Serial markers of coagulation and inflammation and the occurrence of clinical pulmonary thromboembolism in mechanically ventilated patients with SARS-CoV-2 infection; the prospective Maastricht intensive care COVID cohort
Abstract Background The incidence of pulmonary thromboembolism is high in SARS-CoV-2 patients admitted to the Intensive Care. Elevated biomarkers of coagulation (fibrinogen and D-dimer) and inflammation (c-reactive protein (CRP) and ferritin) are associated with poor outcome in SARS-CoV-2. Whether t...
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2021-05-01
|
| Series: | Thrombosis Journal |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12959-021-00286-7 |
| _version_ | 1818448776606515200 |
|---|---|
| author | Mark M. G. Mulder LIoyd Brandts Renée A. G. Brüggemann Marcel Koelmann Alexander S. Streng Renske H. Olie Hester A. Gietema Henri M. H. Spronk Iwan C. C. van der Horst Jan-Willem E. M. Sels Joachim E. Wildberger Sander M. J. van Kuijk Ronny M. Schnabel Hugo ten Cate Yvonne M. C. Henskens Bas C. T. van Bussel |
| author_facet | Mark M. G. Mulder LIoyd Brandts Renée A. G. Brüggemann Marcel Koelmann Alexander S. Streng Renske H. Olie Hester A. Gietema Henri M. H. Spronk Iwan C. C. van der Horst Jan-Willem E. M. Sels Joachim E. Wildberger Sander M. J. van Kuijk Ronny M. Schnabel Hugo ten Cate Yvonne M. C. Henskens Bas C. T. van Bussel |
| author_sort | Mark M. G. Mulder |
| collection | DOAJ |
| description | Abstract Background The incidence of pulmonary thromboembolism is high in SARS-CoV-2 patients admitted to the Intensive Care. Elevated biomarkers of coagulation (fibrinogen and D-dimer) and inflammation (c-reactive protein (CRP) and ferritin) are associated with poor outcome in SARS-CoV-2. Whether the time-course of fibrinogen, D-dimer, CRP and ferritin is associated with the occurrence of pulmonary thromboembolism in SARS-CoV-2 patients is unknown. We hypothesise that patients on mechanical ventilation with SARS-CoV-2 infection and clinical pulmonary thromboembolism have lower concentrations of fibrinogen and higher D-dimer, CRP, and ferritin concentrations over time compared to patients without a clinical pulmonary thromboembolism. Methods In a prospective study, fibrinogen, D-dimer, CRP and ferritin were measured daily. Clinical suspected pulmonary thromboembolism was either confirmed or excluded based on computed tomography pulmonary angiography (CTPA) or by transthoracic ultrasound (TTU) (i.e., right-sided cardiac thrombus). In addition, patients who received therapy with recombinant tissue plasminogen activator were included when clinical instability in suspected pulmonary thromboembolism did not allow CTPA. Serial data were analysed using a mixed-effects linear regression model, and models were adjusted for known risk factors (age, sex, APACHE-II score, body mass index), biomarkers of coagulation and inflammation, and anticoagulants. Results Thirty-one patients were considered to suffer from pulmonary thromboembolism ((positive CTPA (n = 27), TTU positive (n = 1), therapy with recombinant tissue plasminogen activator (n = 3)), and eight patients with negative CTPA were included. After adjustment for known risk factors and anticoagulants, patients with, compared to those without, clinical pulmonary thromboembolism had lower average fibrinogen concentration of − 0.9 g/L (95% CI: − 1.6 – − 0.1) and lower average ferritin concentration of − 1045 μg/L (95% CI: − 1983 – − 106) over time. D-dimer and CRP average concentration did not significantly differ, 561 μg/L (− 6212–7334) and 27 mg/L (− 32–86) respectively. Ferritin lost statistical significance, both in sensitivity analysis and after adjustment for fibrinogen and D-dimer. Conclusion Lower average concentrations of fibrinogen over time were associated with the presence of clinical pulmonary thromboembolism in patients at the Intensive Care, whereas D-dimer, CRP and ferritin were not. Lower concentrations over time may indicate the consumption of fibrinogen related to thrombus formation in the pulmonary vessels. |
| first_indexed | 2024-12-14T20:24:53Z |
| format | Article |
| id | doaj.art-6bf3e0501f96462e9844fddbefde782c |
| institution | Directory Open Access Journal |
| issn | 1477-9560 |
| language | English |
| last_indexed | 2024-12-14T20:24:53Z |
| publishDate | 2021-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Thrombosis Journal |
| spelling | doaj.art-6bf3e0501f96462e9844fddbefde782c2022-12-21T22:48:39ZengBMCThrombosis Journal1477-95602021-05-0119111210.1186/s12959-021-00286-7Serial markers of coagulation and inflammation and the occurrence of clinical pulmonary thromboembolism in mechanically ventilated patients with SARS-CoV-2 infection; the prospective Maastricht intensive care COVID cohortMark M. G. Mulder0LIoyd Brandts1Renée A. G. Brüggemann2Marcel Koelmann3Alexander S. Streng4Renske H. Olie5Hester A. Gietema6Henri M. H. Spronk7Iwan C. C. van der Horst8Jan-Willem E. M. Sels9Joachim E. Wildberger10Sander M. J. van Kuijk11Ronny M. Schnabel12Hugo ten Cate13Yvonne M. C. Henskens14Bas C. T. van Bussel15Department of Intensive Care Medicine, Maastricht University Medical Centre+Department of Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Centre+Department of Internal Medicine, Maastricht University Medical Centre+Department of Intensive Care Medicine, Maastricht University Medical Centre+Department of Clinical Chemistry, Central Diagnostic Laboratory, Maastricht University Medical Centre+Department of Internal Medicine, Maastricht University Medical Centre+Department of Radiology and Nuclear Medicine, Maastricht University Medical Centre+Thrombosis Expert Centre Maastricht and Department of Internal Medicine, Section Vascular Medicine, Maastricht University Medical Centre+Department of Intensive Care Medicine, Maastricht University Medical Centre+Department of Intensive Care Medicine, Maastricht University Medical Centre+Cardiovascular Research Institute Maastricht (CARIM), Maastricht UniversityDepartment of Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Centre+Department of Intensive Care Medicine, Maastricht University Medical Centre+Department of Internal Medicine, Maastricht University Medical Centre+Department of Clinical Chemistry, Central Diagnostic Laboratory, Maastricht University Medical Centre+Department of Intensive Care Medicine, Maastricht University Medical Centre+Abstract Background The incidence of pulmonary thromboembolism is high in SARS-CoV-2 patients admitted to the Intensive Care. Elevated biomarkers of coagulation (fibrinogen and D-dimer) and inflammation (c-reactive protein (CRP) and ferritin) are associated with poor outcome in SARS-CoV-2. Whether the time-course of fibrinogen, D-dimer, CRP and ferritin is associated with the occurrence of pulmonary thromboembolism in SARS-CoV-2 patients is unknown. We hypothesise that patients on mechanical ventilation with SARS-CoV-2 infection and clinical pulmonary thromboembolism have lower concentrations of fibrinogen and higher D-dimer, CRP, and ferritin concentrations over time compared to patients without a clinical pulmonary thromboembolism. Methods In a prospective study, fibrinogen, D-dimer, CRP and ferritin were measured daily. Clinical suspected pulmonary thromboembolism was either confirmed or excluded based on computed tomography pulmonary angiography (CTPA) or by transthoracic ultrasound (TTU) (i.e., right-sided cardiac thrombus). In addition, patients who received therapy with recombinant tissue plasminogen activator were included when clinical instability in suspected pulmonary thromboembolism did not allow CTPA. Serial data were analysed using a mixed-effects linear regression model, and models were adjusted for known risk factors (age, sex, APACHE-II score, body mass index), biomarkers of coagulation and inflammation, and anticoagulants. Results Thirty-one patients were considered to suffer from pulmonary thromboembolism ((positive CTPA (n = 27), TTU positive (n = 1), therapy with recombinant tissue plasminogen activator (n = 3)), and eight patients with negative CTPA were included. After adjustment for known risk factors and anticoagulants, patients with, compared to those without, clinical pulmonary thromboembolism had lower average fibrinogen concentration of − 0.9 g/L (95% CI: − 1.6 – − 0.1) and lower average ferritin concentration of − 1045 μg/L (95% CI: − 1983 – − 106) over time. D-dimer and CRP average concentration did not significantly differ, 561 μg/L (− 6212–7334) and 27 mg/L (− 32–86) respectively. Ferritin lost statistical significance, both in sensitivity analysis and after adjustment for fibrinogen and D-dimer. Conclusion Lower average concentrations of fibrinogen over time were associated with the presence of clinical pulmonary thromboembolism in patients at the Intensive Care, whereas D-dimer, CRP and ferritin were not. Lower concentrations over time may indicate the consumption of fibrinogen related to thrombus formation in the pulmonary vessels.https://doi.org/10.1186/s12959-021-00286-7SARS-CoV-2COVID-19Pulmonary embolismPulmonary thrombosisCoagulationD-dimer |
| spellingShingle | Mark M. G. Mulder LIoyd Brandts Renée A. G. Brüggemann Marcel Koelmann Alexander S. Streng Renske H. Olie Hester A. Gietema Henri M. H. Spronk Iwan C. C. van der Horst Jan-Willem E. M. Sels Joachim E. Wildberger Sander M. J. van Kuijk Ronny M. Schnabel Hugo ten Cate Yvonne M. C. Henskens Bas C. T. van Bussel Serial markers of coagulation and inflammation and the occurrence of clinical pulmonary thromboembolism in mechanically ventilated patients with SARS-CoV-2 infection; the prospective Maastricht intensive care COVID cohort Thrombosis Journal SARS-CoV-2 COVID-19 Pulmonary embolism Pulmonary thrombosis Coagulation D-dimer |
| title | Serial markers of coagulation and inflammation and the occurrence of clinical pulmonary thromboembolism in mechanically ventilated patients with SARS-CoV-2 infection; the prospective Maastricht intensive care COVID cohort |
| title_full | Serial markers of coagulation and inflammation and the occurrence of clinical pulmonary thromboembolism in mechanically ventilated patients with SARS-CoV-2 infection; the prospective Maastricht intensive care COVID cohort |
| title_fullStr | Serial markers of coagulation and inflammation and the occurrence of clinical pulmonary thromboembolism in mechanically ventilated patients with SARS-CoV-2 infection; the prospective Maastricht intensive care COVID cohort |
| title_full_unstemmed | Serial markers of coagulation and inflammation and the occurrence of clinical pulmonary thromboembolism in mechanically ventilated patients with SARS-CoV-2 infection; the prospective Maastricht intensive care COVID cohort |
| title_short | Serial markers of coagulation and inflammation and the occurrence of clinical pulmonary thromboembolism in mechanically ventilated patients with SARS-CoV-2 infection; the prospective Maastricht intensive care COVID cohort |
| title_sort | serial markers of coagulation and inflammation and the occurrence of clinical pulmonary thromboembolism in mechanically ventilated patients with sars cov 2 infection the prospective maastricht intensive care covid cohort |
| topic | SARS-CoV-2 COVID-19 Pulmonary embolism Pulmonary thrombosis Coagulation D-dimer |
| url | https://doi.org/10.1186/s12959-021-00286-7 |
| work_keys_str_mv | AT markmgmulder serialmarkersofcoagulationandinflammationandtheoccurrenceofclinicalpulmonarythromboembolisminmechanicallyventilatedpatientswithsarscov2infectiontheprospectivemaastrichtintensivecarecovidcohort AT lioydbrandts serialmarkersofcoagulationandinflammationandtheoccurrenceofclinicalpulmonarythromboembolisminmechanicallyventilatedpatientswithsarscov2infectiontheprospectivemaastrichtintensivecarecovidcohort AT reneeagbruggemann serialmarkersofcoagulationandinflammationandtheoccurrenceofclinicalpulmonarythromboembolisminmechanicallyventilatedpatientswithsarscov2infectiontheprospectivemaastrichtintensivecarecovidcohort AT marcelkoelmann serialmarkersofcoagulationandinflammationandtheoccurrenceofclinicalpulmonarythromboembolisminmechanicallyventilatedpatientswithsarscov2infectiontheprospectivemaastrichtintensivecarecovidcohort AT alexandersstreng serialmarkersofcoagulationandinflammationandtheoccurrenceofclinicalpulmonarythromboembolisminmechanicallyventilatedpatientswithsarscov2infectiontheprospectivemaastrichtintensivecarecovidcohort AT renskeholie serialmarkersofcoagulationandinflammationandtheoccurrenceofclinicalpulmonarythromboembolisminmechanicallyventilatedpatientswithsarscov2infectiontheprospectivemaastrichtintensivecarecovidcohort AT hesteragietema serialmarkersofcoagulationandinflammationandtheoccurrenceofclinicalpulmonarythromboembolisminmechanicallyventilatedpatientswithsarscov2infectiontheprospectivemaastrichtintensivecarecovidcohort AT henrimhspronk serialmarkersofcoagulationandinflammationandtheoccurrenceofclinicalpulmonarythromboembolisminmechanicallyventilatedpatientswithsarscov2infectiontheprospectivemaastrichtintensivecarecovidcohort AT iwanccvanderhorst serialmarkersofcoagulationandinflammationandtheoccurrenceofclinicalpulmonarythromboembolisminmechanicallyventilatedpatientswithsarscov2infectiontheprospectivemaastrichtintensivecarecovidcohort AT janwillememsels serialmarkersofcoagulationandinflammationandtheoccurrenceofclinicalpulmonarythromboembolisminmechanicallyventilatedpatientswithsarscov2infectiontheprospectivemaastrichtintensivecarecovidcohort AT joachimewildberger serialmarkersofcoagulationandinflammationandtheoccurrenceofclinicalpulmonarythromboembolisminmechanicallyventilatedpatientswithsarscov2infectiontheprospectivemaastrichtintensivecarecovidcohort AT sandermjvankuijk serialmarkersofcoagulationandinflammationandtheoccurrenceofclinicalpulmonarythromboembolisminmechanicallyventilatedpatientswithsarscov2infectiontheprospectivemaastrichtintensivecarecovidcohort AT ronnymschnabel serialmarkersofcoagulationandinflammationandtheoccurrenceofclinicalpulmonarythromboembolisminmechanicallyventilatedpatientswithsarscov2infectiontheprospectivemaastrichtintensivecarecovidcohort AT hugotencate serialmarkersofcoagulationandinflammationandtheoccurrenceofclinicalpulmonarythromboembolisminmechanicallyventilatedpatientswithsarscov2infectiontheprospectivemaastrichtintensivecarecovidcohort AT yvonnemchenskens serialmarkersofcoagulationandinflammationandtheoccurrenceofclinicalpulmonarythromboembolisminmechanicallyventilatedpatientswithsarscov2infectiontheprospectivemaastrichtintensivecarecovidcohort AT basctvanbussel serialmarkersofcoagulationandinflammationandtheoccurrenceofclinicalpulmonarythromboembolisminmechanicallyventilatedpatientswithsarscov2infectiontheprospectivemaastrichtintensivecarecovidcohort |