Heparin-resistant Thrombosis Due to Homozygous Antithrombin Deficiency Treated With Rivaroxaban: A Case Report.

BACKGROUND: Heparin fulfills its anticoagulant action through activation of antithrombin (AT), and thus thrombosis secondary to AT deficiency can be associated with heparin resistance. OBSERVATION: A 12-year-old girl with severe venous thrombosis was referred to us because of undetectable anti-Xa levels despite low-molecular-weight heparin therapy. Laboratory investigations revealed a homozygous AT mutation in the heparin binding site (AT Budapest III). She was subsequently treated with rivaroxaban successfully. CONCLUSIONS: Heparin resistance warrants evaluation for AT deficiency. Rivaroxaban may be considered a valid anticoagulant alternative to low-molecular-weight heparin in these patients.

Growth in HIV-infected children on long-term antiretroviral therapy.

OBJECTIVES: To describe growth in HIV-infected children on long-term antiretroviral therapy (ART) and to assess social, clinical, immunological and virological factors associated with suboptimal growth. METHODS: This observational cohort study included all HIV-infected children at an urban ART site in South Africa who were younger than 5 years at ART initiation and with more than 5 years of follow-up. Growth was assessed using weight-for-age Z-scores (WAZ), height-for-age Z-scores (HAZ) and body mass index (BMI)-for-age Z-scores (BAZ). Children were stratified according to pre-treatment anthropometry and age. Univariate and mixed linear analysis were used to determine associations between independent variables and weight and height outcomes. RESULTS: The majority of the 159 children presented with advanced clinical disease (90%) and immunosuppression (89%). Before treatment underweight, stunting and wasting were common (WAZ<-2 = 50%, HAZ<-2 = 73%, BAZ<-2 = 19%). Weight and BMI improved during the initial 12 months, while height improved over the entire 5-year period. Height at study exit was significantly worse for children with growth impairment at ART initiation (P < 0.001), and infants (<1 year) demonstrated superior improvement in terms of BMI (P = 0.04). Tuberculosis was an independent risk factor for suboptimal weight (P = 0.01) and height (P = 0.02) improvement. Weight gain was also hindered by lack of electricity (P = 0.04). Immune reconstitution and virological suppression were not associated with being underweight or stunted at study endpoint. CONCLUSIONS: Malnutrition was a major clinical concern for this cohort of HIV-infected children. Early ART initiation, tuberculosis co-infection management and nutritional interventions are crucial to ensure optimal growth in HIV-infected children.

Two novel deletions in hypotonia-cystinuria syndrome.

Hypotonia-cystinuria syndrome (HCS) is an autosomal recessive disorder caused by combined deletions of SLC3A1 and PREPL. Clinical features include cystinuria, neonatal hypotonia with spontaneous improvement, poor feeding in neonates, hyperphagia in childhood, growth hormone deficiency, and variable cognitive problems. Only 14 families with 6 different deletions have been reported. Patients are often initially misdiagnosed, while correct diagnosis enables therapeutic interventions. We report two novel deletions, further characterizing the clinical and molecular genetics spectrum of HCS.