Fibrinogen and the Prediction of Residual Obstruction Manifested after Pulmonary Embolism Treatment
- Benjamin Planquette1,2,3,
- Olivier Sanchez1,2,3,
- James J. Marsh4,
- Peter G. Chiles4,
- Joseph Emmerich1,5,
- Grégoire Le Gal6,
- Guy Meyer1,2,7,8,
- Tanya Wolfson9,
- Anthony C. Gamst9,
- Roger E. Moore10,
- Gabriel B. Gugiu10 and
- Timothy A. Morris4
- 1Université Paris Descartes, Sorbonne Paris Cité, France
- 2Service de Pneumologie et Soins Intensifs, Hôpital Européen Georges Pompidou, AP-HP, Paris
- 3INSERM UMR-S 1140, Paris
- 4Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of California, San Diego, CA
- 5Médecine Vasculaire – Cardiologie, Centre de Diagnostic et de Thérapeutique, Hôpital Hôtel Dieu, AP-HP, Paris, France
- 6Department of Medicine, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Canada
- 7INSERM CIC-1418, Paris
- 8INSERM UMR-S 970, Paris
- 9Computational and Applied Statistics Laboratory (CASL), San Diego Supercomputer Center; University of California San Diego, San Diego, California
- 10Beckman Research Institute of the City of Hope
- Timothy A. Morris, MD FCCP, Division of Pulmonary, Critical Care and Sleep Medicine, University of California, San Diego Healthcare, 200 West Arbor Drive, San Diego, California 92103-8378. E-mail: t1morris{at}ucsd.edu
Abstract
Residual pulmonary vascular obstruction (RPVO) and chronic thromboembolic pulmonary hypertension (CTEPH) are both long-term complications of acute pulmonary embolism (PE), but it is unknown whether RPVO can be predicted by variants of fibrinogen associated with CTEPH.
We use Akaike Information Criterion to select the best predictive models for RPVO in two prospectively followed cohorts of acute PE patients, using as candidate variables the extent of the initial obstruction, clinical characteristics and fibrinogen-related data. We measured the selected models’ goodness of fit by analysis of deviance and compared models by χ2 test.
RPVO occurred in 29/102 (28.4%) subjects in the first cohort and 46/182 (25.3%) subjects in the second. The best-fit predictive model derived in the first cohort (p=0.0002) and validated in the second cohort (p=0.0005) implicated fibrinogen Bβ-chain monosialylation in the development of RPVO. When the derivation procedure excluded clinical characteristics, fibrinogen Bβ-chain monosialylation remained a predictor of RPVO in the best-fit predictive model (p=0.00003). Excluding fibrinogen characteristics worsened the predictive model (p=0.03).
Fibrinogen Bβ-chain monosialylation, a common structural attribute of fibrin, helped predict RPVO after acute PE. Fibrin structure may contribute to the risk of developing RPVO.
Footnotes
This manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.
Conflict of interest: Dr. SANCHEZ reports grants, personal fees and non-financial support from BAYER, grants and non-financial support from ACTELION, personal fees and non-financial support from BMS-PFIZER, grants, personal fees and non-financial support from MSD, grants from DAIICHI SANKYO, personal fees from CHIESI, non-financial support from BOEHRINGER INGELHEIM, outside the submitted work.
Conflict of interest: Dr. Marsh has nothing to disclose.
Conflict of interest: Dr. Chiles has nothing to disclose.
Conflict of interest: Dr. Emmerich has nothing to disclose.
Conflict of interest: Dr. Le Gal reports other from Portola Pharmaceuticals, other from Boehringer-Ingelheim, other from Pfizer, other from Bristol-Myers Squibb, other from LEO Pharma, other from Daiichi Sankyo, other from Bayer, other from Bayer, other from Pfizer, other from LEO Pharma, other from Sanofi, other from bioMérieux, outside the submitted work.
Conflict of interest: Dr. Meyer reports grants from Bayer, non-financial support from Leo Pharma, non-financial support from BMS-Pfizer, non-financial support from Daiichi Sankyo, outside the submitted work.
Conflict of interest: Ms. Wolfson has nothing to disclose.
Conflict of interest: Dr. Gamst has nothing to disclose.
Conflict of interest: Dr. Moore has nothing to disclose.
Conflict of interest: Dr. Gugiu has nothing to disclose.
Conflict of interest: Dr. Morris reports grants from Bayer Pharmaceuticals, during the conduct of the study; personal fees from Bayer Pharmaceuticals, personal fees from Faegre Baker Daniels, outside the submitted work.
Conflict of interest: Dr. Planquette has nothing to disclose.
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