Imbalance between procoagulant factors and natural coagulation inhibitors contributes to hypercoagulability in the critically ill COVID-19 patient: clinical implications.
Identifieur interne : 000128 ( Main/Corpus ); précédent : 000127; suivant : 000129Imbalance between procoagulant factors and natural coagulation inhibitors contributes to hypercoagulability in the critically ill COVID-19 patient: clinical implications.
Auteurs : S. Voicu ; M. Delrue ; B G Chousterman ; A. Stépanian ; P. Bonnin ; I. Malissin ; N. Deye ; M. Neuwirth ; C. Ketfi ; A. Mebazaa ; V. Siguret ; B. MégarbaneSource :
- European review for medical and pharmacological sciences [ 2284-0729 ] ; 2020.
English descriptors
- KwdEn :
- Aged (MeSH), Area Under Curve (MeSH), Betacoronavirus (isolation & purification), Blood Coagulation Factor Inhibitors (metabolism), Blood Coagulation Factors (metabolism), Body Mass Index (MeSH), Coronavirus Infections (complications), Coronavirus Infections (diagnosis), Coronavirus Infections (virology), Critical Illness (MeSH), Factor V (analysis), Factor VIII (analysis), Female (MeSH), Fibrin Fibrinogen Degradation Products (analysis), Fibrinogen (analysis), Humans (MeSH), Male (MeSH), Middle Aged (MeSH), Pandemics (MeSH), Pneumonia, Viral (complications), Pneumonia, Viral (diagnosis), Pneumonia, Viral (virology), Protein C (analysis), Protein S (analysis), ROC Curve (MeSH), Venous Thromboembolism (complications), Venous Thromboembolism (diagnosis).
- MESH :
- chemical , analysis : Factor V, Factor VIII, Fibrin Fibrinogen Degradation Products, Fibrinogen, Protein C, Protein S.
- chemical , metabolism : Blood Coagulation Factor Inhibitors, Blood Coagulation Factors.
- complications : Coronavirus Infections, Pneumonia, Viral, Venous Thromboembolism.
- diagnosis : Coronavirus Infections, Pneumonia, Viral, Venous Thromboembolism.
- isolation & purification : Betacoronavirus.
- virology : Coronavirus Infections, Pneumonia, Viral.
- Aged, Area Under Curve, Body Mass Index, Critical Illness, Female, Humans, Male, Middle Aged, Pandemics, ROC Curve.
Abstract
OBJECTIVE
Coronavirus Disease-2019 (COVID-19) predisposes patients to thrombosis which underlying mechanisms are still incompletely understood. We sought to investigate the balance between procoagulant factors and natural coagulation inhibitors in the critically ill COVID-19 patient and to evaluate the usefulness of hemostasis parameters to identify patients at risk of venous thromboembolic event (VTE).
PATIENTS AND METHODS
We conducted an observational study recording VTEs defined as deep vein thrombosis or pulmonary embolism using lower limb ultrasound (92% of the patients), computed tomography pulmonary angiography (6%) and both tests (2%). We developed a comprehensive analysis of hemostasis.
RESULTS
Ninety-two consecutive mechanically ventilated COVID-19 patients (age, 62 years [53-69] (median [25th-75th percentiles]); M/F sex ratio, 2.5; body-mass index, 28 kg/m2 [25-32]; past hypertension (52%) and diabetes mellitus (30%)) admitted to the Intensive Care Unit (ICU) from 03/11/2020 to 5/05/2020, were included. When tested, patients were receiving prophylactic (74%) or therapeutic (26%) anticoagulation. Forty patients (43%) were diagnosed with VTE. Patients displayed inflammatory and prothrombotic profile including markedly elevated plasma fibrinogen (7.7 g/L [6.1-8.6]), D-dimer (3,360 ng/mL [1668-7575]), factor V (166 IU/dL [136-195]) and factor VIII activities (294 IU/dL [223-362]). We evidenced significant discrepant protein C anticoagulant and chromogenic activities, combined with slightly decreased protein S activity. Plasma D-dimer >3,300 ng/mL predicted VTE presence with 78% (95%-confidence interval (95% CI), 62-89) sensitivity, 69% (95% CI, 55-81) specificity, 66% (95% CI, 51-79) positive predictive value and 80% (95% CI, 65-90) negative predictive value [area under the ROC curve, 0.779 (95%CI, 0.681-0.859), p=0.0001].
CONCLUSIONS
Mechanically ventilated COVID-19 patients present with an imbalance between markedly increased factor V/VIII activity and overwhelmed protein C/S pathway. Plasma D-dimer may be a useful biomarker at the bedside for suspicion of VTE.
DOI: 10.26355/eurrev_202009_22866
PubMed: 32965009
Links to Exploration step
pubmed:32965009Le document en format XML
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Stépanian</name></author><author><name sortKey="Bonnin, P" sort="Bonnin, P" uniqKey="Bonnin P" first="P" last="Bonnin">P. Bonnin</name></author><author><name sortKey="Malissin, I" sort="Malissin, I" uniqKey="Malissin I" first="I" last="Malissin">I. Malissin</name></author><author><name sortKey="Deye, N" sort="Deye, N" uniqKey="Deye N" first="N" last="Deye">N. Deye</name></author><author><name sortKey="Neuwirth, M" sort="Neuwirth, M" uniqKey="Neuwirth M" first="M" last="Neuwirth">M. Neuwirth</name></author><author><name sortKey="Ketfi, C" sort="Ketfi, C" uniqKey="Ketfi C" first="C" last="Ketfi">C. Ketfi</name></author><author><name sortKey="Mebazaa, A" sort="Mebazaa, A" uniqKey="Mebazaa A" first="A" last="Mebazaa">A. Mebazaa</name></author><author><name sortKey="Siguret, V" sort="Siguret, V" uniqKey="Siguret V" first="V" last="Siguret">V. Siguret</name></author><author><name sortKey="Megarbane, B" sort="Megarbane, B" uniqKey="Megarbane B" first="B" last="Mégarbane">B. Mégarbane</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2020">2020</date><idno type="RBID">pubmed:32965009</idno><idno type="pmid">32965009</idno><idno type="doi">10.26355/eurrev_202009_22866</idno><idno type="wicri:Area/Main/Corpus">000128</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000128</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Imbalance between procoagulant factors and natural coagulation inhibitors contributes to hypercoagulability in the critically ill COVID-19 patient: clinical implications.</title><author><name sortKey="Voicu, S" sort="Voicu, S" uniqKey="Voicu S" first="S" last="Voicu">S. Voicu</name><affiliation><nlm:affiliation>Department of Medical and Toxicological Critical Care, Lariboisière Hospital, Université de Paris, Paris, France. bruno.megarbane@lrb.aphp.fr.</nlm:affiliation></affiliation></author><author><name sortKey="Delrue, M" sort="Delrue, M" uniqKey="Delrue M" first="M" last="Delrue">M. Delrue</name></author><author><name sortKey="Chousterman, B G" sort="Chousterman, B G" uniqKey="Chousterman B" first="B G" last="Chousterman">B G Chousterman</name></author><author><name sortKey="Stepanian, A" sort="Stepanian, A" uniqKey="Stepanian A" first="A" last="Stépanian">A. Stépanian</name></author><author><name sortKey="Bonnin, P" sort="Bonnin, P" uniqKey="Bonnin P" first="P" last="Bonnin">P. Bonnin</name></author><author><name sortKey="Malissin, I" sort="Malissin, I" uniqKey="Malissin I" first="I" last="Malissin">I. Malissin</name></author><author><name sortKey="Deye, N" sort="Deye, N" uniqKey="Deye N" first="N" last="Deye">N. Deye</name></author><author><name sortKey="Neuwirth, M" sort="Neuwirth, M" uniqKey="Neuwirth M" first="M" last="Neuwirth">M. Neuwirth</name></author><author><name sortKey="Ketfi, C" sort="Ketfi, C" uniqKey="Ketfi C" first="C" last="Ketfi">C. Ketfi</name></author><author><name sortKey="Mebazaa, A" sort="Mebazaa, A" uniqKey="Mebazaa A" first="A" last="Mebazaa">A. Mebazaa</name></author><author><name sortKey="Siguret, V" sort="Siguret, V" uniqKey="Siguret V" first="V" last="Siguret">V. Siguret</name></author><author><name sortKey="Megarbane, B" sort="Megarbane, B" uniqKey="Megarbane B" first="B" last="Mégarbane">B. Mégarbane</name></author></analytic><series><title level="j">European review for medical and pharmacological sciences</title><idno type="eISSN">2284-0729</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Aged (MeSH)</term><term>Area Under Curve (MeSH)</term><term>Betacoronavirus (isolation & purification)</term><term>Blood Coagulation Factor Inhibitors (metabolism)</term><term>Blood Coagulation Factors (metabolism)</term><term>Body Mass Index (MeSH)</term><term>Coronavirus Infections (complications)</term><term>Coronavirus Infections (diagnosis)</term><term>Coronavirus Infections (virology)</term><term>Critical Illness (MeSH)</term><term>Factor V (analysis)</term><term>Factor VIII (analysis)</term><term>Female (MeSH)</term><term>Fibrin Fibrinogen Degradation Products (analysis)</term><term>Fibrinogen (analysis)</term><term>Humans (MeSH)</term><term>Male (MeSH)</term><term>Middle Aged (MeSH)</term><term>Pandemics (MeSH)</term><term>Pneumonia, Viral (complications)</term><term>Pneumonia, Viral (diagnosis)</term><term>Pneumonia, Viral (virology)</term><term>Protein C (analysis)</term><term>Protein S (analysis)</term><term>ROC Curve (MeSH)</term><term>Venous Thromboembolism (complications)</term><term>Venous Thromboembolism (diagnosis)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analysis" xml:lang="en"><term>Factor V</term><term>Factor VIII</term><term>Fibrin Fibrinogen Degradation Products</term><term>Fibrinogen</term><term>Protein C</term><term>Protein S</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Blood Coagulation Factor Inhibitors</term><term>Blood Coagulation Factors</term></keywords><keywords scheme="MESH" qualifier="complications" xml:lang="en"><term>Coronavirus Infections</term><term>Pneumonia, Viral</term><term>Venous Thromboembolism</term></keywords><keywords scheme="MESH" qualifier="diagnosis" xml:lang="en"><term>Coronavirus Infections</term><term>Pneumonia, Viral</term><term>Venous Thromboembolism</term></keywords><keywords scheme="MESH" qualifier="isolation & purification" xml:lang="en"><term>Betacoronavirus</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Coronavirus Infections</term><term>Pneumonia, Viral</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Aged</term><term>Area Under Curve</term><term>Body Mass Index</term><term>Critical Illness</term><term>Female</term><term>Humans</term><term>Male</term><term>Middle Aged</term><term>Pandemics</term><term>ROC Curve</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p><b>OBJECTIVE</b></p><p>Coronavirus Disease-2019 (COVID-19) predisposes patients to thrombosis which underlying mechanisms are still incompletely understood. We sought to investigate the balance between procoagulant factors and natural coagulation inhibitors in the critically ill COVID-19 patient and to evaluate the usefulness of hemostasis parameters to identify patients at risk of venous thromboembolic event (VTE).</p></div><div type="abstract" xml:lang="en"><p><b>PATIENTS AND METHODS</b></p><p>We conducted an observational study recording VTEs defined as deep vein thrombosis or pulmonary embolism using lower limb ultrasound (92% of the patients), computed tomography pulmonary angiography (6%) and both tests (2%). We developed a comprehensive analysis of hemostasis.</p></div><div type="abstract" xml:lang="en"><p><b>RESULTS</b></p><p>Ninety-two consecutive mechanically ventilated COVID-19 patients (age, 62 years [53-69] (median [25th-75th percentiles]); M/F sex ratio, 2.5; body-mass index, 28 kg/m2 [25-32]; past hypertension (52%) and diabetes mellitus (30%)) admitted to the Intensive Care Unit (ICU) from 03/11/2020 to 5/05/2020, were included. When tested, patients were receiving prophylactic (74%) or therapeutic (26%) anticoagulation. Forty patients (43%) were diagnosed with VTE. Patients displayed inflammatory and prothrombotic profile including markedly elevated plasma fibrinogen (7.7 g/L [6.1-8.6]), D-dimer (3,360 ng/mL [1668-7575]), factor V (166 IU/dL [136-195]) and factor VIII activities (294 IU/dL [223-362]). We evidenced significant discrepant protein C anticoagulant and chromogenic activities, combined with slightly decreased protein S activity. Plasma D-dimer >3,300 ng/mL predicted VTE presence with 78% (95%-confidence interval (95% CI), 62-89) sensitivity, 69% (95% CI, 55-81) specificity, 66% (95% CI, 51-79) positive predictive value and 80% (95% CI, 65-90) negative predictive value [area under the ROC curve, 0.779 (95%CI, 0.681-0.859), p=0.0001].</p></div><div type="abstract" xml:lang="en"><p><b>CONCLUSIONS</b></p><p>Mechanically ventilated COVID-19 patients present with an imbalance between markedly increased factor V/VIII activity and overwhelmed protein C/S pathway. Plasma D-dimer may be a useful biomarker at the bedside for suspicion of VTE.</p></div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">32965009</PMID><DateCompleted><Year>2020</Year><Month>09</Month><Day>30</Day></DateCompleted><DateRevised><Year>2020</Year><Month>09</Month><Day>30</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Electronic">2284-0729</ISSN><JournalIssue CitedMedium="Internet"><Volume>24</Volume><Issue>17</Issue><PubDate><Year>2020</Year><Month>Sep</Month></PubDate></JournalIssue><Title>European review for medical and pharmacological sciences</Title><ISOAbbreviation>Eur Rev Med Pharmacol Sci</ISOAbbreviation></Journal><ArticleTitle>Imbalance between procoagulant factors and natural coagulation inhibitors contributes to hypercoagulability in the critically ill COVID-19 patient: clinical implications.</ArticleTitle><Pagination><MedlinePgn>9161-9168</MedlinePgn></Pagination><ELocationID EIdType="pii" ValidYN="Y">22866</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.26355/eurrev_202009_22866</ELocationID><Abstract><AbstractText Label="OBJECTIVE" NlmCategory="OBJECTIVE">Coronavirus Disease-2019 (COVID-19) predisposes patients to thrombosis which underlying mechanisms are still incompletely understood. We sought to investigate the balance between procoagulant factors and natural coagulation inhibitors in the critically ill COVID-19 patient and to evaluate the usefulness of hemostasis parameters to identify patients at risk of venous thromboembolic event (VTE).</AbstractText><AbstractText Label="PATIENTS AND METHODS" NlmCategory="METHODS">We conducted an observational study recording VTEs defined as deep vein thrombosis or pulmonary embolism using lower limb ultrasound (92% of the patients), computed tomography pulmonary angiography (6%) and both tests (2%). We developed a comprehensive analysis of hemostasis.</AbstractText><AbstractText Label="RESULTS" NlmCategory="RESULTS">Ninety-two consecutive mechanically ventilated COVID-19 patients (age, 62 years [53-69] (median [25th-75th percentiles]); M/F sex ratio, 2.5; body-mass index, 28 kg/m2 [25-32]; past hypertension (52%) and diabetes mellitus (30%)) admitted to the Intensive Care Unit (ICU) from 03/11/2020 to 5/05/2020, were included. When tested, patients were receiving prophylactic (74%) or therapeutic (26%) anticoagulation. Forty patients (43%) were diagnosed with VTE. Patients displayed inflammatory and prothrombotic profile including markedly elevated plasma fibrinogen (7.7 g/L [6.1-8.6]), D-dimer (3,360 ng/mL [1668-7575]), factor V (166 IU/dL [136-195]) and factor VIII activities (294 IU/dL [223-362]). We evidenced significant discrepant protein C anticoagulant and chromogenic activities, combined with slightly decreased protein S activity. Plasma D-dimer >3,300 ng/mL predicted VTE presence with 78% (95%-confidence interval (95% CI), 62-89) sensitivity, 69% (95% CI, 55-81) specificity, 66% (95% CI, 51-79) positive predictive value and 80% (95% CI, 65-90) negative predictive value [area under the ROC curve, 0.779 (95%CI, 0.681-0.859), p=0.0001].</AbstractText><AbstractText Label="CONCLUSIONS" NlmCategory="CONCLUSIONS">Mechanically ventilated COVID-19 patients present with an imbalance between markedly increased factor V/VIII activity and overwhelmed protein C/S pathway. Plasma D-dimer may be a useful biomarker at the bedside for suspicion of VTE.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Voicu</LastName><ForeName>S</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Medical and Toxicological Critical Care, Lariboisière Hospital, Université de Paris, Paris, France. bruno.megarbane@lrb.aphp.fr.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Delrue</LastName><ForeName>M</ForeName><Initials>M</Initials></Author><Author ValidYN="Y"><LastName>Chousterman</LastName><ForeName>B G</ForeName><Initials>BG</Initials></Author><Author ValidYN="Y"><LastName>Stépanian</LastName><ForeName>A</ForeName><Initials>A</Initials></Author><Author ValidYN="Y"><LastName>Bonnin</LastName><ForeName>P</ForeName><Initials>P</Initials></Author><Author ValidYN="Y"><LastName>Malissin</LastName><ForeName>I</ForeName><Initials>I</Initials></Author><Author ValidYN="Y"><LastName>Deye</LastName><ForeName>N</ForeName><Initials>N</Initials></Author><Author ValidYN="Y"><LastName>Neuwirth</LastName><ForeName>M</ForeName><Initials>M</Initials></Author><Author ValidYN="Y"><LastName>Ketfi</LastName><ForeName>C</ForeName><Initials>C</Initials></Author><Author ValidYN="Y"><LastName>Mebazaa</LastName><ForeName>A</ForeName><Initials>A</Initials></Author><Author ValidYN="Y"><LastName>Siguret</LastName><ForeName>V</ForeName><Initials>V</Initials></Author><Author ValidYN="Y"><LastName>Mégarbane</LastName><ForeName>B</ForeName><Initials>B</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>Italy</Country><MedlineTA>Eur Rev Med Pharmacol Sci</MedlineTA><NlmUniqueID>9717360</NlmUniqueID><ISSNLinking>1128-3602</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D019774">Blood Coagulation Factor Inhibitors</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D001779">Blood Coagulation Factors</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D005338">Fibrin Fibrinogen Degradation Products</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D011486">Protein C</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D017293">Protein S</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C036309">fibrin fragment D</NameOfSubstance></Chemical><Chemical><RegistryNumber>9001-24-5</RegistryNumber><NameOfSubstance UI="D005165">Factor V</NameOfSubstance></Chemical><Chemical><RegistryNumber>9001-27-8</RegistryNumber><NameOfSubstance UI="D005169">Factor VIII</NameOfSubstance></Chemical><Chemical><RegistryNumber>9001-32-5</RegistryNumber><NameOfSubstance UI="D005340">Fibrinogen</NameOfSubstance></Chemical></ChemicalList><SupplMeshList><SupplMeshName Type="Disease" UI="C000657245">COVID-19</SupplMeshName><SupplMeshName Type="Organism" UI="C000656484">severe acute respiratory syndrome coronavirus 2</SupplMeshName></SupplMeshList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000368" MajorTopicYN="N">Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D019540" MajorTopicYN="N">Area Under Curve</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000073640" MajorTopicYN="N">Betacoronavirus</DescriptorName><QualifierName UI="Q000302" MajorTopicYN="N">isolation & purification</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D019774" MajorTopicYN="N">Blood Coagulation Factor Inhibitors</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001779" MajorTopicYN="N">Blood Coagulation Factors</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D015992" MajorTopicYN="N">Body Mass Index</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D018352" MajorTopicYN="N">Coronavirus Infections</DescriptorName><QualifierName UI="Q000150" MajorTopicYN="N">complications</QualifierName><QualifierName UI="Q000175" MajorTopicYN="Y">diagnosis</QualifierName><QualifierName UI="Q000821" MajorTopicYN="N">virology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D016638" MajorTopicYN="N">Critical Illness</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005165" MajorTopicYN="N">Factor V</DescriptorName><QualifierName UI="Q000032" MajorTopicYN="N">analysis</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005169" MajorTopicYN="N">Factor VIII</DescriptorName><QualifierName UI="Q000032" MajorTopicYN="N">analysis</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005338" MajorTopicYN="N">Fibrin Fibrinogen Degradation Products</DescriptorName><QualifierName UI="Q000032" MajorTopicYN="N">analysis</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005340" MajorTopicYN="N">Fibrinogen</DescriptorName><QualifierName UI="Q000032" MajorTopicYN="N">analysis</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008875" MajorTopicYN="N">Middle Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D058873" MajorTopicYN="N">Pandemics</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011024" MajorTopicYN="N">Pneumonia, Viral</DescriptorName><QualifierName UI="Q000150" MajorTopicYN="N">complications</QualifierName><QualifierName UI="Q000175" MajorTopicYN="Y">diagnosis</QualifierName><QualifierName UI="Q000821" MajorTopicYN="N">virology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D011486" MajorTopicYN="N">Protein C</DescriptorName><QualifierName UI="Q000032" MajorTopicYN="N">analysis</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D017293" MajorTopicYN="N">Protein S</DescriptorName><QualifierName UI="Q000032" MajorTopicYN="N">analysis</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D012372" MajorTopicYN="N">ROC Curve</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D054556" MajorTopicYN="N">Venous Thromboembolism</DescriptorName><QualifierName UI="Q000150" MajorTopicYN="N">complications</QualifierName><QualifierName UI="Q000175" MajorTopicYN="N">diagnosis</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2020</Year><Month>9</Month><Day>23</Day><Hour>9</Hour><Minute>3</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2020</Year><Month>9</Month><Day>24</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2020</Year><Month>10</Month><Day>2</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">32965009</ArticleId><ArticleId IdType="doi">10.26355/eurrev_202009_22866</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
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