{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T14:37:53Z","timestamp":1776868673929,"version":"3.51.2"},"reference-count":43,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,3,3]],"date-time":"2022-03-03T00:00:00Z","timestamp":1646265600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Thrombosis is frequent during COVID-19 disease, and thus, identifying predictive factors of hemostasis associated with a poor prognosis is of interest. The objective was to explore coagulation disorders as early predictors of worsening critical conditions in the intensive care unit (ICU) using routine and more advanced explorations. Materials: Blood samples within 24 h of ICU admission for viscoelastic point-of-care testing, (VET), advanced laboratory tests: absolute immature platelet count (A-IPC), von Willebrand-GPIb activity (vWF-GpIb), prothrombin fragments 1 + 2 (F1 + 2), and the thrombin generation assay (TGA) were used. An association with worse outcomes was explored using univariable and multivariable analyses. Worsening was defined as death or the need for organ support. Results: An amount of 85 patients with 33 in critical condition were included. A-IPC were lower in worsening patients (9.6 [6.4\u201312.5] vs. 12.3 [8.3\u201320.7], p = 0.02) while fibrinogen (6.9 [6.1\u20137.7] vs. 6.2 [5.4\u20136.9], p = 0.03), vWF-GpIb (286 [265\u2013389] vs. 268 [216\u2013326], p = 0.03) and F1 + 2 (226 [151\u2013578] vs. 155 [129\u2013248], p = 0.01) were higher. There was no difference observed for D-dimer, TGA or VET. SAPS-II and A-IPC were independently associated with worsening (OR = 1.11 [1.06\u20131.17] and OR = 0.47 [0.25\u20130.76] respectively). The association of a SAPS-II \u2265 33 and an A-IPC \u2264 12.6 G\/L predicted the worsening of patients (sensitivity 58%, specificity 89%). Conclusions: Immature platelets are early predictors of worsening in severe COVID-19 patients, suggesting a key role of thrombopoiesis in the adaption of an organism to SARS-CoV-2 infection.<\/jats:p>","DOI":"10.3390\/jcm11051383","type":"journal-article","created":{"date-parts":[[2022,3,3]],"date-time":"2022-03-03T09:24:53Z","timestamp":1646299493000},"page":"1383","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Routine and Advanced Laboratory Tests for Hemostasis Disorders in COVID-19 Patients: A Prospective Cohort Study"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5632-7713","authenticated-orcid":false,"given":"Paul","family":"Billoir","sequence":"first","affiliation":[{"name":"Vascular Hemostasis Unit, CHU Rouen, Normandie University, UNIROUEN, INSERM U1096, F-76000 Rouen, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Perrine","family":"Lepr\u00eatre","sequence":"additional","affiliation":[{"name":"Medical Intensive Care Unit, CHU Rouen, Normandie University, UNIROUEN, INSERM U1096, F-76000 Rouen, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline","family":"Thill","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, CHU Rouen, Normandie University, UNIROUEN, INSERM 1404, F-76000 Rouen, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0383-2342","authenticated-orcid":false,"given":"Jeremy","family":"Bellien","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, CHU Rouen, Normandie University, UNIROUEN, INSERM U1096, F-76000 Rouen, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0429-8222","authenticated-orcid":false,"given":"Veronique","family":"Le Cam Duchez","sequence":"additional","affiliation":[{"name":"Vascular Hemostasis Unit, CHU Rouen, Normandie University, UNIROUEN, INSERM U1096, F-76000 Rouen, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean","family":"Selim","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care, CHU Rouen, Normandie University, UNIROUEN, INSERM U1096, F-76000 Rouen, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3708-1460","authenticated-orcid":false,"given":"Fabienne","family":"Tamion","sequence":"additional","affiliation":[{"name":"Medical Intensive Care Unit, CHU Rouen, Normandie University, UNIROUEN, INSERM U1096, F-76000 Rouen, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Clavier","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care, CHU Rouen, Normandie University, UNIROUEN, INSERM U1096, F-76000 Rouen, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0267-0986","authenticated-orcid":false,"given":"Emmanuel","family":"Besnier","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care, CHU Rouen, Normandie University, UNIROUEN, INSERM U1096, F-76000 Rouen, France"},{"name":"Centre d\u2019Investigation Clinique, CHU Rouen, F-76000 Rouen, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,3]]},"reference":[{"key":"ref_1","unstructured":"(2022, February 28). WHO Coronavirus (COVID-19) Dashboard. Available online: https:\/\/covid19.who.int."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1007\/s10238-020-00648-x","article-title":"Organ-specific manifestations of COVID-19 infection","volume":"20","author":"Gavriatopoulou","year":"2020","journal-title":"Clin. Exp. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1111\/ijlh.13500","article-title":"COVID-19: Thrombosis, Thromboinflammation, and Anticoagulation Considerations","volume":"43","author":"Levy","year":"2021","journal-title":"Int. J. Lab. Hematol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2110","DOI":"10.1111\/jth.14981","article-title":"COVID-19: A Collision of Complement, Coagulation and Inflammatory Pathways","volume":"18","author":"Chauhan","year":"2020","journal-title":"J. Thromb. Haemost."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"268","DOI":"10.7326\/M20-2003","article-title":"Autopsy Findings and Venous Thromboembolism in Patients with COVID-19: A Prospective Cohort Study","volume":"173","author":"Wichmann","year":"2020","journal-title":"Ann. Intern. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1111\/joim.13300","article-title":"Cause of Death Based on Systematic Post-Mortem Studies in Patients with Positive SARS-CoV-2 Tissue PCR during the COVID-19 Pandemic","volume":"290","author":"Romanova","year":"2021","journal-title":"J. Intern. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2066","DOI":"10.1111\/jth.14876","article-title":"Uncertainties on the Prognostic Value of D-Dimers in COVID-19 Patients","volume":"18","author":"Gris","year":"2020","journal-title":"J. Thromb. Haemost."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1055\/a-1346-3178","article-title":"Hemostasis in Coronavirus Disease 2019\u2014Lesson from Viscoelastic Methods: A Systematic Review","volume":"121","author":"Slomka","year":"2021","journal-title":"Thromb. Haemost."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1080\/09537104.2021.1881949","article-title":"Rotational Thromboelastometry (ROTEM) Profiling of COVID-19 Patients","volume":"32","author":"Mitrovic","year":"2021","journal-title":"Platelets"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s12959-021-00263-0","article-title":"Pathological Findings in Rotation Thromboelastometry Associated with Thromboembolic Events in COVID-19 Patients","volume":"19","author":"Boss","year":"2021","journal-title":"Thromb. J."},{"key":"ref_11","first-page":"10760296211027652","article-title":"Rotational Thromboelastometry Reveals Distinct Coagulation Profiles for Patients with COVID-19 Depending on Disease Severity","volume":"27","author":"Komesli","year":"2021","journal-title":"Clin. Appl. Thromb. Hemost."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.1002\/ajh.25962","article-title":"Evaluation of the Prothrombin Fragment 1.2 in Patients with Coronavirus Disease 2019 (COVID-19)","volume":"95","author":"Song","year":"2020","journal-title":"Am. J. Hematol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1111\/ijlh.13177","article-title":"Reticulated Platelets and Immature Platelet Fraction: Clinical Applications and Method Limitations","volume":"42","author":"Buttarello","year":"2020","journal-title":"Int. J. Lab. Hematol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1007\/s00134-012-2725-7","article-title":"Immature Platelet Fraction in Predicting Sepsis in Critically Ill Patients","volume":"39","author":"Cardelli","year":"2013","journal-title":"Intensive Care Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1111\/bjh.17656","article-title":"Immature Platelets as a Biomarker for Disease Severity and Mortality in COVID-19 Patients","volume":"194","author":"Welder","year":"2021","journal-title":"Br. J. Haematol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1111\/tme.12680","article-title":"Thrombin Generation Assay Is a Useful Pre-Operative Tool to Predict Non-Bleeding Risk in a Patient with Mild Factor V Deficiency","volume":"30","author":"Billoir","year":"2020","journal-title":"Transfus. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1007\/s11239-019-01821-0","article-title":"Thrombin Generation Profile in Non-Thrombotic Factor V Leiden Carriers","volume":"47","author":"Billoir","year":"2019","journal-title":"J. Thromb. Thrombolysis"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"670694","DOI":"10.3389\/fmed.2021.670694","article-title":"Investigation of Coagulation Biomarkers to Assess Clinical Deterioration in SARS-CoV-2 Infection","volume":"8","author":"Billoir","year":"2021","journal-title":"Front. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1016\/j.accpm.2020.10.012","article-title":"French Legal Approach to Patient Consent in Clinical Research","volume":"39","author":"Toulouse","year":"2020","journal-title":"Anaesth. Crit. Care Pain Med."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Gu\u00e9rin, P.J., McLean, A.R.D., Rashan, S., Lawal, A., Watson, J.A., Strub-Wourgaft, N., and White, N.J. (2021). Definitions Matter: Heterogeneity of COVID-19 Disease Severity Criteria and Incomplete Reporting Compromise Meta-Analysis. medRxiv.","DOI":"10.1101\/2021.06.04.21257852"},{"key":"ref_21","unstructured":"National Institutes of Health (2022, February 28). Clinical Spectrum of SARS-CoV-2 Infection\u2014COVID-19 Treatment Guidelines, Available online: https:\/\/www.covid19treatmentguidelines.nih.gov\/overview\/clinical-spectrum\/."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3355","DOI":"10.1038\/s41598-017-03668-y","article-title":"Evaluation of the Immature Platelet Fraction Contribute to the Differential Diagnosis of Hereditary, Immune and Other Acquired Thrombocytopenias","volume":"7","author":"Ferreira","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Reeves, H.M., and Maitta, R.W. (2020). Immature Platelet Dynamics in Immune-Mediated Thrombocytopenic States. Front. Med., 975.","DOI":"10.3389\/fmed.2020.597734"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1111\/ijlh.13499","article-title":"Immature Platelet Fraction over Time and Clinical Outcomes in Patients with Acute Myocardial Infarction","volume":"43","author":"Yahud","year":"2021","journal-title":"Int. J. Lab. Hematol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1055\/s-0039-3400256","article-title":"Immature Platelets as a Predictor of Disease Severity and Mortality in Sepsis and Septic Shock: A Systematic Review","volume":"46","author":"Thorup","year":"2020","journal-title":"Semin. Thromb. Hemost."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1097\/MBC.0b013e32832b1866","article-title":"Prognostic Value of Immature Platelet Fraction and Plasma Thrombopoietin in Disseminated Intravascular Coagulation","volume":"20","author":"Hong","year":"2009","journal-title":"Blood Coagul. Fibrinolysis"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Koyama, K., Katayama, S., Muronoi, T., Tonai, K., Goto, Y., Koinuma, T., Shima, J., and Nunomiya, S. (2018). Time Course of Immature Platelet Count and Its Relation to Thrombocytopenia and Mortality in Patients with Sepsis. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0192064"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1007\/s11239-020-02290-6","article-title":"Immature Platelets in Patients Hospitalized with COVID-19","volume":"51","author":"Cohen","year":"2021","journal-title":"J. Thromb. Thrombolysis"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2720","DOI":"10.1182\/blood.V98.9.2720","article-title":"Interleukin-6 Stimulates Thrombopoiesis through Thrombopoietin: Role in Inflammatory Thrombocytosis","volume":"98","author":"Kaser","year":"2001","journal-title":"Blood"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e61","DOI":"10.1111\/bjh.16850","article-title":"COVID-19-Associated Immune Thrombocytopenia","volume":"190","author":"Bomhof","year":"2020","journal-title":"Br. J. Haematol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1080\/09537104.2020.1754383","article-title":"Association between Platelet Parameters and Mortality in Coronavirus Disease 2019: Retrospective Cohort Study","volume":"31","author":"Liu","year":"2020","journal-title":"Platelets"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1007\/s00277-020-04019-0","article-title":"Mechanism of Thrombocytopenia in COVID-19 Patients","volume":"99","author":"Xu","year":"2020","journal-title":"Ann. Hematol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1001\/jama.283.8.1038","article-title":"A 3-Level Prognostic Classification in Septic Shock Based on Cortisol Levels and Cortisol Response to Corticotropin","volume":"283","author":"Annane","year":"2000","journal-title":"JAMA"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1111\/jth.14859","article-title":"D-Dimer Levels on Admission to Predict in-Hospital Mortality in Patients with COVID-19","volume":"18","author":"Zhang","year":"2020","journal-title":"J. Thromb. Haemost."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.thromres.2020.08.032","article-title":"Admission D-Dimer Levels, D-Dimer Trends, and Outcomes in COVID-19","volume":"196","author":"Naymagon","year":"2020","journal-title":"Thromb. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.thromres.2020.08.030","article-title":"Higher Procoagulatory Potential but Lower DIC Score in COVID-19 ARDS Patients Compared to Non-COVID-19 ARDS Patients","volume":"196","author":"Hoechter","year":"2020","journal-title":"Thromb. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1747","DOI":"10.1111\/jth.14854","article-title":"The Procoagulant Pattern of Patients with COVID-19 Acute Respiratory Distress Syndrome","volume":"18","author":"Ranucci","year":"2020","journal-title":"J. Thromb. Haemost."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.jamcollsurg.2020.05.007","article-title":"Fibrinolysis Shutdown Correlation with Thromboembolic Events in Severe COVID-19 Infection","volume":"231","author":"Wright","year":"2020","journal-title":"J. Am. Coll. Surg."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Ranucci, M., Sitzia, C., Baryshnikova, E., Di Dedda, U., Cardani, R., Martelli, F., and Corsi Romanelli, M. (2020). COVID-19-Associated Coagulopathy: Biomarkers of Thrombin Generation and Fibrinolysis Leading the Outcome. J. Clin. Med., 9.","DOI":"10.21203\/rs.3.rs-52214\/v1"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1111\/jth.15191","article-title":"The ADAMTS13-von Willebrand Factor Axis in COVID-19 Patients","volume":"19","author":"Mancini","year":"2021","journal-title":"J. Thromb. Haemost."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1111\/jth.15230","article-title":"Thrombotic Thrombocytopenic Purpura (TTP) Response Following COVID-19 Infection: Implications for the ADAMTS-13-von Willebrand Factor Axis","volume":"19","author":"Maharaj","year":"2021","journal-title":"J. Thromb. Haemost."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2153","DOI":"10.1182\/blood-2013-08-508093","article-title":"Active von Willebrand Factor Predicts 28-Day Mortality in Patients with Systemic Inflammatory Response Syndrome","volume":"123","author":"Hyseni","year":"2014","journal-title":"Blood"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2193","DOI":"10.1111\/jth.15445","article-title":"Imbalanced of von Willebrand Factor and ADAMTS13 Axis Is Rather a Biomarker of Strong Inflammation and Endothelial Damage than a Cause of Thrombotic Process in Critically-Ill COVID-19 Patients","volume":"19","author":"Joly","year":"2021","journal-title":"J. Thromb. Haemost."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/11\/5\/1383\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:31:08Z","timestamp":1760135468000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/11\/5\/1383"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,3]]},"references-count":43,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2022,3]]}},"alternative-id":["jcm11051383"],"URL":"https:\/\/doi.org\/10.3390\/jcm11051383","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,3]]}}}