort="Mallat, Jihad" uniqKey="Mallat J" first="Jihad" last="Mallat">Jihad Mallat</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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