Correspondence

Venous Thrombosis in Children

N Engl J Med 2004; 351:2451-2452December 2, 2004

Article

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.2-4 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.
Hôpital de la Cavale Blanche, F-29609 Brest, France

Henri Bounameaux, M.D.
Geneva University Hospital, 1211 Geneva, Switzerland

5 References

1. 1

   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
   Full Text | Web of Science | Medline

2. 2

   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
   Web of Science | Medline

3. 3

   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
   CrossRef | Web of Science | Medline

4. 4

   Schmidt B, Andrew M. Neonatal thrombosis: report of a prospective Canadian and international registry. Pediatrics 1995;96:939-943
   Web of Science | Medline

5. 5

   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
   CrossRef | Web of Science | Medline

Author/Editor Response

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.1-3 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

4 References

1. 1

   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
   Full Text | Web of Science | Medline

2. 2

   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
   Web of Science | Medline

3. 3

   Eichinger S, Minar E, Bialonczyk C, et al. D-dimer levels and risk of recurrent venous thromboembolism. JAMA 2003;290:1071-1074
   CrossRef | Web of Science | Medline

4. 4

   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.
   

Citing Articles (1)

Citing Articles

1. 1

   N. A. Goldenberg. (2008) Thrombophilia States and Markers of Coagulation Activation in the Prediction of Pediatric Venous Thromboembolic Outcomes: A Comparative Analysis with Respect to Adult Evidence. Hematology 2008:1, 236-244
   CrossRef