Hospital acquired venous thromboembolism in children with sickle cell disease.

Sickle cell disease (SCD) is well recognized as a hypercoagulablestate, however, it remains unclear whether a subgroup of children with SCD at higher risk of venous thromboembolic event (VTE) during hospitalization may benefit from thromboprophylaxis. Our objectives were to describe the clinical characteristics, outcomes and recurrence of hospital acquired VTE in patients with SCD younger than 21 years. This was a single center retrospective study. Data regarding demographics, reason for admission, location of VTE, risk factors like central venous catheter (CVC), intensive care unit (ICU) admission among others were extracted from electronic medical records over a 10-year study period (2011-2021). Recurrence of VTE at 1 and 5 years was assessed. Descriptive statistics were used as indicated. We identified a total of 20 VTE events over the 10-year study period. Six of these events occurred in those younger than 12 years of age. Fourteen (70%) VTE events occurred in the HbSS or HbSßThal0 genotypes compared to 6 (30%) in HbSC. Most common VTE was isolated pulmonary embolism (PE) (n = 10, 50%). VTE were most often associated with acute chest syndrome (ACS) (n = 14, 70%), ICU admissions (n = 10, 50%) and CVC (n = 5/9, 55%). One patient died from the VTE event. One patient with additional underlying risk factors had a recurrent VTE at 13 months. Our study suggests that ICU admission, ACS and presence of CVC increases the risk of VTE in children and young adults with SCD, but larger studies are indicated to validate our findings.

Improving Time to Antibiotic Administration for Pediatric Oncology Patients With New-Onset Fever.

PURPOSE: Time to antibiotic administration (TTA) in <60 minutes for children with neutropenic fever presenting to an emergency room is associated with reduced incidence of sepsis and intensive care admission. As such, TTA is used as a national quality metric for pediatric oncology patients. At our center, in 2020, 19% of the hospitalized patients with a new fever encounter were receiving antibiotics in <60 minutes, prompting a multidisciplinary approach to reach a goal of >90% in all pediatric patients with cancer with a new fever. METHODS: A multidisciplinary team completed four Plan-Do-Study-Act cycles between March 2021 and September 2023. We implemented education initiatives, an updated handoff smartphrase guiding the on-call team, an antibiotic champion (AC) nursing role, a revised fever plan for handoff, a rapid-response team to address new fevers, and an algorithm for blood culture collection. Data were collected, analyzed, and reported biweekly with feedback sought for delays in TTA. RESULTS: There was a total of 639 new fevers in 329 unique oncology patients. As of September 4, 2023, average TTA decreased from 89 minutes at baseline to 46.4 minutes for more than 12 months. The percentage of patients receiving first dose of antibiotic in <60 minutes also increased from 19% to 93.7%, which was sustained as well. The most effective interventions were creation of the AC role and streamlining the blood culture collection process. CONCLUSION: This project demonstrates the importance of multidisciplinary involvement for providing optimal care. Specific implementation of targeted education, an AC role, and development of an algorithm streamlining the processes led to meaningful targeted improvements. Further analyses will explore the impact of these interventions on patient outcomes.

Multi-center retrospective study of children with sickle cell disease admitted to pediatric intensive care units in the United States.

Data on outcomes and interventions for children with sickle cell disease (SCD) admitted to a pediatric intensive care units (PICU) are unknown. We provide the first comprehensive multi-center report on PICU interventions associated with death, the need for invasive respiratory support or stroke among critically ill children with SCD. We collected retrospective multi-center cohort data from January 1, 2012 to December 31, 2019 utilizing the Virtual Pediatric Systems, LLC database. We identified 3388 unique children with SCD, accounting for a total of 5264 PICU admissions from 138 PICUs. The overall mortality rate for the PICU admissions cohort was 1.8% (95/5264 PICU admissions, 95/3388 [2.8%] of all unique patients), the rate of needing of needing Invasive Respiratory Support (IRS, a composite category of exposure) was 21.3% (872/4093 PICU admissions with complete data) and the overall rate of stroke (ischemic or hemorrhagic) was 12.5% (657/5264 PICU admissions). In multivariable analysis adjusting for admission age category, sex, race/ethnicity, PRISM-3 score at admission, exposure to IRS, quartile of unit volume of patients with SCD, and patient origin, admitted children who needed invasive respiratory support (IRS) had higher adjusted odds ratios for mortality (adjusted odds ratio [aOR], 19.72; 95% confidence interval [CI] 8.98-43.29; p < 0.001), although admitted children > 2 years old had decreased aOR for needing IRS (aOR 0.25-0.62; 95% CI 0.16-0.94; p < 0.001-0.025). By contrast, admitted children > 2 years old had a strikingly increased aOR for stroke (aOR 7.57-16.32; 95% CI 2.25-52.15; p < 0.001). These groups may represent PICU-specific subsets of patients with SCD who are at higher risk for more serious illness and should deserve early consideration for referral to a pediatric institution providing comprehensive care for patients with SCD.

The NLRP3 inflammasome fires up heme-induced inflammation in hemolytic conditions.

Overactive inflammatory responses are central to the pathophysiology of many hemolytic conditions including sickle cell disease. Excessive hemolysis leads to elevated serum levels of heme due to saturation of heme scavenging mechanisms. Extracellular heme has been shown to activate the NLRP3 inflammasome, leading to activation of caspase-1 and release of pro-inflammatory cytokines IL-1ß and IL-18. Heme also activates the non-canonical inflammasome pathway, which may contribute to NLRP3 inflammasome formation and leads to pyroptosis, a type of inflammatory cell death. Some clinical studies indicate there is a benefit to blocking the NLRP3 inflammasome pathway in patients with sickle cell disease and other hemolytic conditions. However, a thorough understanding of the mechanisms of heme-induced inflammasome activation is needed to fully leverage this pathway for clinical benefit. This review will explore the mechanisms of heme-induced NLRP3 inflammasome activation and the role of this pathway in hemolytic conditions including sickle cell disease.