Evaluation of the Duration of Therapy for Thrombosis in Children (Kids-DOTT)

Inclusion Criteria:

• Children, aged 0- <21 years at time of enrollment
• Recently-diagnosed (i.e., within 30 days of radiologic diagnosis) of first- episode acute venous thrombosis

Exclusion Criteria:

• 1) Any one of the following:

  1. history of premature birth, if corrected (i.e., post-conceptional) age < 36 weeks (including gestation) at time of enrollment;
  2. pregnancy at time of enrollment (N.B.: development of pregnancy while on study will constitute post-enrollment exclusion from the study, although any data collected to that time will be retained given the intent-to-treat analytic approach);
  3. known pulmonary embolism complicating this first-episode venous thrombosis;
  4. uncorrected anatomic vascular defect, including May-Thurner anomaly, cervical rib, and atretic IVC;
  5. use of thrombolytic therapy (i.e. tPA) in the treatment of this first-episode venous thrombosis;
  6. chronic inflammatory condition/disease, other than diabetes mellitus;
  7. prior episode of treated VTE;
  8. antiphospholipid antibody persistent at 6 weeks (anticardiolipin IgM ≥ 20, anti-beta-2-glycoprotein-1 IgG or IgM ≥ 10, or lupus anticoagulant positive by local laboratory parameters, e.g. LA1/LA2 ratio ≥ 1.2 by dRVVT);
  9. combined elevation of factor VIII > 150 IU/dL and D-dimer > 500 ng/mL at diagnosis in patients with veno-occlusive DVT involving the extremities, iliac veins, IVC, subclavian vein, brachiocephalic vein, innominate vein, or SVC;
  10. history of malignancy;
  11. no identifiable clinical risk factor for thrombosis (i.e., episode is spontaneous);
  12. homozygous factor V Leiden mutation;
  13. homozygous prothrombin 20210 mutation;
  14. protein C below lower limit of normal values for age (local laboratory, if patient is < 3 months of age) or protein C less than 40% (IU/dL)if the patient is ≥ 3 months of age;
  15. protein S below 40% (IU/dL);
  16. antithrombin below lower limit of normal values for age (local laboratory, if patient is < 3 months of age) or antithrombin less than 60 % (IU/dL) if the patient is 3 months of age or older at time of enrollment for patients who will be treated with dalteparin (FRAGMIN®);
  17. Two or more separate, non-contiguous thrombi simultaneously;
  18. Systemic lupus erythematosus (SLE);

  19. DALTEPARIN SUBSTUDY ONLY: estimated creatinine clearance <60ml/min. or the patient weighs 8 kg at the time of enrollment.

      • OR

• 2) At least three of the following:

  1. first-degree family history of VTE (full sibling or biological parent treated for VTE before 50 years of age);

  2. thrombophilia traits at most recent assessment prior to enrollment as follows (each counted individually as one risk factor):

     1. factor V Leiden mutation;
     2. prothrombin 20210 mutation;
     3. protein C below lower limit of normal values for age (local laboratory, if patient is < 3 months of age), or protein C less than 40% (IU/dL) if patient is ≥ 3 months);
     4. protein S below 40%;
     5. antithrombin below lower limit of normal values for age (local laboratory, if patient is < 3 months of age) or antithrombin less than 60% (IU/dL) if patient is ≥ 3 months);
     6. homocysteine ≥ 14 microM;
     7. antiphospholipid antibody positive at enrollment; (anticardiolipin IgM ≥ 20); GPL/MPL, anti-beta-2- glycoprotein-1 IgG or IgM ≥ 10 GPL/MPL, or lupus anticoagulant positive by local laboratory parameters,e.g.LA1/LA2 ration ≥ 1.2 by dRVVT).