Patterns of joint damage in severe haemophilia A treated with prophylaxis.

Objective: The primary objective of this study was to assess whether there are different patterns (classes) of joint health in young boys with severe haemophilia A (SHA) prescribed primary tailored prophylaxis. We also assessed whether age at first index joint bleed, blood group, FVIII gene abnormality variant, factor VIII trough level, first-year bleeding rate and adherence to the prescribed prophylaxis regimen significantly predicted joint damage trajectory, and thus class membership.

Methods: Using data collected prospectively as part of the Canadian Hemophilia Primary Prophylaxis Study (CHPS), we implemented a latent class growth mixture model technique to determine how many joint damage classes existed within the cohort.

Detectable Unmetabolized Folic Acid and Elevated Folate Concentrations in Folic Acid-Supplemented Canadian Children With Sickle Cell Disease.

Sickle cell disease (SCD) is an inherited hemoglobinopathy caused by a variant (rs344) in the gene encoding the β-globin subunit of hemoglobin. Chronic hemolytic anemia and increased erythropoiesis and RBC turnover in individuals with SCD can result in increased needs for folate and other B-vitamins. We assessed B-vitamin status, and the distribution of folate forms, including unmetabolized folic acid (UMFA), in Canadian children with SCD supplemented with 1 mg/d folic acid (current routine practice).

Positive effects of ultrasound-guided peripheral IV insertion on pediatric sickle cell anemia/thalassemia patients receiving automated red cell exchange procedures or chronic transfusion therapy.

Background: Peripheral vascular access and venipuncture are major causes of distress and anxiety for children and their parents. This is especially difficult for patients with hemoglobinopathies (thalassemia major and sickle cell disease) who require chronic blood transfusions. These patients require peripheral venous access for regular blood transfusions and (in the case of sickle cell disease) for automated red cell exchange procedures.

Folic acid supplementation in children with sickle cell disease: study protocol for a double-blind randomized cross-over trial.

Background: Sickle cell disease (SCD) is a genetic disorder which causes dysfunctional red blood cells (RBC) and is thought to increase requirements for folate, an essential B vitamin, due to increased RBC production and turnover in the disease. High-dose supplementation with 1-5 mg/d folic acid, synthetic folate, has been the standard recommendation for children with SCD. There is concern about whether children with SCD need such high doses of folic acid, following mandatory folic acid fortification of enriched grains in Canada, and advancements in medical therapies which extend the average lifespan of RBCs.

Outcomes indicators and processes in transitional care in adolescents with haemophilia: A Delphi survey of Canadian haemophilia care providers.

Introduction: It is unclear which outcome indicators should be used to measure the success of haemophilia transition programs, and what are key elements of a haemophilia transition program to ensure success.

Aim: To establish by expert consensus a list of important and feasible outcome indicators of successful haemophilia transition, and a list of key elements of transition planning.

Methods: A modified two-stage Delphi survey was developed and disseminated among a panel of Canadian interdisciplinary haemophilia care providers.

Prevalence of Vitamin D Deficiency Varies Widely by Season in Canadian Children and Adolescents with Sickle Cell Disease.

Sickle cell disease (SCD) is an inherited disorder caused by a variant (334) in the β-globin gene encoding hemoglobin. Individuals with SCD are thought to be at risk of vitamin D deficiency. Our aim was to assess serum 25-hydroxyvitamin D (25OHD) concentrations, estimate deficiency prevalence, and investigate factors associated with 25OHD concentrations in children and adolescents with SCD attending BC Children's Hospital in Vancouver, Canada.

The clinical impact of copy number variants in inherited bone marrow failure syndromes.

Inherited bone marrow failure syndromes (IBMFSs) comprise a genetically heterogeneous group of diseases with hematopoietic failure and a wide array of physical malformations. Copy number variants (CNVs) were reported in some IBMFSs. It is unclear what impact CNVs play in patients evaluated for a suspected diagnosis of IBMFS.

Further Validation of the c.151+1G>T Mutation as Cause of Distal Hereditary Motor Neuropathy.

Distal hereditary motor neuropathies represent a group of rare genetic disorders characterized by progressive distal motor weakness without sensory loss. Their genetic heterogeneity is high and thus eligible for diagnostic whole exome sequencing. The authors report successful application of whole exome sequencing in diagnosing a second consanguineous family with distal hereditary motor neuropathy due to a homozygous c.

Generation and optimization of the self-administered pediatric bleeding questionnaire and its validation as a screening tool for von Willebrand disease.

Objective: Our objective was to generate, optimize, and validate a self-administered pediatric bleeding questionnaire (Self-PBQ) as a screening tool for von Willebrand disease (VWD) in children referred to the hematology clinic for the first time.

Study Design: The Self-PBQ was generated by combining the validated expert-administered PBQ and the International Society on Thrombosis and Hemostasis (ISTH) bleeding assessment tool (BAT). Medical terminology was translated into lay language requiring a grade 4 reading level.

Intra-arterial methylprednisolone for severe steroid refractory gastrointestinal graft-versus-host disease.

Acute graft versus host disease (GVHD) is a significant complication of bone marrow transplantation with approximately half of patients being refractory to steroids. There are numerous second-line systemic immunosuppressive treatments but the overall prognosis is poor and these therapies are associated with high mortality due to infection. An alternative approach to systemic treatment for GVHD is targeted delivery of immunosuppression.

Factor XIII deficiency management: a review of the literature.

Factor XIII (FXIII) deficiency is a rare congenital bleeding disorder estimated to affect 1 in 2 million live births. Treatment often involves prophylaxis with FXIII concentrate and is especially important in preventing intracranial hemorrhage (ICH) and maintaining pregnancy in women of childbearing age. The rarity of this condition and lack of good quality evidence has resulted in a literature largely based on case reports/case series.

Congenital thrombotic thrombocytopenic purpura (cTTP) with two novel mutations.

Congenital thrombotic thrombocytopenic purpura (cTTP) is a rare disorder of childhood that has clinical and laboratory similarities to other, more common conditions. Prompt recognition is required as delays in therapy are associated with significant morbidity and failure to treat may lead to death. While the principles of treatment have not changed, enormous progress in the genetic and molecular understanding has taken place.

In Utero diagnosis and management of a fetus with homozygous α-Thalassemia in the second trimester: a case report and literature review.

Alpha thalassemia with the absence of 4 α-globin genes leads to fetal hydrops and fetal death from anemia. Historically considered a lethal condition, optimal in utero management of homozygous α-thalassemia is unclear. A fetus of Filipino descent at 26 weeks gestation presented with ultrasound evidence of anemia.

Diagnosing platelet delta-storage pool disease in children by flow cytometry.

Bleeding problems are symptomatic of platelet delta-storage pool diseases (SPDs) such as Hermansky-Pudlak syndrome. Although at present no cure is available for delta-SPD, early diagnosis is of great importance for prophylactic and supportive treatment. This study tested the usefulness of a flow cytometric assay for platelet serotonin in children.

Severe FVII deficiency caused by a new point mutation combined with a previously undetected gene deletion.

A 3-week-old Caucasian female presented with severe unprovoked parenchymal cerebral haemorrhage. Her plasma factor VII (FVII) activity was <0.01 units/ml.

Utility of anti-xa monitoring in children receiving enoxaparin for therapeutic anticoagulation.

Although enoxaparin is used to treat thromboembolism in children, current treatment guidelines are largely extrapolated from adults. The objectives of this study were to determine: i) correlation between enoxaparin dose and anti-factor Xa (anti-Xa) level, ii) intra-patient variability, and iii) whether dose or anti-Xa level is a predictor of outcomes. A retrospective chart review was conducted on all hospitalized patients receiving enoxaparin in a tertiary care pediatric institution.

Hyperuricemia and reticulocytopenia in association with autoimmune hemolytic anemia in two children.

Hyperuricemia developed in 2 children with autoimmune hemolytic anemia with reticulocytopenia at a time of hemolytic crisis. One likely cause of hyperuricemia is the destruction of nucleated RBC precursors by autoantibodies. It is advised that patients with autoimmune hemolytic anemia with reticulocytopenia be examined for hyperuricemia.

An assessment of published pediatric dosage guidelines for enoxaparin: a retrospective review.

Objective: To evaluate the ability of published dosage guidelines for enoxaparin to achieve therapeutic anticoagulation and to determine whether the routine monitoring of anti-Xa levels is still necessary at a tertiary care pediatric institution.

Methods: Consecutive charts and laboratory records were reviewed for all patients receiving treatment doses of enoxaparin for thrombosis in the authors institution over a 4-year period (1998-2002).

Results: Sixty-six percent (25/38) of the anti-Xa levels were within the recommended therapeutic range (0.

Beta-thalassemia in association with a new delta-chain hemoglobin variant [delta116(g18)Arg-->Leu]: implications for carrier screening and prenatal diagnosis.

We describe a complicated genetic counseling and prenatal diagnostic case involving an East Indian couple that had lost two consecutive pregnancies. Hemoglobinopathy screening was conducted to investigate the possibility of Hb Bart's hydrops fetalis or Hb H hydrops fetalis. The initial work-up indicated that alpha-thalassemia was not a contributing factor, with both parents being carriers of single gene deletions (-alpha(3.

Metastatic testicular rhabdomyosarcoma--a report of two cases.

Rhabdomyosarcoma is the most common type of soft tissue sarcoma in children. The tumor spreads by local extension, to regional lymph nodes, or by distant metastases. Metastatic spread to the testicle has been rarely described.