Association of fibrin clot characteristics with development of ischemic stroke in patients with recently diagnosed type 2 diabetes

Q: What are the key findings of this study?

Baseline fibrin fiber density was lower in T2D patients who developed ischemic stroke than controls (4.2 vs 4.5 x10^22 Da/cm3, p=0.01), with an adjusted OR of 0.7 (95% CI 0.3-1.5) for top tertile.

Q: What is the clinical evidence from this study?

Study design: Case-Control. Population: Recently diagnosed type 2 diabetes (n=288). Intervention: Baseline fibrin fiber density (highest vs. lowest tertile) vs. Lowest tertile of fibrin fiber density (or matched diabetes controls without ischemic stroke). Primary outcome: Ischemic stroke (and baseline fibrin fiber density in x10^22 Da/cm^3) (OR 0.7, 95% CI 0.3-1.5, p=0.01).

Nicoline Daugaard; Else-Marie Bladbjerg; Helene Matilde Lundsgaard Svane; Thomsen RW; Jens Steen Nielsen; Moniek de Maat; Anna-Marie Bloch Münster

doi:10.1055/a-2802-3514

February 3, 2026TH OpenOpen Access

Association of fibrin clot characteristics with development of ischemic stroke in patients with recently diagnosed type 2 diabetes

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Key result

Lower baseline fibrin fiber density links to ischemic stroke in patients with type 2 diabetes.

OR 0.7
95% CI 0.3-1.5
P=0.01
n=288

Key Points

To examine whether in vitro fibrin clot properties predict ischemic stroke risk and correlate with plasma fibrinogen variants in recently diagnosed type 2 diabetes.
Conducted a nested case-control study matching 144 type 2 diabetes patients who developed ischemic stroke with 144 controls without stroke, followed over a median of 4.1 years.
Evaluated clot formation, lysis, and structural characteristics via turbidimetry alongside Spearman's rank correlations for absolute and relative levels of fibrinogen variants.
Baseline fibrin fiber density was significantly lower in future stroke cases than controls (4.2 [3.7–4.7] vs. 4.5 [4.0–4.9] × 10^22 Da/cm^3, p=0.01), but the highest versus lowest tertile yielded an adjusted OR of 0.7 (95% CI: 0.3–1.5).
Other clot features (Vmax, MA, OHP, and fiber diameter) showed imprecise trends toward increased stroke risk with adjusted ORs around 1.3 to 1.5 in the highest tertiles (e.g., MA OR: 1.5, 95% CI: 0.7–3.1).
Absolute concentrations of fibrinogen variants (fibrinogen αE, fibrinogen γ', and sialylated fibrinogen) consistently correlated with clot characteristics, whereas relative levels did not.

Study Design

Type

Case-Control (n=288)

Multicenter

Yes

PICO

P

Population

288 adults (median age ~66 years, 43.8% female) with recently diagnosed type 2 diabetes (<4 years), consisting of 144 incident ischemic stroke cases and 144 matched diabetes controls followed for a median of 4.1 years.

E

Exposure / Comparator

Baseline fibrin fiber density (highest vs. lowest tertile) vs Lowest tertile of fibrin fiber density (or matched diabetes controls without ischemic stroke)

O

Primary Outcome

Ischemic stroke (and baseline fibrin fiber density in x10^22 Da/cm^3) — OR 0.7 (0.3-1.5), p=0.01

Main Result

Odds Ratio: 0.7 (95% CI 0.3–1.5)

Absolute Event Rate: 4.2% vs 4.5%

p-value: p=0.01

Limitations

Plasma samples were mailed overnight at ambient temperature before freezing, which reduced maximum absorbance (MA) levels.
Plasma samples were only centrifuged once, risking PAI-1 release from platelet remnants.
Potential degradation of fibrinogen and clot properties during long-term storage at -80°C for up to 15 years.
Limited statistical power (sample size based on fibrinogen γ') and inability to perform subgroup analyses.
Limited plasma volume prevented confirmation of findings with additional methodologies.

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Implication

Nested case-control study examines fibrin clot traits in ischemic stroke risk among type 2 diabetes patients, suggesting complex relationships.

Abstract

Background Ischemic stroke occurs when a thrombus blocks a cerebral artery, and an important component is the fibrin clot. Different plasma fibrinogen variants have been associated with stroke risk in type 2 diabetes (T2D). We hypothesized that in vitro fibrin clot characteristics associate with stroke risk and correlate with fibrinogen variants. Objectives To investigate the association of fibrin clot characteristics with risk of ischemic stroke in T2D and the correlation of fibrinogen variants with clot characteristics. Methods In a nested case-control study with a median follow-up of 4.1 years, we included 144 T2D patients with ischemic stroke (cases) and 144 matched T2D patients without ischemic stroke (controls). Clot formation (velocity (Vmax), maximum absorbance (MA), overall hemostasis potential (OHP)), lysis, and structure (fiber density, diameter) were analyzed by turbidimetry. Clot characteristics were compared between cases and controls using a Mann Whitney test and associated with stroke risk using conditional logistic regression to determine associations with stroke risk. Spearman’s rank correlation was used to determine correlations between clot characteristics and fibrinogen variants (fibrinogen αE, fibrinogen γ´, and sialylated fibrinogen). Results Fibrin fiber density at baseline was significantly lower in future stroke cases (4.2 (3.7;4.7) x1022 Da/cm3) than in controls (4.5 (4.0;4.9) x1022 Da/cm3), p 0.01. Moreover, patients in the highest versus lowest tertile of fiber density had an adjusted OR for ischemic stroke of 0.7 (95% CI 0.3;1.5). Patients with higher Vmax, MA, OHP, and fiber diameter all had ischemic stroke ORs around 1.5, yet limited statistical precision of the estimates hampered firm conclusions. Absolute, but not relative, levels of fibrinogen variants correlated with clot characteristics. Conclusion In our study, turbidimetric fibrin clot characteristics were not convincingly associated with ischemic stroke in T2D. Absolute levels of fibrinogen variants correlated consistently with clot characteristics.

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Cite This Study

Daugaard et al. (2026) conducted a case-control in Recently diagnosed type 2 diabetes (n=288). Baseline fibrin fiber density (highest vs. lowest tertile) vs. Lowest tertile of fibrin fiber density (or matched diabetes controls without ischemic stroke) was evaluated on Ischemic stroke (and baseline fibrin fiber density in x10^22 Da/cm^3) (OR 0.7, 95% CI 0.3-1.5, p=0.01). Baseline fibrin fiber density was lower in T2D patients who developed ischemic stroke than controls (4.2 vs 4.5 x10^22 Da/cm3, p=0.01), with an adjusted OR of 0.7 (95% CI 0.3-1.5) for top tertile.

synapsesocial.com/papers/698435e5f1d9ada3c1fb536d https://doi.org/10.1055/a-2802-3514

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Association of fibrin clot characteristics with development of ischemic stroke in patients with recently diagnosed type 2 diabetes

Key Points

Study Design

PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Association of fibrin clot characteristics with development of ischemic stroke in patients with recently diagnosed type 2 diabetes

Key Points

Study Design

PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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