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Increased tissue factor activity promotes thrombin generation at type 1 diabetes onset in children

Hildegard Jasser-Nitsche1, Harald Haidl1, Gerhard Cvirn2

  • 1Department of Paediatrics and Adolescent Medicine, Division of General Paediatrics, Medical University of Graz, Graz, Austria.

Pediatric Diabetes
|July 22, 2020
PubMed

Insights

Children with type 1 diabetes (T1D) show altered thrombin generation at diagnosis, linked to increased tissue factor (TF) and tissue factor pathway inhibitor (TFPI) levels. Insulin treatment helps normalize these prothrombotic markers.

Area of Science:

  • Pediatric Endocrinology
  • Hemostasis and Thrombosis
  • Metabolic Disorders

Background:

  • Type 1 diabetes (T1D) is associated with a prothrombotic state due to elevated coagulation factors and metabolic changes.
  • Previous research indicated altered thrombin generation profiles in children with T1D.
  • These alterations may be most significant at T1D onset and improve with insulin therapy.

Purpose of the Study:

  • To investigate the longitudinal changes in thrombin generation and coagulation parameters in children with T1D.
  • To test the hypothesis that thrombin generation alterations are most pronounced at T1D onset and improve after insulin treatment.

Main Methods:

  • Longitudinal study of 23 children with T1D at diagnosis and during follow-up.
  • Thrombin generation measured using calibrated automated thrombography.
  • Tissue factor (TF) and tissue factor pathway inhibitor (TFPI) activity assessed via ELISA.

Main Results:

  • A procoagulant shift in thrombin generation was observed at T1D onset compared to follow-up (P < .001).
  • Increased TF activity (P < .05) and TFPI activity (P < .05) were noted at T1D onset.
  • Thrombin generation alterations at onset were linked to elevated TF activity, partially offset by increased TFPI.

Conclusions:

  • The procoagulant shift in thrombin generation at T1D onset is driven by increased TF activity, modulated by TFPI.
  • Elevated TF and TFPI levels suggest a precarious hemostatic balance in children with T1D.
  • These findings may explain the increased thrombotic risk in children with T1D, highlighting the need for further investigation.
Abstract

Keywords:
T1Dendothelial damagethrombin generation

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