Bleeding in Critically Ill Children With Malignancy or Hematopoietic Cell Transplant: A Single-Center Prospective Cohort Study.

OBJECTIVES: To determine the incidence of bleeding in critically ill children with malignancy and to describe associated patient characteristics, interventions, and clinical outcomes. DESIGN: Prospective cohort study. SETTING: PICU in a specialized cancer hospital. PATIENTS: Children with malignancy or hematopoietic cell transplant 0-18 years of age were admitted to the PICU from November 2020 to November 2021. INTERVENTIONS: None. MEASUREMENTS: Patient demographic data, laboratory values, and PICU outcome data were collected. Bleeding was classified according to the Bleeding Assessment Scale in Critically Ill Children. MAIN RESULTS: Ninety-three bleeding patients were enrolled, and a total of 322 bleeding days were recorded. The median (interquartile range [IQR]) age was 5.8 (2.9-11.8) years and 56% (52/93) of the patients were male. There were 121 new bleeding episodes, in 593 at-risk person-days, translating into a 20% incidence rate per day (95% CI, 17-24%). The incidence of severe, moderate, and minimal bleeding was 2% (95% CI, 1-3), 4% (95% CI, 3-6), and 14% (95% CI, 12-17), respectively. Of the new bleeding episodes, 9% were severe, 25% were moderate and 66% were minimal. Thrombocytopenia was the only laboratory value independently associated with severe bleeding ( p = 0.009), as compared to minimal and moderate bleeding episodes. History of radiation therapy was independently associated with severe bleeding ( p = 0.04). We failed to identify an association between a history of stem cell transplant ( p = 0.49) or tumor type ( p = 0.76), and bleeding severity. Patients were transfused any blood product on 28% (95% CI, 22-34) of the bleeding days. Severe bleeding was associated with increased length of mechanical ventilation ( p = 0.003), longer PICU stays ( p = 0.03), and higher PICU mortality ( p = 0.004). CONCLUSIONS: In this prospective cohort of children with malignancy, the incidence rate of bleeding was 20%. Most events were classified as minimal bleeding. Low platelet count and radiation therapy were variables independently associated with severe bleeding episodes.

Bleeding Scales Applicable to Critically Ill Children: A Systematic Review.

OBJECTIVES: To summarize current bleeding scales and their validation to assess applicability to bleeding in critically ill children. DATA SOURCES: We conducted electronic searches of Ovid MEDLINE, Ovid EMBASE, Cochrane Library, and Web of Science Core Collection databases from database inception to 2017. STUDY SELECTION: Included studies contained a bleeding score, bleeding measurement tool, or clinical measurement of hemorrhage. DATA EXTRACTION: We identified 2,097 unique citations; 20 full-text articles were included in the final review. DATA SYNTHESIS: Of the 18 studies that included subjects (two others were expert consensus definitions), seven (39%) were pediatric-only, seven (39%) were adult-only, and four (22%) included both adults and children. Nine (50%) occurred with inpatients (two studies in critical care units), seven (39%) involved outpatients and two (11%) included both inpatients and outpatients. Thirty-nine percent of the scales were developed for those with idiopathic thrombocytopenic purpura and only two (12%) described critically ill patients. The majority (80%) included need for treatment (either RBC transfusion or surgical intervention). The majority (65%) did not report measures of reliability or validation to clinical outcomes. CONCLUSIONS: There is a lack of validated bleeding scales to adequately assess bleeding and outcomes in critically ill children. Validated scales of bleeding are necessary and urgently needed.

Epidemiology of Bleeding in Critically Ill Children With an Underlying Oncologic Diagnosis.

OBJECTIVES: Critically ill children with malignancy have significant risk of bleeding but the exact epidemiology is unknown. We sought to describe severe bleeding events and associated risk factors in critically ill pediatric patients with an underlying oncologic diagnosis using the newly developed Bleeding Assessment Scale in Critically Ill Children definition. DESIGN: Retrospective cohort study. SETTING: PICU in comprehensive cancer center. PATIENTS: Children ages 28 days to 18 years with an underlying oncologic diagnosis admitted to the PICU during 2018. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Two-hundred sixty-seven admissions met inclusion criteria. Sixty-four percent (171/267) were male, with a median (interquartile range) age of 6.3 years (3.1-12.1 yr). Nine percent (23/267) had at least one severe bleeding event during their PICU admission. There were no significant differences between those with severe bleeding and those without, with respect to gender (p = 0.07), age (p = 0.66), weight (p = 0.76), or transplant status (p = 0.18). There was a difference in the frequency of severe bleeding based on underlying oncologic diagnosis (p = 0.009). For patients with severe bleeding, the median (interquartile range) platelet count and international normalized ratio on the day of bleeding were 102 × 109/L (40-181 × 109/L) and 1.36 (1.26-1.51), respectively. Eighty-seven percent patients (20/23) with severe bleeding received at least one blood component in response to bleeding. Two patients received antifibrinolytics. Patients with severe bleeding had significantly fewer PICU-free days (p = 0.001), fewer ventilator-free days (p < 0.001), and higher 28-day mortality (p = 0.003). CONCLUSIONS: Severe bleeding occurred in nearly one-tenth of critically ill children with an underlying oncologic diagnosis without severe thrombocytopenia or coagulopathy. The vast majority received blood component therapy, but few received hemostatic medication. Studies are needed to guide the treatment of severe bleeding in this vulnerable patient population.

Orbital volume and shape in Treacher Collins syndrome.

Orbito-palpebral reconstruction is a challenge in Treacher Collins syndrome (TCS). This study investigates orbital phenotypes in TCS using cephalometry and orbital shape analysis. Eighteen TCS and 52 control patients were included in this study, using the Dr Warehouse database. Orbital cephalometry was based on 20 landmarks, 10 planes, 16 angles, and 22 distances. Orbits were segmented. Registration-based, age-specific mean models were generated using semi-automatic segmentation, and aligned and compared using color-coded distance maps - mean absolute distance (MAD), Hausdorff distance (HD), and Dice similarity coefficient (DSC). Symmetry was assessed by mirroring and DSC computing. Central orbital depth (COD) and medial orbital depth (MOD) allowed 100% of orbits to be classified. COD and lateral orbital depth (LOD) were different from the controls. Average MAD between TCS and controls was ≤1.5 mm, while for HD it was >1.5 mm, and for DSC <1. TCS orbits were more asymmetrical than controls, and orbital volumes were smaller when age was considered as a confounding factor, and had a trend for normalization with age. This report emphasizes the importance of combining different morphometric approaches in the phenotype characterization of non-trivial structures such as the orbit, and supports composite skeletal and soft-tissue strategies for the management of the peri-orbital region.