Venous thromboembolism in childhood: a prospective two-year registry in The Netherlands.

OBJECTIVE: To study the incidence, signs and symptoms, diagnostic tests, risk factors, therapy, and complications of pediatric venous thromboembolism (VTE) in The Netherlands. METHODS: A prospective 2-year registry of VTE in children aged < or = 18 years. RESULTS: Ninety-nine patients were registered. The annual incidence of VTE was 0.14/10,000 children, 35% of whom were symptom free. Almost half of the patients were newborns. Neonatal VTE was almost exclusively catheter related, located in the upper venous system, and asymptomatic. In older children VTE was catheter related in approximately one third and more often was located in the lower venous system. In 85% of all patients, thrombosis developed while the patient was in the hospital. Diagnosis was usually made by ultrasonography. In 98% of all patients, at least 1 risk factor was present. Congenital prothrombotic disorders were more often present in older children (21%) than in neonates (6%). A variety of treatment modalities were used. Morbidity consisted of bleeding (7%) and recurrent thrombosis (7%). Two children died as result of VTE. CONCLUSION: VTE is mostly diagnosed in hospitalized children, especially sick newborns with central venous catheters and older children with a combination of risk factors. Primary prevention, optimal treatment, and long-term outcome of pediatric symptomatic and asymptomatic VTE need to be studied.

Carbohydrate-deficient glycoprotein syndrome type 1a: a variant phenotype with borderline cognitive dysfunction, cerebellar hypoplasia, and coagulation disturbances.

An 8-year-old boy is described with borderline cognitive impairment, cerebellar hypoplasia, a stroke-like episode, and venous thrombosis of the left leg after a period of immobilization. The pattern of multiple abnormalities in blood coagulation suggested carbohydrate-deficient glycoprotein syndrome type 1a. Isoelectric focusing of serum transferrin was abnormal. The activity of phosphomannomutase in leukocytes and fibroblasts was decreased. Mutation analysis of the PMM2 gene revealed the R141H/E151G genotype. These results confirm the presence of carbohydrate-deficient glycoprotein syndrome type 1a without severe psychomotor retardation.

Acquired protein S deficiency caused by estrogen treatment of tall stature.

OBJECTIVE: To evaluate the potential thrombogenic changes in the coagulation and fibrinolytic system related to treatment with ethinyl estradiol (200 and 300 microg). SUBJECTS AND METHODS: Twenty-five healthy girls with expected final height exceeding 185 cm, as calculated by the method of Bayley and Pinneau, were treated with 200 microg or 300 microg of ethinyl estradiol. Coagulation and fibrinolytic parameters were determined before and during estrogen treatment and 2 and 4 weeks after estrogen withdrawal. RESULTS: No difference in the effects on hemostasis was found between the 2 treatment groups. All 25 patients developed protein S deficiency during estrogen treatment, which in most girls lasted for 4 weeks after cessation of estrogen administration. During therapy, protein C activity increased, whereas antithrombin did not change. Plasminogen and plasmin-alpha(2) antiplasmin complexes significantly increased. Protein S deficiency was accompanied by significantly increased prothrombin fragment 1+2 and fibrinopeptide A. In contrast, thrombin-antithrombin complexes did not change. CONCLUSION: High-dose estrogen treatment to reduce the final height in tall girls is associated with a reversible acquired protein S deficiency with indications of a pre-thrombotic state. Risk of venous thrombo-embolism may be enhanced, especially when additional risk factors for thrombosis are present.