Background/Purpose:

D-dimers are degradation products of cross linked fibrin and are biomarkers of activation of the coagulation system. Plasma D-dimer levels can be raised in physiological and pathological non-thrombotic conditions and are thought to be related to a pro-thrombotic state.

Studies have shown raised D-dimer levels in systemic sclerosis (SSc), particularly in diffuse SSc (DcSSc). An association between raised D-dimer level and peripheral ischaemia in SSc has also been described, suggesting that this could be related to a pro-thrombotic state.

Methods:

Blood samples were drawn from 60 outpatients who met the 2013 ACR/EULAR classification criteria for SSc. Samples were analysed for Factor XIII (FXIII) activity (U/dL), D-dimer (ng/ml), and fibrinogen (g/L) levels, and activated partial thromboplastin time (aPTT) (s). Clinical data gathered included age, gender, disease subtype, autoantibody details, duration of SSc and complications of SSc. Associations of demographic and clinical characteristics with FXIII were assessed using linear regression, while associations with D-dimer were analysed using Fisher’s exact test and logistic regression.

Results:

Of the 60 patients assessed, 83.3% were female. Age range was 20-82 years, with a mean age of 60.4 years. In terms of SSc subtype, 51.7% had limited SSc (LcSSc). The duration of SSc ranged from 0.62 to 50.6 years, with a mean duration of 14 years. Antibody status was collected; 36.7% were anti-centromere antibody positive, 11.7% were anti-Scl 70 antibody positive, 16.7% were anti-RNA polymerase antibody positive, and 35% had other positive autoantibodies. An overlapping rheumatological condition was found in 15% of patients. Of all patients, 25% had diagnosis of pulmonary fibrosis (PF), 31.7% had a history of digital ulceration (DU), and 8.3% had active DU at the time of blood draw.

D-dimers were raised in 62.7% of the patients. Raised D-dimer was seen more frequently in lcSSc patients (77.4%) compared to dcSSc (46.4%, p=0.017). In addition, older age increased the odds of having raised D-dimer (OR 1.1, p=0.001). Higher fibrinogen was associated with increased odds for raised D-dimer (OR 6.5, p=0.001). There was no association between raised D-dimer level and PF, current or previous digital ulceration (DU).

Factor XIII activity was positively associated with age (for each year older, this increased by 0.75, p=0.007) but did not associate with diffuse subset, disease duration, autoantibody specificity, fibrinogen level or APTT. There was evidence for a weak association between raised D-dimer and FXIII, where patients with raised D-dimer had on average 13.4 U/dL higher FXIII levels compared to those with normal D-dimer, p=0.089.

Conclusion:

This study confirms that D-dimer levels are frequently elevated in SSc. In contrast to previous studies, our data suggest raised D-dimer level is more commonly associated with LcSSc.

There was no correlation between raised D-dimer level and duration of SSc. This is in contrast with other inflammatory markers such as CRP, which are raised in early SSc only. There was no association between D-dimer level and current or previous DU, suggesting that this feature of vascular dysfunction in SSc is not related to a thrombotic state.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/plasma-d-dimer-levels-are-more-frequently-elevated-in-limited-than-diffuse-cutaneous-systemic-sclerosis-but-do-not-reflect-disease-duration-or-vasculopathy/