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

People with diabetes have an increased risk of experiencing adverse COVID-19 outcomes. COVID-19 vaccination is, therefore, highly recommended. However, people with diabetes have an inherently elevated risk of thrombotic events and the impact of the vaccination on the coagulation system in this patient population remains to be elucidated. The aim of this study was to investigate the impact of COVID-19 vaccination on the haemostatic system in people with type 1 or type 2 diabetes. We evaluated the effects of COVID-19 vaccination (BioNTech Pfizer, Moderna, AstraZeneca) on standard coagulation parameters, whole blood coagulation (Thrombelastometry), platelet function (impedance aggregation), and thrombin generation (calibrated automated thrombography) in people with type 1 diabetes mellitus (n = 41) and type 2 diabetes mellitus (n = 37). Blood sampling points were prior to vaccination and two weeks after the respective vaccination. Thrombelastometry measurements indicated moderately increased clot formation post-vaccination in people with type 1, as well as with type 2, diabetes: “Clot formation times” were significantly shorter, and both “maximum clot firmness” and “alpha angles” were significantly higher, as compared to the respective pre-vaccination values. Therefore, TEM parameters were not altered after vaccination in patients receiving ASA. Moreover, platelet aggregation was enhanced in people with type 1 diabetes, and plasma levels of D-Dimer were increased in people with type 2 diabetes, following COVID-19 vaccination. All other standard coagulation parameters, as well as thrombin generation, were not affected by the vaccination. The coagulation responses of people with diabetes to COVID-19 vaccination were only subclinical and comparable to those observed in healthy individuals. Our findings suggest that people with diabetes do not face an increased activation of the coagulation post-vaccination.

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“…This is of particular interest, as people with diabetes are already at increased risk of thromboembolic events. [ 7 , 19 , 20 ]…”

Section: Discussionmentioning

confidence: 99%

Only Subclinical Alterations in the Haemostatic System of People with Diabetes after COVID-19 Vaccination

Paar

Aziz

Sourij

et al. 2022

Viruses

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“…Although TF is expressed in various cells, tissue inflammation enhances its expression in tissue macrophages [ 6 ]. On the other hand, diabetic and inflammatory states have been shown to increase blood TF levels despite almost undetectable blood TF levels in the physiological state [ 6 , 18 – 20 ]. The present study showed that the diabetic state increased plasma TF levels in mice, but did not affect TF expression in bone tissues, and also that femoral bone injury did not affect the expression of TF in injured sites.…”

Section: Discussionmentioning

confidence: 99%

“…We previously revealed the involvement of PAI-1 in delayed bone repair induced by a diabetic state in mice [ 15 – 17 ]. TF antigen levels and the number of TF-positive microvesicles were found to be elevated in the blood of diabetic patients [ 18 , 19 ]. However, it is important to note that several methods may be used to measure plasma TF levels, including antigen- and activity-based assays [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

Role of tissue factor in delayed bone repair induced by diabetic state in mice

et al. 2021

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Background Tissue factor (TF) is the primary activator of the extrinsic coagulation protease cascade. Although TF plays roles in various pathological states, such as thrombosis, inflammatory diseases, cancer, and atherosclerosis, its involvement in bone metabolism remains unknown. Materials and methods The present study examined the roles of TF in delayed bone repair induced by a diabetic state in mice using wild-type (WT) and low TF-expressing (LTF) male mice. A diabetic state was induced by intraperitoneal injections of streptozotocin (STZ). Results A prolonged diabetic state significantly reduced total and trabecular bone mineral densities (BMD) as well as cortical bone thickness in WT and LTF mice; these BMD parameters were similar between WT and LTF mice treated with or without STZ. The diabetic state induced in WT mice delayed the repair of the femur following injury. The diabetic state induced in LTF mice was associated with further delays in bone repair. In in vitro experiments, TF significantly decreased receptor activator of nuclear factor-κB ligand-induced osteoclast formation and osteoclastogenic gene expression in RAW264.7 cells. However, it did not affect the gene expression levels of runt-related transcription factor 2 and osterix as well as alkaline phosphatase activity in mouse primary osteoblasts. Conclusion Low TF state was associated with enhanced bone repair delay induced by diabetic state in mice. The TF-induced suppression of bone remodeling may be a contributing factor to the protective effects of TF against delayed bone repair in a diabetic state.

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

et al. 2020

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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

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

Cited by 6 publications

References 35 publications

Only Subclinical Alterations in the Haemostatic System of People with Diabetes after COVID-19 Vaccination

Only Subclinical Alterations in the Haemostatic System of People with Diabetes after COVID-19 Vaccination

Role of tissue factor in delayed bone repair induced by diabetic state in mice

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

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