Barriers to and Facilitators of Iron Therapy in Children with Iron Deficiency Anemia.

OBJECTIVE: To characterize barriers to and facilitators of successful iron therapy in young children with iron deficiency anemia (IDA) from an in-depth parental perspective. STUDY DESIGN: Prospective, mixed methods study of children age 9 months to 4 years with a diagnosis of nutritional IDA by clinical history and laboratory criteria and their parents. Clinical data were obtained from the electronic health record. Semistructured interviews focused on knowledge of IDA, clinical effects, experience with iron therapies, and motivation were conducted with the parent who identified as the child's primary caregiver. RESULTS: Twenty patient-parent dyads completed the study; 80% (n = 16) identified as Hispanic/Latino (white). Patients' median age was 23 months (50% male); median initial hemoglobin concentration was 8.2 g/dL and duration of oral iron therapy was 3 months. Parents' median age was 29 years (85% female); 8 interviews (40%) were conducted in Spanish. Barriers included difficulty in administering oral iron owing to side effects and poor taste. Facilitators included provision of specific instructions; support from healthcare providers and additional caregivers at home; motivation to benefit child's health, which was strengthened by strong emotional reactions (ie, stress, anxiety) to therapy and follow-up; and an appreciation of child's improvement with successful completion of therapy. CONCLUSIONS: Our findings support the need for interventions designed to promote oral iron adherence in children with IDA. Rather than focusing on knowledge content related to IDA, interventions should aim to increase parental motivation by emphasizing the health benefits of adhering to iron therapy and avoiding more invasive interventions.

Barriers and facilitators of risk-based health care for adult survivors of childhood cancer: A report from the Childhood Cancer Survivor Study.

BACKGROUND: Optimal risk-based survivor health care includes surveillance for late effects and education targeted at reducing or preventing risky health behaviors. Understanding the reasons for a lack of risk-based follow-up care is essential. METHODS: Adult participants from the Childhood Cancer Survivor Study were surveyed about having a cancer-related visit in the past 2 years and the likelihood of having a cancer-related visit in the future. Additional factors thought to be related to the primary outcomes were also assessed. RESULTS: Nine hundred seventy-five survivors completed the survey. Twenty-seven percent (95% confidence interval [CI], 24%-30%) had a cancer-related medical visit in the previous 2 years, and 41% (95% CI, 38%-44%) planned to have such a visit within the next 2 years. The likelihood of having had a cancer-related visit within the last 2 years was higher among survivors assigning greater importance to these visits (relative risk [RR], 1.2; 95% CI, 1.1-1.3), perceiving greater susceptibility to health problems (RR, 1.2; 95% CI, 1.1-1.3), having a moderate to life-threatening chronic health problem related to their cancer (RR, 2.1; 95% CI, 1.7-2.7), seeing a primary care provider for a cancer-related problem (RR, 1.3; 95% CI, 1.0-1.6), having a cancer treatment summary (RR, 1.3; 95% CI, 1.0-1.6), and endorsing greater confidence in physicians' abilities to address questions and concerns (RR, 1.2; 95% CI, 1.0-1.3). CONCLUSIONS: Educational interventions improving awareness of treatment history and susceptibility to cancer-related late effects and corresponding risk-based care are likely to be beneficial for survivors of childhood cancers.

Factor VIII prophylaxis effects outweigh other hemostasis contributors in predicting severe haemophilia A joint outcomes.

INTRODUCTION: The Joint Outcome Study (JOS) demonstrated that previously untreated children with severe haemophilia A treated with prophylactic factor VIII (FVIII) concentrate had superior joint outcomes at age 6 years compared to those children treated episodically for bleeding. However, variation in joint outcome within each treatment arm was not well explained. AIM: In this study, we sought to better understand variation in joint outcomes at age 6 years in participants of the JOS. METHODS: We evaluated the influence of FVIII half-life, treatment adherence, constitutional coagulant and anticoagulant proteins, and global assays on joint outcomes (number of joint bleeds, total number of bleeds, total MRI score and joint physical exam score). Logistic regression was used to evaluate the association of variables with joint failure status on MRI, defined as presence of subchondral cyst, surface erosion or joint-space narrowing. Each parameter was also correlated with each joint outcome using Spearman correlations. RESULTS: Prophylaxis treatment arm and FVIII trough were each found to reduce risk of joint failure on univariate logistic regression analysis. When controlling for treatment arm, FVIII trough was no longer significant, likely because of the high level of covariation between these variables. We found no consistent correlation between any laboratory assay performed and any joint outcome parameter measured. CONCLUSION: In the JOS, the effect of prescribed prophylactic FVIII infusions on joint outcome overshadowed the contribution of treatment adherence, FVIII half-life, global assays of coagulation and constitutional coagulation proteins. (ClinicalTrials.gov number, NCT00207597).

Second-line treatments in children with immune thrombocytopenia: Effect on platelet count and patient-centered outcomes.

Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder with isolated thrombocytopenia and hemorrhagic risk. While many children with ITP can be safely observed, treatments are often needed for various reasons, including to decrease bleeding, or to improve health related quality of life (HRQoL). There are a number of available second-line treatments, including rituximab, thrombopoietin-receptor agonists, oral immunosuppressive agents, and splenectomy, but data comparing treatment outcomes are lacking. ICON1 is a prospective, multi-center, observational study of 120 children starting second-line treatments for ITP designed to compare treatment outcomes including platelet count, bleeding, and HRQoL utilizing the Kids ITP Tool (KIT). While all treatments resulted in increased platelet counts, romiplostim had the most pronounced effect at 6 months (P = .04). Only patients on romiplostim and rituximab had a significant reduction in both skin-related (84% to 48%, P = .01 and 81% to 43%, P = .004) and non-skin-related bleeding symptoms (58% to 14%, P = .0001 and 54% to 17%, P = .0006) after 1 month of treatment. HRQoL significantly improved on all treatments. However, only patients treated with eltrombopag had a median improvement in KIT scores at 1 month that met the minimal important difference (MID). Bleeding, platelet count, and HRQoL improved in each treatment group, but the extent and timing of the effect varied among treatments. These results are hypothesis generating and help to improve our understanding of the effect of each treatment on specific patient outcomes. Combined with future randomized trials, these findings will help clinicians select the optimal second-line treatment for an individual child with ITP.

Disorders of Iron Metabolism: New Diagnostic and Treatment Approaches to Iron Deficiency.

Iron deficiency anemia is the leading cause of anemia worldwide and affects many young children and adolescent girls in the United States. Its signs and symptoms are subtle despite significant clinical effects. Iron deficiency anemia is diagnosed clinically by the presence of risk factors and microcytic anemia. Improvement following a trial of oral iron therapy is confirmative. An array of iron laboratory tests is available with variable indications. Clinical trial and iron absorption data support a shift to lower-dose oral iron therapy. Intravenous iron should be considered in children who fail oral iron or who have more complex disorders.

Predictors of remission in children with newly diagnosed immune thrombocytopenia: Data from the Intercontinental Cooperative ITP Study Group Registry II participants.

BACKGROUND: Immune thrombocytopenia (ITP) during childhood spontaneously remits in up to 80% of children. Predictors of remission are not well understood. PROCEDURE: We analyzed data from Intercontinental Cooperative ITP Study Group (ICIS) Registry II, a large prospective cohort of children with ITP, to investigate factors that might predict remission. RESULTS: In ICIS Registry II, 705 patients had data collected through 12 months following diagnosis, with 383 patients having data available at 24 months as well. Younger age and pharmacologic treatment at diagnosis were significantly associated with disease resolution at 12 and 24 months (P < 0.0001 for both) as was bleeding at diagnosis (P < 0.0001 and P = 0.0213, respectively). Gender and platelet count at diagnosis were not significantly correlated with remission. In the multivariable analysis, remission at 12 months was associated with younger age, higher bleeding grade at diagnosis, and treatment with a combination of intravenous immunoglobulin (IVIG) and corticosteroids at diagnosis. Only younger age and treatment with IVIG and steroids in combination at diagnosis were associated with remission at 24 months. Patients <1 year of age had the highest odds of achieving remission at both 12 months (OR 4.7, 95% CI: 2.0-10.6) and 24 months (OR 7.0, 95% CI: 2.3-20.8). CONCLUSIONS: Younger age, bleeding severity at diagnosis, and initial treatment with a combination of corticosteroids and IVIG are associated with remission at 12 months in the ICIS Registry II. Patients <1 year of age have the highest likelihood of remission. The relationship of bleeding and treatment at diagnosis requires further study to clarify whether these are independent predictors of remission.

Effect of Low-Dose Ferrous Sulfate vs Iron Polysaccharide Complex on Hemoglobin Concentration in Young Children With Nutritional Iron-Deficiency Anemia: A Randomized Clinical Trial.

Importance: Iron-deficiency anemia (IDA) affects millions of persons worldwide, and is associated with impaired neurodevelopment in infants and children. Ferrous sulfate is the most commonly prescribed oral iron despite iron polysaccharide complex possibly being better tolerated. Objective: To compare the effect of ferrous sulfate with iron polysaccharide complex on hemoglobin concentration in infants and children with nutritional IDA. Design, Setting, and Participants: Double-blind, superiority randomized clinical trial of infants and children aged 9 to 48 months with nutritional IDA (assessed by history and laboratory criteria) that was conducted in an outpatient hematology clinic at a US tertiary care hospital from September 2013 through November 2015; 12-week follow-up ended in January 2016. Interventions: Three mg/kg of elemental iron once daily as either ferrous sulfate drops or iron polysaccharide complex drops for 12 weeks. Main Outcomes and Measures: Primary outcome was change in hemoglobin over 12 weeks. Secondary outcomes included complete resolution of IDA (defined as hemoglobin concentration >11 g/dL, mean corpuscular volume >70 fL, reticulocyte hemoglobin equivalent >25 pg, serum ferritin level >15 ng/mL, and total iron-binding capacity <425 µg/dL at the 12-week visit), changes in serum ferritin level and total iron-binding capacity, adverse effects. Results: Of 80 randomized infants and children (median age, 22 months; 55% male; 61% Hispanic white; 40 per group), 59 completed the trial (28 [70%] in ferrous sulfate group; 31 [78%] in iron polysaccharide complex group). From baseline to 12 weeks, mean hemoglobin increased from 7.9 to 11.9 g/dL (ferrous sulfate group) vs 7.7 to 11.1 g/dL (iron complex group), a greater difference of 1.0 g/dL (95% CI, 0.4 to 1.6 g/dL; P < .001) with ferrous sulfate (based on a linear mixed model). Proportion with a complete resolution of IDA was higher in the ferrous sulfate group (29% vs 6%; P = .04). Median serum ferritin level increased from 3.0 to 15.6 ng/mL (ferrous sulfate) vs 2.0 to 7.5 ng/mL (iron complex) over 12 weeks, a greater difference of 10.2 ng/mL (95% CI, 6.2 to 14.1 ng/mL; P < .001) with ferrous sulfate. Mean total iron-binding capacity decreased from 501 to 389 µg/dL (ferrous sulfate) vs 506 to 417 µg/dL (iron complex) (a greater difference of -50 µg/dL [95% CI, -86 to -14 µg/dL] with ferrous sulfate; P < .001). There were more reports of diarrhea in the iron complex group than in the ferrous sulfate group (58% vs 35%, respectively; P = .04). Conclusions and Relevance: Among infants and children aged 9 to 48 months with nutritional iron-deficiency anemia, ferrous sulfate compared with iron polysaccharide complex resulted in a greater increase in hemoglobin concentration at 12 weeks. Once daily, low-dose ferrous sulfate should be considered for children with nutritional iron-deficiency anemia. Trial Registration: clinicaltrials.gov Identifier: NCT01904864.

Patterns and influences in health-related quality of life in children with immune thrombocytopenia: A study from the Dallas ITP Cohort.

BACKGROUND: Relationships between clinical/demographic factors and health-related quality of life (HRQoL) in childhood immune thrombocytopenia (ITP) remain poorly understood. Recent studies reveal conflicting information about factors that contribute to HRQoL. METHODS: This was a prospective, single-institution, cohort study of newly diagnosed children with ITP. Serial evaluations of HRQoL were performed using the Kid's ITP Tools (KIT), scored from 0 (worst) to 100 (best), at enrollment and 1 week, 6 months, and 12 months following diagnosis. All visits included bleeding severity grading. Relationships between HRQoL and platelet count, treatment, bleeding severity, and course of disease were examined. RESULTS: A total of 99 children with newly diagnosed ITP were evaluable for analysis. KIT scores were low at diagnosis for parents (median 26, range 15-43) and children (median 65, range 55-81) and were not influenced by age or platelet count. At diagnosis, children who received treatment had lower platelet counts (P = 0.005), more severe hemorrhage (P < 0.0125), and lower HRQoL by parent, child, and proxy reporting (P < 0.05). Oral bleeding negatively impacted proxy-reported disease burden at diagnosis (P = 0.01). Persistence of disease and lower platelet counts at 6 and 12 month visits were the only factors noted to consistently impact quality of life beyond diagnosis for both parents and children. CONCLUSIONS: HRQoL is low at diagnosis but significantly improves over time. Patients with ongoing disease and lower platelet counts continue to have significant disease burden.

Iron Deficiency Anemia in Adolescents Who Present with Heavy Menstrual Bleeding.

STUDY OBJECTIVE: To assess the clinical severity and initial treatment of iron deficiency anemia (IDA) in female adolescents with heavy menstrual bleeding (HMB) in our center. DESIGN: Retrospective cohort study of electronic medical records via search of administrative records using International Classification of Diseases Ninth Revision codes for IDA or unspecified anemia and disorders of menstruation. SETTING: Children's Medical Center in Dallas, Texas. PARTICIPANTS: One hundred seven patients with HMB and concomitant IDA (median age, 14.4 years) who presented to the outpatient, emergency department, and/or inpatient settings. RESULTS: The median initial hemoglobin concentration for all patients (n = 107) was 7.4 g/dL, and most (74%, n = 79) presented to the emergency department or via inpatient transfer. Symptomatic IDA was treated with blood transfusion in 46 (43%, n = 46). Ferrous sulfate was the most commonly prescribed oral iron therapy. Seven patients received intravenous iron therapy either initially or after oral iron treatment failure. Combined oral contraceptives were commonly prescribed for abnormal uterine bleeding, yet 10% of patients (n = 11) received no hormonal therapy during their initial management. Evaluation for underlying bleeding disorders was inconsistent. CONCLUSION: Severe anemia because of IDA and HMB resulting in urgent medical care, including hospitalization and blood transfusion, is a common but underemphasized problem in adolescent girls. In addition to prevention and early diagnosis, meaningful efforts to improve initial management of adolescents with severe HMB and IDA are necessary.

Intravenous Ferric Carboxymaltose in Children with Iron Deficiency Anemia Who Respond Poorly to Oral Iron.

OBJECTIVE: To assess the benefits and risks of intravenous (IV) ferric carboxymaltose (FCM) in children with iron deficiency anemia (IDA). STUDY DESIGN: In a retrospective cohort study of patients seen at our center, we identified all FCM infusions in children with IDA over a 12-month period through a query of pharmacy records. Clinical data, including hematologic response and adverse effects, were extracted from the electronic medical record. RESULTS: A total of 116 IV FCM infusions were administered to 72 patients with IDA refractory to oral iron treatment (median age, 13.7 years; range, 9 months to 18 years). Median preinfusion and postinfusion hemoglobin values were 9.1 g/dL and 12.3 g/dL, respectively (at 4-12 weeks after the initial infusion; n = 53). Sixty-five patients (84%) experienced no adverse effects. Minor transient complications were encountered during or immediately after 7 infusions. CONCLUSION: FCM administered as a short IV infusion without a test dose proved to be safe and highly effective in a small yet diverse population of infants, children, and adolescents with IDA refractory to oral iron therapy.

Deficiencies in the Management of Iron Deficiency Anemia During Childhood.

Limited high-quality evidence supports the management of iron deficiency anemia (IDA). To assess our institutional performance in this area, we retrospectively reviewed IDA treatment practices in 195 consecutive children referred to our center from 2006 to mid-2010. The majority of children were ≤4 years old (64%) and had nutritional IDA (74%). In 11- to 18-year-old patients (31%), the primary etiology was menorrhagia (42%). Many were referred directly to the emergency department and/or prescribed iron doses outside the recommended range. Poor medication adherence and being lost-to-follow-up were common. Substantial improvements are required in the management of IDA.

Sports Participation in Children and Adolescents with Immune Thrombocytopenia (ITP).

We surveyed 278 pediatric hematologists/oncologists regarding how children with immune thrombocytopenia (ITP) are counseled for participation in sports. Results show substantial variation in physician perception of contact risk for different sports, and the advice offered about restriction of sport activities of affected children. Many physicians recommend restriction of sports when platelet counts are under 50 × 10(9) /L. Such restriction may affect the child's quality of life despite their having an overall benign disease.

Management of iron deficiency anemia: a survey of pediatric hematology/oncology specialists.

BACKGROUND: Iron deficiency anemia (IDA) is the most common hematologic condition in children and adolescents in the United States (US). No prior reports have described the management of IDA by a large cohort of pediatric hematology/oncology specialists. PROCEDURE: A 20-question electronic survey that solicited responses to two hypothetical cases of IDA was sent to active members of the American Society of Pediatric Hematology/Oncology (ASPHO) in the US. RESULTS: Of 1,217 recipients, 398 (32.7%) reported regularly treating IDA and completed the survey. In a toddler with nutritional IDA, 15% (N = 61) of respondents reported ordering no diagnostic test beyond a complete blood count. Otherwise, wide variability in laboratory testing was reported. For treatment, most respondents would prescribe ferrous sulfate (N = 335, 84%) dosed at 6 mg/kg/day (N = 248, 62%) divided twice daily (N = 272, 68%). The recommended duration of iron treatment after resolution of anemia and normalized serum ferritin varied widely from 0 to 3 months. For an adolescent with heavy menstrual bleeding and IDA, most respondents recommended ferrous sulfate (N = 327, 83%), with dosing based on the number of tablets daily. For IDA refractory to oral treatment, intravenous iron therapy was recommended most frequently, 48% (N = 188) using iron sucrose, 17% (N = 68) ferric gluconate, and 15% (N = 60) low molecular weight iron dextran. CONCLUSION: The approach to diagnosis and treatment of IDA in childhood was widely variable among responding ASPHO members. Given the lack of an evidence base to guide clinical decision making, further research investigating IDA management is needed.

Long-term use of the thrombopoietin-mimetic romiplostim in children with severe chronic immune thrombocytopenia (ITP).

BACKGROUND: Treatment of chronic severe pediatric ITP is not well studied. In a phase 1/2 12-16-week study, 15/17 romiplostim-treated patients achieved platelet counts ≥50 × 109 /L, and romiplostim treatment was well tolerated. In a subsequent open-label extension (≤109 weeks), 20/22 patients received romiplostim; all achieved platelet counts >50 × 109 /L. Twelve patients continued in a second extension (≤127 weeks). Longitudinal data from start of romiplostim treatment through the two extensions were evaluated to investigate the safety and efficacy of long-term romiplostim treatment in chronic severe pediatric ITP. PROCEDURE: Patients received weekly subcutaneous romiplostim, adjusted by 1 µg/kg/week to maintain platelet counts (50-200 × 109 /L, maximum dose 10 µg/kg). Bone marrow examinations were not required. RESULTS: At baseline, patients were median age 10.0 years; median ITP duration 2.4 years; median platelet count 13 × 109 /L; 73% were male; and 36% had prior splenectomy. Median romiplostim treatment duration was 167 weeks (Q1, Q3: 78,227 weeks), and median average weekly dose was 5.4 µg/kg (Q1, Q3: 4.3, 8.0 µg/kg). Seven patients discontinued treatment: four withdrew consent, two were noncompliant, and one received alternative therapy. None withdrew because of adverse events (AEs). After the first 12 weeks, median platelet counts remained >50 × 109 /L. Eight (36.4%) patients received rescue medication, and 14 (63.6%) used concurrent ITP therapy. Seven patients (31.8%) reported serious AEs, and two (9.1%) reported life-threatening AEs (both thrombocytopenia); there were no serious AEs attributed to treatment and no fatalities. CONCLUSIONS: Long-term romiplostim treatment in this small cohort increased and maintained platelet counts for over 4 years in children with ITP with good tolerability and without significant toxicity. Pediatr Blood Cancer 2015;62:208-213. © 2014. The Authors. Pediatr Blood & Cancer published by Wiley Periodicals, Inc.

Immune thrombocytopenia and alopecia areata: spontaneous occurrence and resolution in the same patient.

Alopecia areata (AA) and immune thrombocytopenia (ITP) are autoimmune conditions occasionally encountered by pediatricians, but their simultaneous occurrence is rare. We describe here a 7-year-old female who acutely developed both AA and ITP. Within 3 months both conditions resolved spontaneously, suggesting a pathophysiologic relationship.

Diagnosis and management of iron deficiency anemia.

Iron deficiency anemia (IDA) is a common hematologic condition, affecting a substantial proportion of the world's women and young children. Optimal management of IDA requires an accurate diagnosis, identification and correction of the underlying cause, provision of medicinal iron therapy, and confirmation of treatment success. There are limited data to support current treatment approaches regarding oral iron preparation, dosing, monitoring, and duration of therapy. New intravenous iron agents have improved safety profiles, which may foster their increased utilization in the treatment of patients with IDA. Clinical trials focused on improving current treatment standards for IDA are sorely needed.