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Increased tissue factor activity promotes thrombin generation at type 1 diabetes onset in children
Author(s) -
JasserNitsche Hildegard,
Haidl Harald,
Cvirn Gerhard,
Pohl Sina,
Gallistl Siegfried,
FröhlichReiterer Elke,
Schlagenhauf Axel
Publication year - 2020
Publication title -
pediatric diabetes
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.678
H-Index - 75
eISSN - 1399-5448
pISSN - 1399-543X
DOI - 10.1111/pedi.13086
Subject(s) - tissue factor , medicine , tissue factor pathway inhibitor , endocrinology , thrombin generation , thrombin , type 1 diabetes , coagulation , thrombomodulin , thromboplastin , protein c , diabetes mellitus , platelet
Abstract Objective In type 1 diabetes (T1D), a prothrombotic status due to elevated coagulation factors coincides with metabolic derailment. In a previous study, we discovered altered thrombin generation profiles in children with T1D. These alterations are potentially most pronounced at T1D onset and ameliorated after insulin treatment. We tested this hypothesis in a longitudinal study, measuring thrombin generation together with coagulation parameters in children at T1D onset and during follow‐up. Materials and methods Twenty‐three children (12 female, age: 9.4 [2.7‐17.3] years; median [range]) were tested at T1D onset and after long‐term insulin treatment. Thrombin generation was measured using calibrated automated thrombography. Tissue factor (TF) activity and tissue factor pathway inhibitor (TFPI) activity were measured using enzyme‐linked immunosorbent assay (ELISA). Results A procoagulant shift was observed in thrombin generation traces at T1D onset compared to follow‐up (time to peak: 5.67 [4.11‐7.67] min vs 6.39 [4.89‐10.44] min, P < .001). These alterations at T1D onset coincided with increased TF activity (5.18 [0.01‐12.97] pmol/L vs 2.67 [0.04‐10.41] pmol/L, P < .05) and increased TFPI activity (0.051 [0.038‐0.074] U/mL vs 0.035 [0.026‐0.056] U/mL, P < .05). Conclusion The procoagulant shift in thrombin generation at T1D onset is a result of increased TF activity, but this effect is partially counterbalanced by increased TFPI levels. Elevated TF and TFPI levels hint to a fragile hemostatic balance at the endothelial lining of blood vessels. Additional prothrombotic stimuli may tip over this balance explaining the increased thrombotic risk of children with T1D.