A quality improvement initiative standardizing premedication for blood product transfusions.

For children with cancer, blood product transfusions are crucial, but can be complicated by transfusion reactions. To prevent these complications, premedication is often given, although not always evidence-based. Herein, we describe a significant decrease in the use of premedication (72%-28%) at our institution after the implementation of standardized guidelines, without an increase in transfusion reactions (3.2% prior vs. 1.5% after standardization). Importantly, there were no severe transfusion reactions leading to hospitalization or death. Our results provide evidence in favor of more judicious use of premedication prior to transfusions in patients 21 years and younger being treated for cancer.

Effects of COVID-19 vaccination on platelet counts and bleeding in children, adolescents, and young adults with immune thrombocytopenia.

Coronavirus disease 2019 (COVID-19) vaccines rarely cause de novo immune thrombocytopenia (ITP) but may worsen preexisting ITP in adults. Whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines impact platelet counts and bleeding in children, adolescents, and young adults (C-AYA) with preexisting ITP is unknown. We report here the very limited effect of COVID-19 vaccination on platelet counts and bleeding in a single-center series of 2 C-AYA with ITP. No patient experienced worsening bleeding and only one child had a significant decrease in platelet count which improved spontaneously to her baseline without intervention. SARS-CoV2 vaccination was safe in C-AYA with ITP in this small cohort.

Pediatric refractory immune thrombocytopenia: A systematic review.

Pediatric immune thrombocytopenia (ITP) is an acquired disorder associated with autoimmune destruction and impairment of platelet production in children. Some children exhibit poor or transient response to ITP-directed treatments and are referred to as having refractory ITP (rITP). There is currently no consensus on the definition of rITP, nor evidence-based treatment guidelines for patients with rITP. After a survey of pediatric ITP experts demonstrated lack of consensus on pediatric rITP, we pursued a systematic review to examine the reported clinical phenotypes and treatment outcomes in pediatric rITP. The search identified 253 relevant manuscripts; following review, 11 studies proposed a definition for pediatric rITP with no consensus amongst them. Most definitions included suboptimal response to medical management, while some outlined specific platelet thresholds to define this suboptimal response. Common attributes identified in this study should be used to propose a comprehensive definition, which will facilitate outcome comparisons of future rITP studies.

Therapeutic plasma exchange practices in immune thrombocytopenia related hospitalizations: Results from a nationally representative sample.

Per the American Society for Apheresis, therapeutic plasma exchange (TPE) is a Category III indication in the management of immune thrombocytopenia (ITP). This nationally representative study evaluates TPE utilization in hospitalized adults with a primary admission diagnosis of ITP. Hospitalizations with ITP as the primary admitting diagnosis were analyzed from the 2010 to 2014 National Inpatient Sample, the largest all-payer inpatient database in the United States. Univariate and multivariable logistic regressions were used to determine clinical outcomes in ITP patients undergoing TPE. Sampling weights were applied to generate nationally representative estimates. From 2010 to 2014, there were a total of 56,149 admissions with a primary admitting diagnosis of ITP, of which 0.66% admissions (n = 372) also coded TPE. Most subjects undergoing TPE were the highest disease severity class: major (34.6%) and extreme severity (31.0%), by all-patients refined diagnoses-related groups severity of illness subclass. After multivariable analysis, underlying severity of illness remained the most significant predictor of TPE (P < .001). ITP admissions with TPE had a high rate of comorbidities (50%) and significantly longer mean length of hospital stay than those without (P < .001). TPE was reported in ~0.6% of hospitalizations with ITP as the primary diagnosis in this nationally representative sample from 2010 to 2014. TPE was performed in patients with the highest severity of underlying illness, and higher rates of comorbidities.

Successful treatment and integrated genomic analysis of an infant with FIP1L1-RARA fusion-associated myeloid neoplasm.

FIP1L1-RARA-a ssociated neoplasm is a very rare and aggressive disease, with only 3 previously reported cases in the literature. Here, we describe a 9-month-old boy who presented with a FIP1L1-RARA fusion-associated myelodysplastic/myeloproliferative neoplasm-like overlap syndrome, with similarities and distinct features to both acute promyelocytic leukemia and juvenile myelomonocytic leukemia. Using a combined approach of chemotherapy, differentiating agents, and allogeneic hematopoietic stem cell transplant (allo-HCT), this patient remains in remission 20 months after allo-HCT. To our knowledge, this is only the second published pediatric case involving this condition and the only case with a favorable long-term outcome. Given the aggressive disease described in the previously published case report, as well as the successful treatment course described, the combinatorial use of chemotherapy, differentiation therapy, and allo-HCT for treatment of FIP1L1-RARA fusion-associated myeloid neoplasms should be considered.

Parsonage-turner syndrome associated with SARS-CoV2 (COVID-19) infection.

Parsonage-Turner Syndrome (PTS), also known as idiopathic brachial plexopathy or neuralgic amyotrophy, is an uncommon condition characterized by acute onset of shoulder pain, most commonly unilateral, which may progress to neurologic deficits such as weakness and paresthesias (Feinberg and Radecki, 2010 [1]). Although the etiology and pathophysiology of PTS remains unclear, the syndrome has been reported in the postoperative, postinfectious, and post-vaccination settings, with recent viral illness reported as the most common associated risk factor (Beghi et al., 1985 [2]). Various viral, bacterial, and fungal infections have been reported to precede PTS, however, currently there are no reported cases of PTS in the setting of recent infection with SARS-CoV2 (COVID-19). We present a case of a 17 year old female patient with no significant past medical or surgical history who presented with several weeks of severe joint pain in the setting of a recent viral illness (SARS-CoV2, COVID-19). MRI of the left shoulder showed uniform increased T2 signal of the supraspinatus, infraspinatus, teres minor, teres major, and trapezius muscles, consistent with PTS. Bone marrow biopsy results excluded malignancy and hypereosinophilic syndrome as other possible etiologies. Additional rheumatologic work-up was also negative, suggesting the etiology of PTS in this patient to be related to recent infection with SARS-CoV2 (COVID-19). Radiologists should be aware of this possible etiology of shoulder pain as the number of cases of SARS-CoV2 (COVID-19) continues to rise worldwide.

Use of plasma-derived factor X concentrate in neonates and infants with congenital factor X deficiency.

BACKGROUND: Congenital factor X deficiency (FXD) is a rare bleeding disorder that often presents with severe bleeding in the neonatal period. Long-term prophylaxis with infusions of FX-containing products is recommended in patients with FXD and a personal or family history of severe bleeding. A plasma-derived FX concentrate (pdFX) is approved for on-demand and prophylactic therapy in adults and children with FXD. The safety and efficacy of pdFX has been demonstrated in patients <12 years of age, yet limited data exist regarding its use in infants. PATIENTS/METHODS: This retrospective case series details clinical experience using pdFX in four neonates with moderate and severe FXD across four institutions. RESULTS AND CONCLUSIONS: All four patients presented in the first week of life with severe bleeding. Following treatment of the acute bleed, prophylactic pdFX was initiated at an average of 29 days of life and a dose of 69 IU/kg every 48 hours. Incremental recovery (IR) in three infants averaged 1.42 IU/dL per IU/kg (min-max: 1.06-1.67 IU/dL per IU/kg). One patient experienced thrombotic complications in the setting of sepsis. After a median follow-up of 26.5 months, no patient has experienced breakthrough bleeding episodes. Our study supports the use of pdFX in neonates and infants and suggests that higher pdFX dosing of 70 to 80 IU/kg every 48 hours based on the smallest available vial size is feasible. Because of variability in IR, close monitoring of FX activity should be used to guide dosing in this age group.

Platelet transfusion practices in immune thrombocytopenia related hospitalizations.

BACKGROUND: The role of platelet transfusions in management of Immune Thrombocytopenia (ITP) remains controversial. Current guidelines recommend that platelet transfusions in ITP be reserved for catastrophic hemorrhage or invasive surgical procedures. This study assesses the nationwide platelet transfusion practices in hospitalized children and adults with ITP. STUDY DESIGN AND METHODS: We studied hospitalizations with ITP as the primary admitting diagnosis from 2010-2014 in National Inpatient Sample (NIS), the largest all-payer inpatient database. Univariate and multivariable logistic regression analyses were used to determine factors predicting platelet transfusions. Sampling weights were applied to generate nationally representative estimates. Propensity score matching was used to perform sensitivity analyses. RESULTS: From 2010 to 2014, there were 78,376 admissions with ITP as the primary admission diagnosis (mean ± SD age: 45 ± 27 years; females 56%, children [age < 18 years] 22%) and 282,285 with ITP as one of all the admission diagnoses. Overall, 27% admissions with ITP as primary (children 4%) and 15% admissions with ITP as one of all the diagnoses documented at least one platelet transfusion. On multivariable adjustment the following factors were associated with worsening disease severity and a higher odds of platelet transfusion, adult age (adjOR = 9.03, 95% CI = 7.40-11.02), male gender (adjOR = 1.21, 95% CI = 1.11-1.31), bleeding occurrence (intracranial/gastrointestinal/genitourinary/epistaxis) (adjOR = 1.78, 95% CI = 1.61-1.96), admission to rural non-teaching hospital (adjOR = 1.85, 95% CI = 1.52-2.22), and small bed-size hospital (adjOR = 1.23, 95% CI = 1.05-1.45). Of admissions reporting platelet transfusions, only 26% reported a bleeding complication, and 11% had a major operating-room surgery/procedure. Overall, 65% of transfused patients had neither bleeding nor a major operative procedure during the hospitalization. Admissions with platelet transfusions had a significantly longer mean length of hospitalization 2.2 days (95% CI = 1.96-2.41, p < 0.001), and accrued higher mean total hospital charges; $31,150 USD (95% CI = 27,644-34,656, p < 0.001). However, platelet transfusions were not associated with in-hospital mortality (adjOR = 1.02, 95% CI = 0.73-1.45, p = 0.892). CONCLUSION: Platelets are administered to a small fraction of the hospitalized ITP patients. In a majority of these cases however, platelet usage does not appear to be concordant with the current guidelines or associated with improvement in clinical outcomes.

Managing incidentally diagnosed isolated factor VII deficiency perioperatively: a brief expert consensus report.

While isolated factor VII (FVII) deficiency is being more frequently diagnosed owing to improved preoperative screening procedures, there is no specific guideline for perioperative management of such patients. To complicate the issue, FVII activity levels seem to correlate less well with the risk of hemorrhage than the patient's past and family bleeding history do. We have devised expert consensus recommendations for managing such patients perioperatively, taking into consideration the personal and family bleeding history, the FVII activity level and the inherent bleeding risk of the procedure itself. We hope that clinicians will find this a useful tool in the decision-making process, thereby limiting the use of recombinant factor VIIa to those who need it most, and preventing possible thrombotic complications in those without a strong indication for its use.

Acute upper GI bleed in a 4-year-old boy: a case of atypical Burkitts lymphoma in a 4-year-old.

Lymphomas have been seen in the pediatric population; more frequently in patients with H. Pylori, Celiac disease, and/or patients with congenital or acquired immune deficiencies. We report a case of a 4-year old male with an acute gastric-intestinal bleed accompanied by a rare lymphoma.

Diagnostic challenges in a child with familial hemophagocytic lymphohistiocytosis type 3 (FHLH3) presenting with fulminant neurological disease.

BACKGROUND: Familial hemophagocytic lymphohistiocytosis (FHLH) is an autosomal recessively inherited multisystem disease characterized by fever, rash, splenomegaly, cytopenias, and variable central nervous system (CNS) manifestations. CASE HISTORY: We report the case of a 3-year-old boy who presented with splenomegaly and normocytic anemia 4 months after returning to the US from a region endemic for Leishmania infection. The child later developed progressive neurological impairment and had radiologic evidence of widespread demyelinating disease. Gene studies showed homozygosity for a mutation at Munc13-4, confirming FHLH type 3. DISCUSSION: The diagnostic uncertainty that accompanies FHLH was compounded by our patient's travel history and CNS disease mimicking acute disseminated encephalomyelitis (ADEM). Diagnostic criteria for hemophagocytic lymphohistiocytosis were not consistently met, despite aggressive disease. CONCLUSIONS: FHLH may present with fulminant demyelinating disease, mimicking ADEM, and without necessarily meeting previously defined clinical and laboratory criteria. We strongly recommend expeditious molecular testing and genetic counseling for FHLH mutations in cases of undiagnosed inflammatory CNS disease in the pediatric population.

Hepatic involvement in congenital acute megakaryoblastic leukemia: a case report with emphasis on the liver pathology findings.

We report the case of a 4-week-old infant diagnosed with acute megakaryoblastic leukemia with the t (1;22) (p13, q13) who presented with ascites caused by massive infiltration of hepatic sinusoids by leukemic cells. The bone marrow by microscopy and flow cytometry and the peripheral blood smear did not initially show the presence of blasts. Marrow fibrosis appeared after infiltrative disease in the liver and liver fibrosis. We describe the microscopic liver findings and associated clinical presentation that, in the absence of bone marrow involvement, can be difficult to diagnose as leukemia. Few cases have been reported in the medical literature with the liver as the primary site of involvement in congenital leukemia. Awareness of this unusual clinical presentation and of the characteristic liver pathology may facilitate the pathologic diagnosis.

Thalidomide is anti-angiogenic in a xenograft model of neuroblastoma.

Thalidomide has previously been shown to have anti-angiogenic properties. More recently, clinical efficacy of this agent has been demonstrated in multiple myeloma and prostate cancer. Neuroblastoma is the most frequent solid tumor of the abdomen of childhood, yet children with this disease frequently have metastases at presentation. Such patients have a very poor prognosis with current therapies. Thus, new approaches are needed. We have previously shown that VEGF antagonists can inhibit neoangiogenesis and tumor growth in experimental neuroblastoma. In this study, we investigated the anti-angiogenic and anti-tumor properties of thalidomide in a xenograft model of human neuroblastoma. Tumors were induced in athymic mice using the human neuroblastoma cell line NGP. Intraperitoneal thalidomide (100 mg/kg/dose) or vehicle was administered beginning one week after implantation, and animals euthanized at six weeks. Thalidomide treatment did not significantly alter tumor growth as compared with controls. However, thalidomide suppressed angiogenesis, as demonstrated both by fluorescein angiography and immunohistochemical staining, and induced apoptosis of endothelial cells in neuroblastoma xenografts. Quantification of microvessel density demonstrated a significant reduction of vasculature in treated tumors (p<0.004). Thalidomide induced co-option of host vasculature, an effect noted previously after VEGF blockade. This study demonstrates that thalidomide has anti-angiogenic properties in experimental neuroblastoma.

Cobalamin C disease presenting as hemolytic-uremic syndrome in the neonatal period.

Anew case of cobalamin C disease associated with hemolytic-uremic syndrome (HUS) in the neonatal period is described. A 28-day-old boy presented with failure to thrive, hypotonia, pancytopenia, and features of HUS (microangiopathic hemolytic anemia, thrombocytopenia, and renal failure). The possibility of the diagnosis of an underlying vitamin B12 disorder was prompted by evidence of megaloblastic changes on the peripheral smear and by finding in the literature a suggested association of neonatal HUS with this cobalamin-related metabolic disorder. Amino acid analysis showed elevated homocysteine levels in the plasma and increased levels of both homocysteine and methyl malonic acid in the urine. Diagnosis of cobalamin C disease was confirmed by complementation studies using skin fibroblasts. Therapy included parenteral hydroxocobalamin, carnitine, and leucovorin calcium (folinic acid). Cobalamin C disease should be considered in the diagnosis of patients presenting with HUS in infancy who have unexplained megaloblastosis, pancytopenia, neurologic impairment, and failure to thrive. Early diagnosis and institution of therapy may be effective in improving survival and quality of life.