Genetic variants of the vitamin K dependent coagulation system and intraventricular hemorrhage in preterm infants

Schreiner, Christine; Suter, Sévérine; Watzka, Matthias; Hertfelder, Hans‐Jörg; Schreiner, Felix; Oldenburg, Johannes; Bartmann, Peter; Heep, Axel

doi:10.1186/1471-2431-14-219

Cited by 20 publications

(26 citation statements)

References 27 publications

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“…Several reports have revealed that genetic factors can influence the vitamin K-dependent coagulation system and intraventricular hemorrhage [14,15]. Further studies regarding the usefulness of testing for genetic variants to prevent and diagnose VKDB are warranted.…”

Section: Diagnosis Of Vkdb In Infancymentioning

confidence: 99%

“…A frequent single nucleotide polymorphism (SNP)-G-1639A-within the VKORC1 promoter has been identified as a major determinant of coumarin sensitivity, reducing the activity of vitamin K epoxide reductase enzyme to 50% of that of the wild GG type. Polymorphisms in VKORC1 (G-1639A) and coagulation factor 7 (F7-323 Ins10) were reportedly associated with intraventricular hemorrhage or low factor VII levels [14]. Recently, the presence of variant alleles in VKORC1 (SNP: rs9923231) was reportedly associated with vitamin K deficiency bleeding (VKDB) [15].…”

Section: Introductionmentioning

confidence: 99%

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Vitamin K Deficiency Bleeding in Infancy

Araki

Shirahata

2020

Nutrients

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Vitamin K is essential for the synthesis of few coagulation factors. Infants can easily develop vitamin K deficiency owing to poor placental transfer, low vitamin K content in breast milk, and poor intestinal absorption due to immature gut flora and malabsorption. Vitamin K deficiency bleeding (VKDB) in infancy is classified according to the time of presentation: early (within 24 h), classic (within 1 week after birth), and late (between 2 week and 6 months of age). VKDB in infancy, particularly late-onset VKDB, can be life-threatening. Therefore, all infants, including newborn infants, should receive vitamin K prophylaxis. Exclusive breastfeeding and cholestasis are closely associated with this deficiency and result in late-onset VKDB. Intramuscular prophylactic injections reduce the incidence of early-onset, classic, and late-onset VKDB. However, the prophylaxis strategy has recently been inclined toward oral administration because it is easier, safer, and cheaper to administer than intramuscular injection. Several epidemiological studies have shown that vitamin K oral administration is effective in the prevention of VKDB in infancy; however, the success of oral prophylaxis depends on the protocol regimen and parent compliance. Further national surveillance and studies are warranted to reveal the optimal prophylaxis regimen in term and preterm infants.

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Section: Diagnosis Of Vkdb In Infancymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Vitamin K Deficiency Bleeding in Infancy

Araki

Shirahata

2020

Nutrients

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“…24,31 One 24 of two studies found decreased FX activity in neonates with IVH. 24,31 A combined FII/VII/X activity assay was used in two studies, with no significant difference observed between the two groups of neonates. 38,40 Eight studies measured fibrinogen concentration, 10,11,23 25,35,37,39,40 among which seven reported no difference between the two groups.…”

Section: Secondary Hemostasismentioning

confidence: 99%

The Role of Platelets in Premature Neonates with Intraventricular Hemorrhage: A Systematic Review and Meta-Analysis

Grevsen

Hviid

Hansen

et al. 2019

Semin Thromb Hemost

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Intraventricular hemorrhage (IVH) affects up to 22% of extremely low birth weight neonates. Impaired coagulation might contribute to the pathogenesis of IVH. The aims of this study were to summarize the current knowledge on the role of platelet indices in premature neonates with IVH and to provide an overview of secondary hemostasis parameters as well as fibrinolysis in premature neonates with IVH. The review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The databases PubMed, Embase, Scopus, and Web of Science were searched on March 7, 2019, without time restrictions. In total, 30 studies were included. Most studies investigated the significance of platelet counts and/or mean platelet volume (MPV). The meta-analysis showed that at day 1 of life, neither platelet count nor MPV differed significantly between neonates with or without IVH (standardized mean difference [SMD]: –0.15 × 109/L, 95% confidence interval [CI]: –0.37 to 0.07 and SMD: 0.22 fl, 95% CI: –0.07 to 0.51, respectively). However, platelet counts < 100 × 109/L were associated with an increased risk of IVH. Secondary hemostasis parameters did not differ between neonates with and without IVH. Fibrinolysis was only sparsely investigated. In conclusion, platelet counts < 100 × 109/L were associated with an increased risk of IVH in premature neonates. The impact of secondary hemostasis was only sparsely investigated but seemed to be minor, and the role of fibrinolysis in IVH in premature neonates needs further research. Whether reduced platelet function is associated with an increased risk of IVH in premature neonates remains to be investigated.

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“…27 Finally, the role of vitamin K in IVH has been investigated across the past 20 years, and a recent unreplicated study of polymorphisms in genes encoding vitamin D epoxide reductase complex 1 (VKORC1 – 1639G>A) and coagulation factor 7 (F7-323Ins10) suggests that genetic variants in the vitamin K-dependent coagulation system influence IVH risk in preterm infants, although further studies are necessary. 50 …”

Section: Clinical Studies Suggest Coagulation Inflammation and Vascumentioning

confidence: 99%

Genes and environment in neonatal intraventricular hemorrhage

Ment

Ådén

Bauer

et al. 2015

Seminars in Perinatology

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Emerging data suggest intraventricular hemorrhage (IVH) of the preterm neonate is a complex disorder with contributions from both the environment and the genome. Environmental analyses suggest factors mediating both cerebral blood flow and angiogenesis contribute to IVH, while candidate gene studies report variants in angiogenesis, inflammation and vascular pathways. Gene-by-environment interactions demonstrate the interaction between the environment and the genome, and a non-replicated genome-wide association study suggests that both environmental and genetic factors contribute to the risk for severe IVH in very low birth weight preterm neonates.

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Genetic variants of the vitamin K dependent coagulation system and intraventricular hemorrhage in preterm infants

Cited by 20 publications

References 27 publications

Vitamin K Deficiency Bleeding in Infancy

Vitamin K Deficiency Bleeding in Infancy

The Role of Platelets in Premature Neonates with Intraventricular Hemorrhage: A Systematic Review and Meta-Analysis

Genes and environment in neonatal intraventricular hemorrhage

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