Abstract
Background: Thrombosis is a frequent and severe complication in patients with coronavirus disease 2019 (COVID-19) admitted to the intensive care unit (ICU). Lupus anticoagulant (LA) is a strong acquired risk factor for thrombosis in various diseases and is frequently observed in patients with COVID-19. Whether LA is associated with thrombosis in patients with severe COVID-19 is currently unclear.
Objective: To investigate if LA is associated with thrombosis in critically ill patients with COVID-19.
Patients/Methods: The presence of LA and other antiphospholipid antibodies was assessed in patients with COVID-19 admitted to the ICU. LA was determined with dilute Russell's viper venom time (dRVVT) and LA-sensitive activated partial thromboplastin time (aPTT) reagents.
Results: Of 169 patients with COVID-19, 116 (69%) tested positive for at least one antiphospholipid antibody upon admission to the ICU. Forty (24%) patients tested positive for LA; of whom 29 (17%) tested positive with a dRVVT, 19 (11%) tested positive with an LA-sensitive aPTT, and 8 (5%) tested positive on both tests. Fifty-eight (34%) patients developed thrombosis after ICU admission. The odds ratio (OR) for thrombosis in patients with LA based on a dRVVT was 2.5 (95% confidence interval [CI], 1.1-5.7), which increased to 4.5 (95% CI, 1.4-14.3) in patients at or below the median age in this study (64 years). LA positivity based on a dRVVT or LA-sensitive aPTT was only associated with thrombosis in patients aged less than 65 years (OR, 3.8; 95% CI, 1.3-11.4) and disappeared after adjustment for C-reactive protein.
Conclusion: Lupus anticoagulant on admission is strongly associated with thrombosis in critically ill patients with COVID-19, especially in patients aged less than 65 years.
| Original language | English |
|---|---|
| Article number | e12809 |
| Journal | Research and practice in thrombosis and haemostasis |
| Volume | 6 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Aug 2022 |
Keywords
- COVID-19
- critically ill
- lupus anticoagulant
- risk factor
- thrombosis
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In: Research and practice in thrombosis and haemostasis, Vol. 6, No. 6, e12809, 08.2022.
Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - Lupus anticoagulant associates with thrombosis in patients with COVID-19 admitted to intensive care units
T2 - A retrospective cohort study
AU - Noordermeer, Tessa
AU - Schutgens, Roger E G
AU - Visser, Chantal
AU - Rademaker, Emma
AU - de Maat, Moniek P M
AU - Jansen, A J Gerard
AU - Limper, Maarten
AU - Cremer, Olaf L
AU - Kruip, Marieke J H A
AU - Endeman, Henrik
AU - Maas, Coen
AU - de Laat, Bas
AU - Urbanus, Rolf T
N1 - Funding Information: This study was funded by grants of the Netherlands Thrombosis Foundation (2020_A & 2018-03) and the Netherlands Organization for Health Research and Development (project number 10430012010004). Consortium Members Dutch COVID & Thrombosis Coalition: Amsterdam University Medical Center: Location AMC; Prof. Dr. D. van de Beek, neurologist; Dr. M. C. Brouwer, neurologist; Dr. S. de Bruin, PhD candidate; Dr. M. Coppens, internist vascular medicine; Dr. N. van Es, PhD candidate; Dr. T. F. van Haaps, PhD candidate, Department of Vascular Medicine; Prof. Dr. N. P. Juffermans, intensivist; Dr. M. C. A. Muller, intensivist; Prof. Dr. A. P. J. Vlaar, intensivist. Location VUMC: Prof. Dr. C. M. P. M. Hertogh, nursing home specialist; Prof. Dr. L. M. A. Heunks, professor intensive care; Dr. J. G. Hugtenburg, pharmacologist; Dr. J. van Kooten, nursing home specialist; Dr. E. J. Nossent, pulmonologist; Prof. Dr. Y. Smulders, internist; Dr. P. R. Tuinman, intensivist; Dr. A. Vonk Noordegraaf, pulmonologist. Amphia Hospital: Dr. M. J. J. H. Grootenboers, pulmonologist; Dr. C van Guldener, internist; Dr. M. Kant, pulmonologist. Argos Zorggroep: Dr. A. Lansbergen, physiotherapist. Deventer Hospital: Dr. J. Faber, coordinator of the Research Department; Dr. G. Hajer, internist vascular medicine. Dr. A. Stemerdink, intensivist. Erasmus University Medical Center: Dr. J. van den Akker, intensivist: Dr. R. Bierings, cellular biologist, Department of Hematology; Dr. H. Endeman, intensivist; Dr. M. Goeijenbier, internal medicine, Department of Viroscience; Dr. N. G. M. Hunfeld, hospital Pharmacist; Prof. Dr. E. C. M. van Gorp, infectious diseases specialist, Department of Viroscience; Prof. Dr. D. A. M. P. J. Gommers, intensivist; Prof. Dr. M.P.G. Koopmans, veterinarian-virologist, Department of Viroscience; Dr. M. J. H. A. Kruip, hematologist; Prof. Dr. T. Kuiken, professor of comparative pathology, Department of Viroscience; Dr. T. Langerak, PhD candidate, Department of Viroscience; Prof. Dr. Leebeek, professor of hemostasis and thrombosis; Dr. M. N. Lauw, hematologist, Department of Hematology; Prof. Dr. M. P. M. de Maat, biochemist, Department of Hematology; Dr. D. Noack, PhD candidate i.o. Department of Viroscience; Dr. M.S. Paats, pulmonologist; Dr. M. P. Raadsen, PhD candidate, Department of Viroscience; Dr. B. Rockx, assistant professor, Department of Viroscience; Dr. C. Rokx, infectious diseases specialist; Dr. C. A. M. Schurink, infectious diseases specialist; Dr. K. Tong-Minh, PhD candidate, Department of Viroscience; Dr. L. van den Toorn, pulmonologist; Dr. C. A. den Uil, cardiologist-intensivist; Dr. C. Visser, PhD candidate, Department of Hematology; Farmadam: Dr. F. Boutkourt, PhD candidate; Dr. T. Roest, pharmacist; Flevoziekenhuis: Dr. R. A. Douma, infectious diseases specialist; Dr. L. R. de Haan, PhD candidate; Dr. M. ten Wolde, internist vascular medicine; Hospital de Gelderse Vallei: Dr. R. H. H. Bemelmans, internist; Dr. B. Festen, intensivist; Ikazia Hospital: Dr. S. Stads, intensivist; Jeroen Bosch Hospital: Dr. C. P. C. de Jager, intensivist; Dr. K.S. Simons, intensivist; Leids University Medical Center: Drs. M. L. Antoni, cardiologist, Department of Cardiology; Dr. M. H. Bos, biochemicus, associate professor, Department of Medicine–Thrombosis and Hemostasis; Drs. J. L. I. Burggraaf, PhD candidate, Department of Clinical Epidemiology; Prof. S. C. Cannegieter, clinical epidemiologist, Department of Medicine–Thrombosis and Hemostasis and Department of Clinical Epidemiology; Prof. Dr. H. C. J. Eikenboom, hematologist/internist vascular medicine, Department of Medicine–Thrombosis and Hemostasis; Dr. P. L. den Exter, vascular medicine specialist, Department of Medicine–Thrombosis and Hemostasis; Dr. J. J. M. Geelhoed, pulmonologist, Department of Pulmonology; Prof. Dr. M. V. Huisman, internist vascular medicine, Department of Medicine–Thrombosis and Hemostasis; Prof. E. de Jonge, internist-intensivist, Department of Intensive Care Medicine; Dr. F. H. J. Kaptein, PhD candidate, Department of Medicine–Thrombosis and Hemostasis; Dr. F. A. Klok, internist vascular medicine, Department of Medicine–Thrombosis and Hemostasis; Dr. L. J. M. Kroft, radiologist, Department of Radiology; Dr. W. M. Lijfering, clinical epidemiologist, Department of Medicine–Thrombosis and Hemostasis; Dr. L. Nab, PhD candidate, Department of Clinical Epidemiology; Dr. M. K. Ninaber, pulmonologist, Department of Pulmonology; Prof. Dr. H. Putter, statistician, Department of Biomedical Data Sciences; Dr. S. R. S. Ramai, pulmonologist, Department of Pulmonology; Dr. A. M. da Rocha Rondon, postdoctoral researcher, Department of Medicine–Thrombosis and Hemostasis; Dr. A. H. E. Roukens, infectious diseases specialist, Department of Infectious Diseases; Dr. M. A. M. Stals, PhD candidate, Department of Medicine–Thrombosis and Hemostasis; Prof. Dr. H. H. Versteeg, cellular biologist, Department of Medicine–Thrombosis and Hemostasis; Dr. H. W. Vliegen, cardiologist, Department of Cardiology; Dr. B. J. M. van Vlijmen, cellular biologist, Department of Medicine–Thrombosis and Hemostasis. Maastricht University Medical Center: Dr. T. van de Berg, PhD candidate; Dr. R. Bruggemann, PhD candidate; Dr. B. C. T. van Bussel, internist-intensivist; Prof. Dr. H. ten Cate, internist; Dr. A. ten Cate-Hoek, clincial epidemiologist and medical director of Thrombosis Service Maastricht; Prof. Dr. T. M. Hackeng, biochemist; Dr. ir. Y. Henskens, clinical chemist; Dr. A. Hulshof, PhD candidate; Dr. M. Mulder, PhD candidate; Dr. R. H. Olie, internist vascular medicine; Prof. Dr. L. Schurgers, biochemist; Dr. B. Spaetgens, internist subspecialised in geriatrics; Dr. H. Spronk, biochemist; Prof. Dr. M. A. Spruit, executive board member Ciro and professor in rehabilitation; Dr. K. Winckers, internist vascular medicine. Maxima Medical Center: Dr. L. Nieuwenhuizen, hematologist. Medical Center Leeuwaarden; Dr. B. Franken, hematologist; Dr. I. M. Schrover, internist vascular medicine; Dr. E. G. M. de Waal, hematologist. Medical Center Twente; Dr. A. Beishuizen, intensivist; Dr. A. Cornet, intensivist; Dr. J. Krabbe, clinical biochemist. Radboud University Medical Center: Prof. dr. K. Kramers, professor medical safety; Dr. J. Leentjens, internist vascular medicine; Dr. Q. de Mast, infectious diseases specialist; Prof. dr. S. Middeldorp, internist vascular medicine. Reinier de Graaf Gasthuis Hospital: Dr. R. E. Brouwer, hematologist; Dr. J. L. J. Ellerbroek, infectious diseases specialist; Dr. J. Tijmensen, hematologist. Rijnstate Hospital; Dr. M. M. C. Hovens, internist vascular medicine; Dr. E. A. N. Oostdijk, intensivist; Drs. B. D. Westerhof, anesthesiologist-intensivist. Rode Kruis Hospital; Dr. L. M. Faber, hematologist. Sanquin Research, Amsterdam: Dr. M. van den Biggelaar, head of Laboratory of Proteomics, Department of Molecular and Cellular Hemostasis; Prof. Dr. J. C. M. Meijers, biochemist (and Amsterdam University Medical Centers); Prof. Dr. J. Voorberg, molecular and cellular biologist (and Amsterdam University Medical Centers). St Fransiscus Gasthuis & Vlietland Hospital: Dr. M. E. Kevenaar, internist; Dr. Y. L. Soei, internist; Dr. E. J. Wils, intensivist. St. Jansdal Hospital: Dr. F. N. Croles, hematologist. Synapse Research Institute: Dr. B. de Laat, biochemist, director. Tergooi Hospital: Prof. Dr. P. W. Kamphuisen, internist vascular medicine: Dr. R. Vink, intensivist. University Medical Center Groningen: Prof. Dr. T. Lisman, biochemist; Prof. Dr. K. Meijer, hematologist, Department Hematology; Dr. Y. I. G. van Tichelaar, internist. University Medical Center Utrecht: Prof. Dr. O. L. Cremer, anesthesiologist-intensivist; Dr. G. Geersing, general practicioner, Julius Center, Department of Primary Care; Prof Dr. H. A. H. Kaasjager, internist vascular medicine; Dr. N. Kusadasi, hematologist-intensivist; Dr. A. Huisman, clinical biochemist; Dr. C. Maas, principal investigator Coagulation & Fibrinolysis; Dr. M. Nijkeuter, internist vascular medicine; Prof. Dr. R.E.G. Schutgens, hematologist, Van Creveldkliniek; Dr. R. T. Urbanus, biochemist, Van Creveldkliniek; Dr. J. Westerink, internist vascular medicine.Wilhelmina Hospital Assen: Dr. H. J. Faber, internist-intensivist. Zaans Medical Center: Dr. S. C. E. Koster, anesthesiologist-intensivist. Zuyderland Hospital: Dr. P. van Montfort, resident internal medicine; Dr. D. J. L. van Twist, internist vascular medicine. Funding Information: This study was funded by grants of the Netherlands Thrombosis Foundation (2020_A & 2018‐03) and the Netherlands Organization for Health Research and Development (project number 10430012010004). Publisher Copyright: © 2022 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH).
PY - 2022/8
Y1 - 2022/8
N2 - Background: Thrombosis is a frequent and severe complication in patients with coronavirus disease 2019 (COVID-19) admitted to the intensive care unit (ICU). Lupus anticoagulant (LA) is a strong acquired risk factor for thrombosis in various diseases and is frequently observed in patients with COVID-19. Whether LA is associated with thrombosis in patients with severe COVID-19 is currently unclear.Objective: To investigate if LA is associated with thrombosis in critically ill patients with COVID-19.Patients/Methods: The presence of LA and other antiphospholipid antibodies was assessed in patients with COVID-19 admitted to the ICU. LA was determined with dilute Russell's viper venom time (dRVVT) and LA-sensitive activated partial thromboplastin time (aPTT) reagents.Results: Of 169 patients with COVID-19, 116 (69%) tested positive for at least one antiphospholipid antibody upon admission to the ICU. Forty (24%) patients tested positive for LA; of whom 29 (17%) tested positive with a dRVVT, 19 (11%) tested positive with an LA-sensitive aPTT, and 8 (5%) tested positive on both tests. Fifty-eight (34%) patients developed thrombosis after ICU admission. The odds ratio (OR) for thrombosis in patients with LA based on a dRVVT was 2.5 (95% confidence interval [CI], 1.1-5.7), which increased to 4.5 (95% CI, 1.4-14.3) in patients at or below the median age in this study (64 years). LA positivity based on a dRVVT or LA-sensitive aPTT was only associated with thrombosis in patients aged less than 65 years (OR, 3.8; 95% CI, 1.3-11.4) and disappeared after adjustment for C-reactive protein.Conclusion: Lupus anticoagulant on admission is strongly associated with thrombosis in critically ill patients with COVID-19, especially in patients aged less than 65 years.
AB - Background: Thrombosis is a frequent and severe complication in patients with coronavirus disease 2019 (COVID-19) admitted to the intensive care unit (ICU). Lupus anticoagulant (LA) is a strong acquired risk factor for thrombosis in various diseases and is frequently observed in patients with COVID-19. Whether LA is associated with thrombosis in patients with severe COVID-19 is currently unclear.Objective: To investigate if LA is associated with thrombosis in critically ill patients with COVID-19.Patients/Methods: The presence of LA and other antiphospholipid antibodies was assessed in patients with COVID-19 admitted to the ICU. LA was determined with dilute Russell's viper venom time (dRVVT) and LA-sensitive activated partial thromboplastin time (aPTT) reagents.Results: Of 169 patients with COVID-19, 116 (69%) tested positive for at least one antiphospholipid antibody upon admission to the ICU. Forty (24%) patients tested positive for LA; of whom 29 (17%) tested positive with a dRVVT, 19 (11%) tested positive with an LA-sensitive aPTT, and 8 (5%) tested positive on both tests. Fifty-eight (34%) patients developed thrombosis after ICU admission. The odds ratio (OR) for thrombosis in patients with LA based on a dRVVT was 2.5 (95% confidence interval [CI], 1.1-5.7), which increased to 4.5 (95% CI, 1.4-14.3) in patients at or below the median age in this study (64 years). LA positivity based on a dRVVT or LA-sensitive aPTT was only associated with thrombosis in patients aged less than 65 years (OR, 3.8; 95% CI, 1.3-11.4) and disappeared after adjustment for C-reactive protein.Conclusion: Lupus anticoagulant on admission is strongly associated with thrombosis in critically ill patients with COVID-19, especially in patients aged less than 65 years.
KW - COVID-19
KW - critically ill
KW - lupus anticoagulant
KW - risk factor
KW - thrombosis
UR - http://www.scopus.com/inward/record.url?scp=85138881677&partnerID=8YFLogxK
U2 - 10.1002/rth2.12809
DO - 10.1002/rth2.12809
M3 - Article
C2 - 36178455
SN - 2475-0379
VL - 6
JO - Research and practice in thrombosis and haemostasis
JF - Research and practice in thrombosis and haemostasis
IS - 6
M1 - e12809
ER -