Associations between hemostatic markers and mortality in COVID-19 - Compounding effects of D-dimer, antithrombin and PAP complex
(2022) In Thrombosis Research 213. p.97-104- Abstract
In this single-center cohort study, we applied a panel of laboratory markers to characterize hemostatic function in 217 consecutive patients that underwent testing for COVID-19 as they were admitted to Linköping University Hospital between April and June 2020. In the 96 patients that tested positive for SARS-CoV-2 (COVID-19+), the cumulative incidences of death and venous thromboembolism were 24.0% and 19.8% as compared to 12.4% (p = 0.031) and 11.6% (p = 0.13) in the 121 patients that tested negative (COVID-19-). In COVID-19+ patients, we found pronounced increases in plasma levels of von Willebrand factor (vWF) and fibrinogen. Excess mortality was observed in COVID-19+ patients with the following aberrations in hemostatic markers:... (More)
In this single-center cohort study, we applied a panel of laboratory markers to characterize hemostatic function in 217 consecutive patients that underwent testing for COVID-19 as they were admitted to Linköping University Hospital between April and June 2020. In the 96 patients that tested positive for SARS-CoV-2 (COVID-19+), the cumulative incidences of death and venous thromboembolism were 24.0% and 19.8% as compared to 12.4% (p = 0.031) and 11.6% (p = 0.13) in the 121 patients that tested negative (COVID-19-). In COVID-19+ patients, we found pronounced increases in plasma levels of von Willebrand factor (vWF) and fibrinogen. Excess mortality was observed in COVID-19+ patients with the following aberrations in hemostatic markers: high D-dimer, low antithrombin or low plasmin-antiplasmin complex (PAP) formation, with Odds Ratios (OR) for death of 4.7 (95% confidence interval (CI95) 1.7-12.9; p = 0.003) for D-dimer >0.5 mg/L, 5.9 (CI95 1.8-19.7; p = 0.004) for antithrombin (AT) ˂0.85 kIU/l and 4.9 (CI95 1.3-18.3; p = 0.019) for PAP < 1000 μg/L. Compounding increases in mortality was observed in COVID-19+ patients with combined defects in markers of fibrinolysis and coagulation, with ORs for death of 15.7 (CI95 4.3-57; p < 0.001) for patients with PAP <1000 μg/L and D-dimer >0.5 mg/L and 15.5 (CI95 2.8-87, p = 0.002) for patients with PAP <1000 μg/L and AT ˂0.85 kIU/L. We observed an elevated fraction of incompletely degraded D-dimer fragments in COVID-19+ patients with low PAP, indicating impaired fibrinolytic breakdown of cross-linked fibrin.
(Less)
- author
- Boknäs, Niklas ; Laine, Cia ; Hillarp, Andreas LU ; Macwan, Ankit S ; Gustafsson, Kerstin M LU ; Lindahl, Tomas L and Holmström, Margareta
- publishing date
- 2022-05
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Anticoagulants, Antithrombin III, Antithrombins, Biomarkers, COVID-19, COVID-19 Testing, Cohort Studies, Fibrin Fibrinogen Degradation Products/metabolism, Fibrinolysin/metabolism, Fibrinolysis, Hemostatics, Humans, SARS-CoV-2, alpha-2-Antiplasmin
- in
- Thrombosis Research
- volume
- 213
- pages
- 97 - 104
- publisher
- Elsevier
- external identifiers
-
- scopus:85126517247
- pmid:35316719
- ISSN
- 1879-2472
- DOI
- 10.1016/j.thromres.2022.03.013
- language
- English
- LU publication?
- no
- additional info
- Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.
- id
- 61c785ce-ca17-482e-b67c-cba0ef12c5f1
- date added to LUP
- 2022-08-29 09:59:25
- date last changed
- 2024-04-19 19:46:47
@article{61c785ce-ca17-482e-b67c-cba0ef12c5f1,
abstract = {{<p>In this single-center cohort study, we applied a panel of laboratory markers to characterize hemostatic function in 217 consecutive patients that underwent testing for COVID-19 as they were admitted to Linköping University Hospital between April and June 2020. In the 96 patients that tested positive for SARS-CoV-2 (COVID-19+), the cumulative incidences of death and venous thromboembolism were 24.0% and 19.8% as compared to 12.4% (p = 0.031) and 11.6% (p = 0.13) in the 121 patients that tested negative (COVID-19-). In COVID-19+ patients, we found pronounced increases in plasma levels of von Willebrand factor (vWF) and fibrinogen. Excess mortality was observed in COVID-19+ patients with the following aberrations in hemostatic markers: high D-dimer, low antithrombin or low plasmin-antiplasmin complex (PAP) formation, with Odds Ratios (OR) for death of 4.7 (95% confidence interval (CI95) 1.7-12.9; p = 0.003) for D-dimer >0.5 mg/L, 5.9 (CI95 1.8-19.7; p = 0.004) for antithrombin (AT) ˂0.85 kIU/l and 4.9 (CI95 1.3-18.3; p = 0.019) for PAP < 1000 μg/L. Compounding increases in mortality was observed in COVID-19+ patients with combined defects in markers of fibrinolysis and coagulation, with ORs for death of 15.7 (CI95 4.3-57; p < 0.001) for patients with PAP <1000 μg/L and D-dimer >0.5 mg/L and 15.5 (CI95 2.8-87, p = 0.002) for patients with PAP <1000 μg/L and AT ˂0.85 kIU/L. We observed an elevated fraction of incompletely degraded D-dimer fragments in COVID-19+ patients with low PAP, indicating impaired fibrinolytic breakdown of cross-linked fibrin.</p>}},
author = {{Boknäs, Niklas and Laine, Cia and Hillarp, Andreas and Macwan, Ankit S and Gustafsson, Kerstin M and Lindahl, Tomas L and Holmström, Margareta}},
issn = {{1879-2472}},
keywords = {{Anticoagulants; Antithrombin III; Antithrombins; Biomarkers; COVID-19; COVID-19 Testing; Cohort Studies; Fibrin Fibrinogen Degradation Products/metabolism; Fibrinolysin/metabolism; Fibrinolysis; Hemostatics; Humans; SARS-CoV-2; alpha-2-Antiplasmin}},
language = {{eng}},
pages = {{97--104}},
publisher = {{Elsevier}},
series = {{Thrombosis Research}},
title = {{Associations between hemostatic markers and mortality in COVID-19 - Compounding effects of D-dimer, antithrombin and PAP complex}},
url = {{http://dx.doi.org/10.1016/j.thromres.2022.03.013}},
doi = {{10.1016/j.thromres.2022.03.013}},
volume = {{213}},
year = {{2022}},
}