Determinants and Time Course of the Postthrombotic Syndrome after Acute Deep Venous Thrombosis

18 November 2008 | Volume 149 Issue 10 | Pages 698-707

Background: The reason some patients with deep venous thrombosis (DVT) develop the postthrombotic syndrome is not well understood.

Objective: To determine the frequency, time course, and predictors of the postthrombotic syndrome after acute DVT.

Design: Prospective, multicenter cohort study.

Setting: 8 Canadian hospital centers.

Patients: 387 outpatients and inpatients who received an objective diagnosis of acute symptomatic DVT were recruited from 2001 to 2004.

Measurements: Standardized assessments for the postthrombotic syndrome using the Villalta scale at 1, 4, 8, 12, and 24 months after enrollment. Mean postthrombotic score and severity category at each interval was calculated. Predictors of postthrombotic score profiles over time since diagnosis of DVT were identified by using linear mixed modeling.

Results: At all study intervals, about 30% of patients had mild (score, 5 to 9), 10% had moderate (score, 10 to 14), and 3% had severe (score >14 or ulcer) postthrombotic syndrome. Greater postthrombotic severity category at the 1-month visit strongly predicted higher mean postthrombotic scores throughout 24 months of follow-up (1.97, 5.03, and 7.00 increase in Villalta score for mild, moderate, and severe 1-month severity categories, respectively, vs. none; P < 0.001). Additional predictors of higher scores over time were venous thrombosis of the common femoral or iliac vein (2.23 increase in score vs. distal [calf] venous thrombosis; P < 0.001), higher body mass index (0.14 increase in score per kg/m²; P < 0.001), previous ipsilateral venous thrombosis (1.78 increase in score; P = 0.001), older age (0.30 increase in score per 10-year age increase; P = 0.011), and female sex (0.79 increase in score; P = 0.020).

Limitations: Decisions to prescribe compression stockings were left to treating physicians rather than by protocol. Because international normalized ratio data were unavailable, the relationship between anticoagulation quality and Villalta scores could not be assessed.

Conclusion: The postthrombotic syndrome occurs frequently after DVT. Patients with extensive DVT and those with more severe postthrombotic manifestations 1 month after DVT have poorer long-term outcomes.

Editors' Notes Context Chronic leg symptoms after deep venous thrombosis (DVT) (the postthrombotic syndrome) are common but difficult to predict during the acute episode. Contribution By using a standardized scale, the authors periodically evaluated leg symptoms in 387 patients for 2 years after DVT. At each study interval, mild, moderate, and severe postthrombotic syndrome occurred in 30%, 10%, and 3%, respectively, but severity fluctuated over time in individual patients. Age, previous DVT, more extensive DVT, and severity at 1 month were the best predictors of long-term severity. Caution Compression stocking use varied, and anticoagulation effectiveness (for example, international normalized ratio) was unavailable. Implication The postthrombotic syndrome is common and has a variable course and several known risk factors. —The Editors

 

Author and Article Information

From the Centre for Clinical Epidemiology and Community Studies and Jewish General Hospital, McGill University Health Centre and McGill University, and Centre Hospitalier de l'Université de Montréal and Université de Montréal, Montreal, Quebec, Canada; Henderson Research Centre and McMaster University Medical Center, McMaster University, Hamilton, Ontario, Canada; Centre Hospitalier Pierre-Boucher, Longueuil, Quebec, Canada; Université Laval, Quebec City, Quebec, Canada; and Health Services Research Unit, London School of Hygiene & Tropical Medicine, London, United Kingdom.

Acknowledgment: The authors thank the VETO (VEnous Thrombosis Outcomes) study personnel at the clinical study sites for their dedication to this project.

Grant Support: By the Fonds de la recherche en santé du Québec and by an unrestricted grant-in-aid from GlaxoSmithKline. Drs. Kahn and Shrier are recipients of Senior Clinical Investigator Awards from the Fonds de la recherche en santé du Québec. Dr. Johri received a New Investigator Award from the Canadian Institutes of Health Research. Dr. Ginsberg received a Career Award from the Heart and Stroke Foundation of Ontario and holds the David Braley and Nancy Gordon Chair in Thromboembolic Disease at McMaster University.

Potential Financial Conflicts of Interest: None disclosed.

Reproducible Research Statement: Study protocol, statistical code, and data set: Available to approved individuals through written agreements with the author by contacting Dr. Kahn (e-mail, susan.kahn{at}mcgill.ca.)

Requests for Single Reprints: Susan R. Kahn, MD, MSc, Centre for Clinical Epidemiology and Community Studies, Sir Mortimer B. Davis Jewish General Hospital, 3755 Cote Sainte Catherine, Room A-127, Montreal, Quebec H3T 1E2, Canada; e-mail, susan.kahn{at}mcgill.ca.

Current Author Addresses: Drs. Kahn and Shrier, Mr. Ducruet, and Ms. Arsenault: Centre for Clinical Epidemiology and Community Studies, Sir Mortimer B. Davis Jewish General Hospital, 3755 Côte Sainte- Catherine, Room A-127, Montreal, Quebec H3T 1E2, Canada.

Mr. Julian: Department of Oncology, Henderson Research Centre,McMaster University, 711 Concession Street, Hamilton, Ontario L8V 1C3, Canada.

Drs. Miron, Roussin, and Joyal: Centre Hospitalier de l'Université de Montreal, Hôpital Notre-Dame, 1560 Rue Sherbrooke East, Montreal, Quebec H2L 4M1, Canada.

Dr. Desmarais: Centre Hospitalier Pierre Boucher, Jacques-Cartier Boulevard East, Longueuil, Quebec J4M 2A5, Canada.

Dr. Kassis: Hôpital Maisonneuve-Rosemont, 5415 De l'Assomption Boulevard, Montreal, Quebec H1T 2M4, Canada.

Dr. Solymoss: Division of Hematology, Montreal General Hospital, 1650 Cedar Avenue, Montreal, Quebec H3G 1A4, Canada.

Dr. Lamping: Health Services Research Unit, London School of Hygiene & Tropical Medicine, Keppel Street, London WC1E 7HT, United Kingdom.

Dr. Johri: University of Montreal, 1420 Mont-Royal Boulevard, Montreal, Quebec H2V 4P3, Canada.

Dr. Ginsberg: McMaster University, 1200 Main Street West, Hamilton, Ontario L8N 3Z5, Canada.

Author Contributions: Conception and design: S.R. Kahn, D.L. Lamping, M. Johri, J.S. Ginsberg.

Analysis and interpretation of the data: S.R. Kahn, I. Shrier, J.A. Julian, T. Ducruet.

Drafting of the article: S.R. Kahn, I. Shrier.

Critical revision of the article for important intellectual content: S.R. Kahn, I. Shrier, J.A. Julian, A. Roussin, F. Joyal, J. Kassis, S. Solymoss, D.L. Lamping, M. Johri, J.S. Ginsberg.

Final approval of the article: S.R. Kahn, I. Shrier, J.A. Julian, M.-J. Miron, A. Roussin, S. Desmarais, F. Joyal, J. Kassis, S. Solymoss, M. Johri, J.S. Ginsberg.

Provision of study materials or patients: S.R. Kahn, M.-J. Miron, A. Roussin, S. Desmarais, F. Joyal, J. Kassis, S. Solymoss, J.S. Ginsberg.

Statistical expertise: J.A. Julian, T. Ducruet.

Obtaining of funding: S.R. Kahn.

Administrative, technical, or logistic support: S.R. Kahn, L. Arsenault, M.-J. Miron, A. Roussin, F. Joyal, J. Kassis, D.L. Lamping.

Collection and assembly of data: S.R. Kahn, T. Ducruet, L. Arsenault, M.-J. Miron, A. Roussin, F. Joyal, S. Solymoss, J.S. Ginsberg.

^* Deceased.