Increased von Willebrand factor parameters in children with febrile seizures

Abstract

IntroductionPrimary blood coagulation and wound sealing are orchestrated by von Willebrand factor (VWF), a large multimeric glycoprotein. Upon release of arginine vasopressin (AVP), VWF containing high molecular weight multimers is secreted. By measuring copeptin, the C-terminal part of the AVP prohormone, we recently found strongly increased AVP levels in children with febrile seizures (FS) as compared to children with fever but without seizures. It is unknown if increased AVP levels in FS are of any biological function. Therefore, our a priori hypothesis was that children with FS have increased VWF parameters in parallel with higher AVP levels.MethodsWe conducted a prospective, cross-sectional study of children aged between 6 months and 5 years. Children that presented at our emergency department with fever or a recent FS (within four hours) were evaluated to be included to the study. We measured serum copeptin and VWF parameters, including analyses of VWF:Antigen (WVF:Ag), VWF:collagen binding activity (VWF:CB) and VWF multimers in children with FS, febrile infections without seizures and additionally, in a non-febrile control group.ResultsWe included 54 children in our study, 30 with FS, 10 in the febrile control group, and 14 in the non-febrile control group. Serum copeptin levels were significantly higher in children with FS (median [IQR] 24.73 pmol/l [13.65–68.65]) compared to the febrile control group (5.66 pmol/l [4.15–8.07], p = 0.002) and the non-febrile control group (4.78 pmol/l [3.33–5.3], p<0.001). VWF:CB levels were also significantly higher in children with FS (VWF:CB 2.29 U/ml [1.88–2.97]) as compared to the febrile (VWF:CB 1.41 U/ml [1.27–1.93], p = 0.048) and the non-febrile control group (VWF:CB 1.15 U/ml [0.98–1.21], p<0.001). VWF:Ag tended to be higher in children with FS compared to both control groups. Multivariate regression analysis revealed FS and copeptin as major determinants of VWF:CB.ConclusionsOur results suggest that increased secretion of AVP in children with FS is associated with higher plasma levels of VWF parameters. Especially VWF:CB may serve as additional biomarker in the diagnosis of FS.

Acute Phase Serum Leptin, Adiponectin, Interleukin-6, and Visfatin Are Altered in Chinese Children With Febrile Seizures: A Cross-Sectional Study

“…Febrile seizures (FS) are one of the most common clinical diseases in pediatric neurology. It occurs between 6 months and 6 years of age and occurs in ~2–5% of children in the United States and Western Europe, ~5–14% in Asian countries, and 3–5% in China ( 1 – 3 ). According to the age, frequency, duration, and type of seizures, FS is divided into simple febrile seizures (SFS) and complex febrile seizures (CFS).…”

“…Imuekemhe et al in 1989 and 1996 found that lactic acid in the serum and cerebrospinal fluid of children with FS was significantly increased ( 6 ). Wellmann et al found that the serum copeptin and Von Willebrand factor (VWF) of children with FS were significantly higher than those of the control group ( 3 , 7 ). The levels of proinflammatory cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), and anti-inflammatory cytokines, such as interleukin-4 (IL-4), in the peripheral blood of children with FS also exhibited significant changes, suggesting that these inflammatory molecules may play an important role in the pathogenesis of FS ( 8 – 10 ).…”

Serum Neurofilament Levels in Children With Febrile Seizures and in Controls

“…The routine use of prolactin is not recommended due to limited accuracy. Moreover, copeptin levels were significantly higher in the FS group than in the control group and may be more useful for distinction of the underlying cause of the convulsive event ( Stocklin et al, 2015 ; Pechmann et al, 2019 ). In contrast to these findings, our results could not provide additional support that copeptin and prolactin have the potential to predict upcoming convulsive events because none of the two biomarkers were related to recurrent seizures.…”

Distinguishing and Biochemical Phenotype Analysis of Epilepsy Patients Using a Novel Serum Profiling Platform

“…A PubMed/Medline search of these 100 differentially expressed peptides/proteins in Table 3 and Table 4 showed 70% were related to neurological function, 45% to immune/inflammation, 32% to seizures/epilepsy, 24% to ion-channels, and 10% to blood–brain barrier (BBB). Seizure/epilepsy related proteins (shaded cells in Table 3 and Table 4 ) include: SLIT2 (Slit guidance ligand 2 [ 29 ]), EPHB2 (EphrinB receptor 2, [ 30 ]), LAMA2 (Laminin alpha-2, [ 31 ]), ADAM11 (ADAM (A disintegrin and metalloprotease domain 11, [ 32 ]), P2RX7 (Purinergic receptor P2X 7, [ 33 ]), SLC4A4 (Solute carrier family 4 member 4, [ 34 ]), KCNQ2 (Potassium Voltage-Gated Channel Subfamily Q Member 2, [ 9 ]), VWF (von Willebrand factor, [ 35 ]), RYR2 (Ryanodine receptor 2, [ 36 ]), RECK (Reversion Inducing Cysteine Rich Protein With Kazal Motifs, [ 37 ]), ATP7B (ATPase Copper Transporting Beta, [ 38 ]), NF1 (Neurofibromin 1, [ 39 ]), HDC (Histidine Decarboxylase, [ 40 ]). Two other important seizure/epilepsy related proteins in Table 3 and Table 4 are CACNA2D2 (Calcium Voltage-Gated Channel Auxiliary Subunit Alpha2 delta 2, [ 41 ]) and ASTN2 (Astrotactin 2, [ 42 ]).…”