Pyruvate kinase (PK) deficiency is a rare, congenital red blood cell disorder caused by a single gene defect. The spectrum of genotypes, variants, and phenotypes are broad, commonly requiring a multimodal approach including enzyme and genetic testing for accurate and reliable diagnosis. Similarly, management of primary and secondary sequelae of PK deficiency varies, mainly including supportive care with transfusions and surgical interventions to improve symptoms and quality of life. Given the risk of acute and long-term complications of PK deficiency and its treatment, regular monitoring and management of iron burden and organ dysfunction is critical. Therefore, all children and adolescents with PK deficiency should receive regular hematology care with visits at least every 6 months regardless of transfusion status. We continue to learn more about the spectrum of symptoms and complications of PK deficiency and best practice for monitoring and management through registry efforts (NCT03481738).The treatment of PK deficiency has made strides over the last few years with newer disease-modifying therapies being developed and studied, with the potential to change the course of disease in childhood and beyond.
Introduction. Advances in medicine in the last four decades have allowed adolescents with Sickle Cell Disease (SCD) to survive into adulthood. Consequently, there is a sizeable number of maturing young adults with SCD who require transition from pediatric to adult care. This transition can be difficult given the tumultuousness of outgrowing adolescence and entering adulthood, the burden of living with a chronic disease, and the self-advocacy and medical independence expected from patients by adult health care providers. To better understand utilization of care during this period in a comprehensive SCD center, we investigated the number of patients who transferred and successfully transitioned from pediatric outpatient hematology care to adult care. Methods. Following IRB approval, a retrospective chart review of patients with SCD aged 18-23 years in the Duke University Medical Center electronic medical record database was conducted. Included for each patient was a list of all clinic encounters at Duke through the December 2013. A total of 342 SCD patient records were retrieved, of which 88 (26%) were excluded because of missing data on outpatient SCD encounters. Transfer was defined as a clinic visit in pediatrics followed by a subsequent visit in the adult clinic. Successful transition was defined as at least 1 year of follow up care in adult hematology clinic post-transfer. Results. The 284 patient records fell into three utilization patterns: 182 whose last encounter was a pediatric visit (72%), 20 who started care in the adult clinic (8%), and 52 who transferred from pediatric to adult care (20%). Within the pediatric group, 36 patients were actively receiving care while 146 were lost to follow-up. Among patients that transferred, the average age of transfer was 18.6 years and the transfer occurred within 3 months of the last pediatric visit for 61% of patients. Although 71% of transferred patients continued care for at least 1 year post-transfer, the majority of 19-20 year old patients (61%) did not transition successfully. Discussion. Our findings show that SCD patients aged 18-23 are having difficulty transferring and successfully transitioning from pediatric to adult hematology care in the Duke Medical Center despite having a single medicine-pediatric provider. The majority of patients had their last visit in pediatric care which is consistent with Duke’s SCD clinical practice to keep 18-20 year old patients in pediatric care to better educate patients. The large number of patients who stopped care in pediatrics may be explained by care provided by non-Duke hematologists or primary care providers; relocation; or use of acute care clinics (emergency department, urgent care, and day hospital) as a substitution for regular care. As observed in this data, when transfer does occur among this younger adult group of 18-20 year olds, only a third of the patients have a successful transition. The low success rate may be accounted for by patient impression of health; avoidance of regular care; loss of insurance; and struggle with independence. Implications. The results underscore the need to not only improve successful transition rates for SCD patients but also to assist and track patients preparing to transfer to adult specialty clinics. Further research is needed to determine what is happening to patients who are lost to follow-up during their pediatric care and to determine the relationship between the amount of time to transfer and successful transition rates. Because our robust definition of a successful transition is more sensitive to identifying gaps in continuous care as compared to other success metrics based on a 50% show rate, we were able to identify 19-20 years as a critical age group for intervention. Disclosures Shah: Novartis: Speakers Bureau.
Background: Acute chest syndrome (ACS) is a form of acute lung injury that is a leading cause of morbidity and mortality in children and adults with sickle cell disease (SCD). Despite advances in health maintenance and disease-modifying therapies for SCD, ACS remains a common and often severe complication. There is still limited understanding of why some patients suffer more severe ACS episodes. Few studies have specifically investigated clinical parameters associated with severe ACS in the pediatric population. The purpose of this study is to determine the association between hematologic and radiologic clinical findings and severe ACS in children and adolescents with SCD. Methods: We conducted a single-institution retrospective chart review of 120 pediatric patients with HbSS or HbSβ 0 thalassemia and at least one documented episode of ACS, and then further classified patients by their most severe ACS event. We extracted laboratory and radiologic data to compare clinical findings. Infections reported in patient encounters were verified by documented viral PCR and blood cultures. Continuous variables were analyzed using Welch's t-test; categorical variables were analyzed using Fisher's exact test. Results: Eighty patients in the moderate ACS group were excluded for this analysis. Twenty patients (median age 5.6 years, SD 4.20) had mild ACS defined by no supplemental oxygen requirement, only one segmental or lobar infiltrate on chest radiography, and transfusion of less than 3 units (or 15 cc/kg) of red blood cells. Twenty patients (median age 7.6 years, SD 4.01) had severe ACS characterized by acute respiratory failure requiring mechanical (invasive or non-invasive) ventilation and/or exchange transfusion. Median length of stay for patients with severe ACS was longer than for the mild cohort (mean: 8 days vs 2 days, p <0.001). The median absolute neutrophil count (ANC) was significantly higher in the severe ACS cohort (19.8 x 10 3µL vs. 9.4 x 10 3 µL, p = 0.004). The median platelet count nadir was significantly lower in the severe ACS group compared to the mild group (165 x 10 3 µL vs. 309 x 10 3 µL, p <0.001). Review of radiologic data showed that the median number of lobes affected in the severe ACS group were 3, compared to 1 lobe in the mild group (p <0.001). Approximately 65% of patients with mild ACS had left-sided disease (p = 0.18), while 85% of patients with severe ACS had bilateral disease (p = 0.002). The risk of pleural effusions was also significantly increased with severe ACS [OR 76.00 (95% CI 9.235-825.6), p <0.001]. When we analyzed infection at time of ACS, the proportion of laboratory-confirmed viral infections were twice as high in the mild ACS cohort (41.2%), compared to the severe ACS cohort (20.0%, p = 0.279). There were no bloodstream bacterial infections found in either cohort. Conclusion: Severe ACS in children is a clinically distinct phenotype associated with longer length of stay, higher ANC and lower platelet nadir counts during active ACS, increased involvement of 3 or more lung lobes, and presence of pleural effusions. A lower proportion of confirmed viral infections were found in the severe ACS cohort compared to mild ACS patients, although did not reach statistical significance. Future prospective studies investigating the utility of these specific laboratory and radiographic parameters as components of an ACS severity prediction score are warranted. Disclosures Tubman: Forma Pharmaceuticals: Consultancy; Novartis Pharmaceuticals: Honoraria, Research Funding; Global Blood Therapeutics: Consultancy, Research Funding; Perkin Elmer: Honoraria. Fasipe: Emmaus: Consultancy; Bluebird Bio: Consultancy; Global Blood Therapeutics: Consultancy, Other: Grant Review Committee ; Novartis: Consultancy; Pfizer: Research Funding.
Objectives: Sickle cell disease (SCD) is well recognized as a hypercoagulable state, however venous thromboembolism (VTE) risk factors in children remain largely unknown. In this study, we aim to describe the clinical characteristics, outcomes and recurrence of hospital acquired VTE in patients younger than 21 years of age. Study Design/Methods: Data were extracted from electronic medical records over a 10-year period (2011-2021). Data regarding sickle cell genotype, demographics, reason for admission, location of thrombus, presence of central venous catheter (CVC), intensive care unit (ICU) admission, presence of thrombophilia risk factors, resolution of VTE, mortality, and bleeding outcomes on anticoagulation were collected. Recurrence of VTE at 1 and 5 years was assessed. Descriptive statistics were used as indicated. Results: We identified a total of 21 VTE events over the ten-year study period. Six of these events occurred in those younger than 12 years of age. Fifteen (71%) VTE events occurred in the HbSS or HbSβThal genotypes compared to 8 (29%) in HbSC. Eleven (52%) patients were admitted with acute chest syndrome (ACS). Most VTE events were associated with ICU admissions (n=13, 62%) and presence of central venous catheter (n=12, 57%). Major bleeding on anticoagulation occurred in 10%.All patients had resolution of index VTE at 12 weeks. Recurrence rate for VTE at 5 years was 13%. One patient died from the VTE event. Conclusions: Our study highlights that VTE can complicate SCD in children and young adults. Hospital acquired VTE were most associated with ICU admission, CVC, and ACS, but larger studies are indicated to validate our findings.
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