Abstract
Objectives
Patients hospitalized because of community-acquired-pneumonia (CAP) are at risk of cardiovascular diseases. Although plasma procoagulant imbalance play a role, mechanisms are not completely understood. We aimed to investigate whether there is a measurable state of procoagulant imbalance following inflammation determined by CAP.
Methods
We analyzed blood from 51 CAP patients at admission and 51 healthy subjects (HS) for (i) pro and anticoagulants, (ii) thrombin generation (TG) with or without thrombomodulin (TM), which is the physiologic activator of the protein C anticoagulant pathway and(iii) by assessing the ratio between von Willebrand-factor (VWF) and its protease ADAMTS13. Thirty patients were re-analyzed one month after discharge when CAP was resolved.
Results
Median levels of TG parameters, including the endogenous thrombin potential (ETP), the ETP-TM-ratio (with/without TM), peak-thrombin and velocity index were higher in patients at baseline than HS. In particular, the median (IQR) ETP-TM-ratio in patients vs. HS was 0.88 (0.83–0.91) vs. 0.63 (0.48–0.71), p<0.001. Factor (F)VIII, a potent procoagulant involved in TG was higher in patients at baseline than HS [195 U/dL (100–388) vs. 127(108–145)], p<0.001]. The ratio of VWF/ADAMTS13 was higher at baseline than HS. Cumulatively, the findings indicate a state of pro-coagulant imbalance, which (although reduced), remained high [i.e., ETP-TM-ratio, 0.80 (0.74–0.84); FVIII, 152 U/dL (122–190)] one month after discharge when the infection was resolved.
Conclusions
Patients with CAP possess a state of pro-coagulant imbalance, which remains substantially high, even when the infection is resolved. The findings suggest CAP patients as candidates for antithrombotic prophylaxis even after the resolution of infection. Clinical trials are warranted to assess the benefit/risk ratio of prophylaxis extension.
Acknowledgments
We wish to thank the following: Drs. G. Cozzi, P. Colpani, M. Biganzoli, who helped with the measurement of von Willebrand factor and ADAMTS13, and G.L. Ghilardini, who helped with figures and graphical abstract.
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Research funding: This work was also partially supported by the Italian Ministry of Health, Bando Ricerca Corrente 2020.
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Author contributions: AT conceived the study, reviewed results, and wrote the manuscript. SCR, managed patients and collected clinical data. MC, GM, ES, IM, LB, made laboratory testing. MB, made statistical analysis. VM, FP supervised the study. All authors reviewed data and accepted the manuscript.
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Competing interests: AT reports speaker’s fees from Werfen, Stago and Sobi outside the submitted work. FP reports personal fees from Bioverativ, Grifols, Roche, Sanofi, Sobi, Spark, and Takeda, outside the submitted work. The other authors (SCR, MC, GM, ES, IM, LB, MB, VM) have nothing to disclose.
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Informed consent: Informed consent was obtained from all individuals included in this study.
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Ethical approval: The study was approved by the local Ethics Committee.
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