Venous Thrombosis in Children
http://www.100md.com
《新英格兰医药杂志》
To the Editor: Goldenberg et al. (Sept. 9 issue)1 report interesting data about the usefulness of the D-dimer test to predict outcomes in children after a first thromboembolic event. In children, 95 percent of venous thromboembolic events are secondary to underlying disorders associated with hypercoagulable states: cancer, trauma or surgery, congenital heart disease, and systemic lupus erythematosus.2,3,4 One may expect that the great majority of these children will have persistently abnormal D-dimer levels. Therefore, the clinical usefulness of D-dimer testing in everyday practice to predict the risk of an adverse outcome or a recurrence might be limited to the minority of children who have a venous thromboembolic event without a severe underlying disease.
We believe that the predictive value of D-dimer in this new clinical application is not strong enough to permit management guidelines to be formulated, especially since the children in the study by Goldenberg et al. had a variety of thromboembolic conditions. A useful threshold value for D-dimer in this new clinical application also remains to be determined.5
Marc Righini, M.D.
Geneva University Hospital
1211 Geneva, Switzerland
marc.righini@hcuge.ch
Grégoire Le Gal, M.D.
H?pital de la Cavale Blanche
F-29609 Brest, France
Henri Bounameaux, M.D.
Geneva University Hospital
1211 Geneva, Switzerland
References
Goldenberg NA, Knapp-Clevenger R, Manco-Johnson MJ. Elevated plasma factor VIII and D-dimer levels as predictors of poor outcomes of thrombosis in children. N Engl J Med 2004;351:1081-1088.
Andrew M, David M, Adams M, et al. Venous thromboembolic complications (VTE) in children: first analyses of the Canadian Registry of VTE. Blood 1994;83:1251-1257.
Berube C, Mitchell L, Silverman E, et al. The relationship of antiphospholipid antibodies to thromboembolic events in pediatric patients with systemic lupus erythematosus: a cross-sectional study. Pediatr Res 1998;44:351-356.
Schmidt B, Andrew M. Neonatal thrombosis: report of a prospective Canadian and international registry. Pediatrics 1995;96:939-943.
Le Gal G, Bounameaux H. D-Dimer testing to predict recurrence risk in venous thromboembolism: looking for a useful threshold: a rebuttal. J Thromb Haemost 2004;2:1670-1672.
The authors reply: We agree that most cases of pediatric venous thromboembolism are associated with a prothrombotic risk factor, but most of these risk factors are transient. Neither factor VIII activity nor the D-dimer level was elevated in approximately half of our cohort at the initial follow-up (at three to six months). Furthermore, after adjustment for the presence or absence of a chronic inflammatory condition (present in only 10 percent of children in our cohort), elevated levels of factor VIII, D-dimer, or both remained independently predictive of poor outcomes of thrombosis.
Our findings in children are consistent with the results of other studies in adults.1,2,3 Applying the positive likelihood ratio of 6.1 from our study, and using the cumulative incidence of a poor outcome of 51 percent as an estimate of pretest probability, a child in whom thrombosis has been newly diagnosed who has a factor VIII level above 150 IU per deciliter and a D-dimer level above 500 ng per milliliter would have a post-test probability of a poor outcome of 86 percent.4
Neil A. Goldenberg, M.D.
Marilyn J. Manco-Johnson, M.D.
Mountain States Regional Hemophilia and Thrombosis Center
Aurora, CO 80045-0507
neil.goldenberg@uchsc.edu
References
Kyrle PA, Minar E, Hirschl M, et al. High plasma levels of factor VIII and the risk of recurrent venous thromboembolism. N Engl J Med 2000;343:457-462.
Palareti G, Legnani C, Cosmi B, Guazzaloca G, Pancani C, Coccheri S. Risk of venous thromboembolism recurrence: high negative predictive value of D-dimer performed after oral anticoagulation is stopped. Thromb Haemost 2002;87:7-12.
Eichinger S, Minar E, Bialonczyk C, et al. D-dimer levels and risk of recurrent venous thromboembolism. JAMA 2003;290:1071-1074.
Diagnosis and screening. In: Sackett DL, Straus SE, Richardson WS, Rosenberg W, Haynes RB. Evidence-based medicine: how to practice and teach EBM. 2nd ed. Edinburgh: Churchill Livingstone, 2000:67-93.
We believe that the predictive value of D-dimer in this new clinical application is not strong enough to permit management guidelines to be formulated, especially since the children in the study by Goldenberg et al. had a variety of thromboembolic conditions. A useful threshold value for D-dimer in this new clinical application also remains to be determined.5
Marc Righini, M.D.
Geneva University Hospital
1211 Geneva, Switzerland
marc.righini@hcuge.ch
Grégoire Le Gal, M.D.
H?pital de la Cavale Blanche
F-29609 Brest, France
Henri Bounameaux, M.D.
Geneva University Hospital
1211 Geneva, Switzerland
References
Goldenberg NA, Knapp-Clevenger R, Manco-Johnson MJ. Elevated plasma factor VIII and D-dimer levels as predictors of poor outcomes of thrombosis in children. N Engl J Med 2004;351:1081-1088.
Andrew M, David M, Adams M, et al. Venous thromboembolic complications (VTE) in children: first analyses of the Canadian Registry of VTE. Blood 1994;83:1251-1257.
Berube C, Mitchell L, Silverman E, et al. The relationship of antiphospholipid antibodies to thromboembolic events in pediatric patients with systemic lupus erythematosus: a cross-sectional study. Pediatr Res 1998;44:351-356.
Schmidt B, Andrew M. Neonatal thrombosis: report of a prospective Canadian and international registry. Pediatrics 1995;96:939-943.
Le Gal G, Bounameaux H. D-Dimer testing to predict recurrence risk in venous thromboembolism: looking for a useful threshold: a rebuttal. J Thromb Haemost 2004;2:1670-1672.
The authors reply: We agree that most cases of pediatric venous thromboembolism are associated with a prothrombotic risk factor, but most of these risk factors are transient. Neither factor VIII activity nor the D-dimer level was elevated in approximately half of our cohort at the initial follow-up (at three to six months). Furthermore, after adjustment for the presence or absence of a chronic inflammatory condition (present in only 10 percent of children in our cohort), elevated levels of factor VIII, D-dimer, or both remained independently predictive of poor outcomes of thrombosis.
Our findings in children are consistent with the results of other studies in adults.1,2,3 Applying the positive likelihood ratio of 6.1 from our study, and using the cumulative incidence of a poor outcome of 51 percent as an estimate of pretest probability, a child in whom thrombosis has been newly diagnosed who has a factor VIII level above 150 IU per deciliter and a D-dimer level above 500 ng per milliliter would have a post-test probability of a poor outcome of 86 percent.4
Neil A. Goldenberg, M.D.
Marilyn J. Manco-Johnson, M.D.
Mountain States Regional Hemophilia and Thrombosis Center
Aurora, CO 80045-0507
neil.goldenberg@uchsc.edu
References
Kyrle PA, Minar E, Hirschl M, et al. High plasma levels of factor VIII and the risk of recurrent venous thromboembolism. N Engl J Med 2000;343:457-462.
Palareti G, Legnani C, Cosmi B, Guazzaloca G, Pancani C, Coccheri S. Risk of venous thromboembolism recurrence: high negative predictive value of D-dimer performed after oral anticoagulation is stopped. Thromb Haemost 2002;87:7-12.
Eichinger S, Minar E, Bialonczyk C, et al. D-dimer levels and risk of recurrent venous thromboembolism. JAMA 2003;290:1071-1074.
Diagnosis and screening. In: Sackett DL, Straus SE, Richardson WS, Rosenberg W, Haynes RB. Evidence-based medicine: how to practice and teach EBM. 2nd ed. Edinburgh: Churchill Livingstone, 2000:67-93.