Dataset Information

Dynamic prediction of bleeding risk in thrombocytopenic preterm neonates.

ABSTRACT: Over 75% of severely thrombocytopenic neonates receive platelet transfusions, though little evidence supports this practice, and only 10% develop major bleeding. In a recent randomized trial, giving platelet transfusions at a threshold platelet count of 50x109/L compared to a threshold of 25x109/L was associated with an increased risk of major bleeding or mortality. This finding highlights the need for improved and individualized guidelines on neonatal platelet transfusion, which require accurate prediction of bleeding risk. Therefore, the objective of this study was to develop a dynamic prediction model for major bleeding in thrombocytopenic preterm neonates. This model allows for calculation of bleeding risk at any time-point during the first week after the onset of severe thrombocytopenia. In this multicenter cohort study, we included neonates with a gestational age <34 weeks, admitted to a neonatal intensive care unit, who developed severe thrombocytopenia (platelet count <50x109/L). The study endpoint was major bleeding. We obtained predictions of bleeding risk using a proportional baselines landmark supermodel. Of 640 included neonates, 71 (11%) had a major bleed. We included the variables gestational age, postnatal age, intrauterine growth retardation, necrotizing enterocolitis, sepsis, platelet count and mechanical ventilation in the model. The median cross-validated c-index was 0.74 (interquartile range, 0.69-0.82). This is a promising dynamic prediction model for bleeding in this population that should be explored further in clinical studies as a potential instrument for supporting clinical decisions. The study was registered at www.clinicaltrials.gov (NCT03110887).

SUBMITTER: Fustolo-Gunnink SF

PROVIDER: S-EPMC6821634 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Dynamic prediction of bleeding risk in thrombocytopenic preterm neonates.

Fustolo-Gunnink Susanna F SF Fijnvandraat Karin K Putter Hein H Ree Isabelle M IM Caram-Deelder Camila C Andriessen Peter P d'Haens Esther J EJ Hulzebos Christian V CV Onland Wes W Kroon André A AA Vijlbrief Daniël C DC Lopriore Enrico E van der Bom Johanna G JG

Haematologica 20190228 11

Over 75% of severely thrombocytopenic neonates receive platelet transfusions, though little evidence supports this practice, and only 10% develop major bleeding. In a recent randomized trial, giving platelet transfusions at a threshold platelet count of 50x10<sup>9</sup>/L compared to a threshold of 25x10<sup>9</sup>/L was associated with an increased risk of major bleeding or mortality. This finding highlights the need for improved and individualized guidelines on neonatal platelet transfusion, ...[more]

PMID: 30819913

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Project description:Critically ill patients often undergo central venous catheter placement during thrombocytopenia and/or coagulopathy. It is unclear whether severe coagulopathy increases the risk of postprocedural bleeding in critically ill patients with severe thrombocytopenia.DesignSingle-center retrospective cohort study.SettingAcademic mixed ICU in Amsterdam, the Netherlands.PatientsConsecutive severely thrombocytopenic (platelet count ≤ 50 × 109/L) patients who underwent central venous catheter placement between February 2016 and February 2020.InterventionsCentral venous catheter placement in patients with both severe thrombocytopenia and severe coagulopathy (international normalized ratio > 1.5 and/or activated partial thromboplastin time > 45 s) versus patients with severe thrombocytopenia and normal or mildly prolonged international normalized ratio and activated partial thromboplastin time.Measurements and main resultsWe included 289 central venous catheter placements in 175 patients, 112 in patients with and 172 in patients without severe coagulopathy. Median (interquartile range) platelet count was 27 (16-38) and equal for both groups. There were 44 bleeding episodes at the central venous catheter insertion site (15.5%), of which four (1.4%) were grade 2 and two (0.7%) were grade 3. There were 19 bleeding episodes (17.0%) versus 25 bleeding episodes (14.5%) in the coagulopathy and noncoagulopathy groups, of which one and five were of grade 2 or higher, respectively. After correction for confounders, coagulopathy had no effect on bleeding: odds ratio (95% CI) 0.96 (0.24-3.88). Before central venous catheter placement, 116 (40.8%) patients received platelet transfusion. Bleeding at the central venous catheter insertion site occurred in 19 of 116 patients (16.4%) and 25 of 168 patients (14.9%) who did and did not receive platelet transfusion. After correction for confounders, platelet transfusion had no effect on bleeding: odds ratio (95% CI) 0.73 (0.18-2.83).ConclusionsCoagulopathy was not associated with an increased bleeding risk in severely thrombocytopenic ICU patients undergoing ultrasound guided central venous catheter placement. Prophylactic platelet transfusion in patients with severe thrombocytopenia was not associated with a reduced risk of bleeding.

Project description:Congenital thrombotic thrombocytopenic purpura (TTP) is a rare hereditary disease with a high mortality rate; however, improved patient survival is possible with prompt diagnosis and treatment. The clinical features and mutation sites of a disintegrin and metalloproteinase with thrombospondin motifs 13 (ADAMTS13) in congenital TTP were analyzed in a neonate with suspected congenital TTP. High-throughput sequencing, polymerase chain reaction, and Sanger sequencing were utilized for screening of genes related to thrombocytopenic diseases and ADAMTS13 gene mutation testing on blood samples from the neonate and the parents. Domestic and foreign literature reporting the clinical features and variants of ADAMTS13 in neonates with congenital TTP were retrieved, compared, and analyzed. The patient in this case was a girl who had been born for 1 h and admitted to the hospital due to "dyspnea for 1 h." Routine blood tests on admission revealed profound thrombocytopenia. She quickly developed symptoms of systemic hemorrhage and eventually died. The neonate had two older sisters who had died of idiopathic thrombocytopenia and hemorrhage within 24 h of birth. Genetic testing showed that the neonate harbored a compound heterozygous mutation in ADAMTS13, c.1187G>A/c.1595G>T, which is a novel variant. Of the 12 cases (1 case in China and 11 cases in other countries) of congenital TTP in neonates that have been reported globally, ADAMTS13 mutation analysis was only performed in eight neonates. Common clinical manifestations included dyspnea of unknown etiology, bruising, jaundice, hemorrhage, and thrombocytopenia. Hence, the current case contributes to our understanding of the clinical manifestations and types of variants in neonates with congenital TTP. Our results demonstrate the efficacy of high-throughput sequencing technology in genetic testing of neonates suspected with congenital TTP and have revealed a novel compound missense mutation in ADAMTS13 that has not been reported in China or elsewhere.

Dataset Information

Dynamic prediction of bleeding risk in thrombocytopenic preterm neonates.

Publications

Dynamic prediction of bleeding risk in thrombocytopenic preterm neonates.

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