Shannon L. Carpenter

Evaluation for bleeding disorders in suspected child abuse

Bruising or bleeding in a child can raise the concern for child abuse. Assessing whether the findings are the result of trauma and/or whether the child has a bleeding disorder is critical. Many bleeding disorders are rare, and not every child with bruising/bleeding concerning for abuse requires an evaluation for bleeding disorders. In some instances, however, bleeding disorders can present in a manner similar to child abuse. The history and clinical evaluation can be used to determine the necessity of an evaluation for a possible bleeding disorder, and prevalence and known clinical presentations of individual bleeding disorders can be used to guide the extent of the laboratory testing. This clinical report provides guidance to pediatricians and other clinicians regarding the evaluation for bleeding disorders when child abuse is suspected.

Increased prevalence of inhibitors in Hispanic patients with severe haemophilia A enrolled in the Universal Data Collection database

Summary. Neutralizing inhibitors develop in 20–30% of patients with severe factor VIII (FVIII) deficiency. It is well established that Blacks have a higher prevalence of inhibitors than Whites. This is the first study to definitively demonstrate increased inhibitor prevalence in the Hispanic population. We compared inhibitor prevalence among various racial and ethnic groups in a cross‐sectional analysis of 5651 males with severe haemophilia A that participated in the Universal Data Collection project sponsored by the Centers for Disease Control and Prevention. We used logistic regression analysis to control for potential confounding variables. We assigned as Hispanic those participants who were white and labelled themselves Hispanic. The prevalence of high‐titre inhibitors in the Hispanic participants was 24.5% compared to 16.4% for White non‐Hispanic patients (OR 1.4, 95% CI 1.1, 1.7). Possibilities as to the underlying cause of increased inhibitor prevalence in minority ethnic populations include polymorphisms in the FVIII molecule, HLA subtypes and differing inflammatory responses. A better understanding may lead to tailored treatment programmes, or other therapies, to decrease or prevent inhibitor development.

Evaluating for Suspected Child Abuse: Conditions That Predispose to Bleeding

Child abuse might be suspected when children present with cutaneous bruising, intracranial hemorrhage, or other manifestations of bleeding. In these cases, it is necessary to consider medical conditions that predispose to easy bleeding/bruising. When evaluating for the possibility of bleeding disorders and other conditions that predispose to hemorrhage, the pediatrician must consider the child’s presenting history, medical history, and physical examination findings before initiating a laboratory investigation. Many medical conditions can predispose to easy bleeding. Before ordering laboratory tests for a disease, it is useful to understand the biochemical basis and clinical presentation of the disorder, condition prevalence, and test characteristics. This technical report reviews the major medical conditions that predispose to bruising/bleeding and should be considered when evaluating for abusive injury.

AKI in Children Hospitalized with Nephrotic Syndrome

BACKGROUND AND OBJECTIVES Children with nephrotic syndrome can develop life-threatening complications, including infection and thrombosis. While AKI is associated with adverse outcomes in hospitalized children, little is known about the epidemiology of AKI in children with nephrotic syndrome. The main objectives of this study were to determine the incidence, epidemiology, and hospital outcomes associated with AKI in a modern cohort of children hospitalized with nephrotic syndrome. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Records of children with nephrotic syndrome admitted to 17 pediatric nephrology centers across North America from 2010 to 2012 were reviewed. AKI was classified using the pediatric RIFLE definition. RESULTS AKI occurred in 58.6% of 336 children and 50.9% of 615 hospitalizations (27.3% in stage R, 17.2% in stage I, and 6.3% in stage F). After adjustment for race, sex, age at admission, and clinical diagnosis, infection (odds ratio, 2.24; 95% confidence interval, 1.37 to 3.65; P=0.001), nephrotoxic medication exposure (odds ratio, 1.35; 95% confidence interval, 1.11 to 1.64; P=0.002), days of nephrotoxic medication exposure (odds ratio, 1.10; 95% confidence interval, 1.05 to 1.15; P<0.001), and intensity of medication exposure (odds ratio, 1.34; 95% confidence interval, 1.09 to 1.65; P=0.01) remained significantly associated with AKI in children with nephrotic syndrome. Nephrotoxic medication exposure was common in this population, and each additional nephrotoxic medication received during a hospitalization was associated with 38% higher risk of AKI. AKI was associated with longer hospital stay after adjustment for race, sex, age at admission, clinical diagnosis, and infection (difference, 0.45 [log]days; 95% confidence interval, 0.36 to 0.53 [log]days; P<0.001). CONCLUSIONS AKI is common in children hospitalized with nephrotic syndrome and should be deemed the third major complication of nephrotic syndrome in children in addition to infection and venous thromboembolism. Risk factors for AKI include steroid-resistant nephrotic syndrome, infection, and nephrotoxic medication exposure. Children with AKI have longer hospital lengths of stay and increased need for intensive care unit admission.

Current prescription of prophylactic factor infusions and perceived adherence for children and adolescents with haemophilia: a survey of haemophilia healthcare professionals in the United States.

Summary.  The primary goal of prophylaxis in patients with severe haemophilia is to convert the phenotype from severe to moderate and to prevent the development of chronic arthropathy. Prior studies have demonstrated that prophylaxis decreases episodes of joint bleeds and chronic arthropathy. Effectiveness depends on prescription of prophylaxis and adherence to the prescribed regimen. The aim of this study was to determine if prescription of prophylaxis for children with haemophilia and perceptions of adherence to prophylaxis have changed since publication of the Joint Outcome Study (JOS). A questionnaire was sent, in electronic and written formats, to health professionals who provide care to children with haemophilia at US haemophilia treatment centres (HTCs). The response rate was 56 of 128 (44%) of the targeted HTCs. There were a few missing data and denominators are provided. All responses agreed with the results of the JOS and 30/55 (55%) reported the JOS increased their prescription of prophylaxis. Nineteen of 56 (34%) physicians or HTC staff reported that they had not prescribed prophylaxis within the last year due to concerns about adherence, and 19/56 (34%) reported they had stopped prophylaxis due to concerns about adherence within the last year. Predicted adherence decreased with increasing age. Prescription of prophylaxis appears to be increasing since publication of the JOS. Strategies to improve adherence may increase the likelihood of physician prescription of prophylaxis and make prophylaxis easier to implement for individual patients, thereby improving the clinical outcome of children and adults with haemophilia.

Inhibitor recurrence after immune tolerance induction: a multicenter retrospective cohort study.

Immune tolerance induction (ITI) in patients with congenital hemophilia A is successful in up to 70%. Although there is growing understanding of predictors of response to ITI, the probability and predictors of inhibitor recurrence after successful ITI are not well understood.

Menstrual Patterns and Treatment of Heavy Menstrual Bleeding in Adolescents with Bleeding Disorders.

STUDY OBJECTIVE To characterize menstrual bleeding patterns and treatment of heavy menstrual bleeding in adolescents with bleeding disorders. DESIGN, SETTING, AND PARTICIPANTS We conducted a retrospective review of female patients aged nine to 21 years with known bleeding disorders who attended a pediatric gynecology, hematology, and comprehensive hematology/gynecology clinic at a childrens hospital in a metropolitan area. MAIN OUTCOME MEASURES Prevalence of heavy menstrual bleeding at menarche, prolonged menses, and irregular menses among girls with bleeding disorders and patterns of initial and subsequent treatment for heavy menstrual bleeding in girls with bleeding disorders. RESULTS Of 115 participants aged nine to 21 years with known bleeding disorders, 102 were included in the final analysis. Of the 69 postmenarcheal girls, almost half (32/69, 46.4%) noted heavy menstrual bleeding at menarche. Girls with von Willebrand disease were more likely to have menses lasting longer than seven days. Only 28% of girls had discussed a treatment plan for heavy menstrual bleeding before menarche. Hormonal therapy was most commonly used as initial treatment of heavy menstrual bleeding. Half (53%) of the girls failed initial treatment. Combination (hormonal and non-hormonal therapy) was more frequently used for subsequent treatment. CONCLUSIONS Adolescents with bleeding disorders are at risk of heavy bleeding at and after menarche. Consultation with a pediatric gynecologist and/or hematologist prior to menarche may be helpful to outline abnormal patterns of menstrual bleeding and to discuss options of treatment in the event of heavy menstrual bleeding.

Common Acquired Causes of Thrombosis in Children

Compared to adults, venous thromboembolism in the pediatric population is a rare event. Cancer, cardiac disease, antiphospholipid antibodies, and indwelling catheters are established risk factors for thromboembolism in children. We examined the literature related to thrombophilia in children, childhood cancer and thrombosis, cardiac disease and thrombosis, and antiphospholipid antibody syndrome in children. Citations in identified articles yielded additional articles for review. We found that studies of acquired thrombophilia in children are limited. Current treatment for thromboembolism in children is based on adult data therefore optimal treatment in this population remains unclear.

Clinical variables and Staphylococcus aureus virulence factors associated with venous thromboembolism in children

OBJECTIVES Children with Staphylococcus aureus (SA) bacteremia risk developing venous thromboembolism (VTE). We sought to identify clinical variables and bacterial virulence factors associated with VTE in SA bacteremia. STUDY DESIGN This is a single-institution retrospective study of 229 children with SA bacteremia hospitalized from 2005 to 2008. Clinical data were abstracted from patient charts. Two-hundred three SA isolates were analyzed by polymerase chain reaction. The Pediatric Health Information System (PHIS) database was queried to identify subjects with a central venous line (CVL) or complex chronic conditions (CCC). Logistic regression analysis was employed to determine which factors most greatly influenced VTE. RESULTS VTE was present in 9.2% (n=21/229). Superficial thrombi were excluded. Mortality was greater in patients with VTE [24% vs. 6% (p=0.016)]. Among SA isolates available for virulence testing, the majority (70%; n=139) were methicillin-sensitive SA (MSSA). Methicillin-resistant SA (MRSA) infection was associated with VTE (p=0.01). The most common sites of thrombosis were extremity deep vein (58%; n=14/24), head/neck (29%; n=7), and visceral (13%; n=3). One subject had a pulmonary embolism. The presence of a CVL or a CCC was not associated with VTE. Independent predictors of VTE were C-reactive protein (CRP)≥20mg/dl [OR 4.2, 95% CI 1.16-15.25] and hemoglobin nadir ≤9g/dl [OR 5.2, 95% CI 1.3-20.64]. CONCLUSIONS In addition to MRSA infection, CRP≥20mg/dl and hemoglobin nadir ≤9g/dl were associated with VTE in SA bacteremia. These factors may serve as markers for increased risk of VTE with invasive SA disease.

Bruising in Children Practice Patterns of Pediatric Hematologists and Child Abuse Pediatricians

The evaluation for children with bruising may be affected by the specialty to which they are referred. We conducted a 3-year retrospective review of subjects referred for bruising to Child Abuse Pediatrics (CAP) or Pediatric Hematology to identify characteristics associated with referral to each specialty and to compare the diagnostic evaluations and diagnoses based on specialty. Of 369 subjects, 275 were referred to CAP and 94 to Hematology. Clinical exam findings were similar in both groups. Hematology referrals were significantly more likely to have laboratory evaluations. Among those referred to CAP, 9.5% had head computed tomography scans and 27.3% had skeletal surveys. No children referred to Hematology had these imaging studies performed. Hematology never diagnosed child physical abuse, and CAP never diagnosed bleeding disorders. Pediatric hematologists and CAPs perform different evaluations and reach different diagnostic conclusions for similar patients with bruising. Further investigation of these practice patterns is warranted.