The role of the fibrinolytic system laboratory markers in the assessment of the cerebral small vessel disease severity

Abstract

Background: Small vessel disease (SVD) is a common brain disease causing about 40% of all dementias and about 25% of ischemic strokes, which makes important the study of its pathophysiology and the search for its biomarkers. A number of studies have shown a significant role of endothelial dysfunction and nonspecific inflammation, as well as of some individual parameters of hemostasis disorders in the development of SVD.
 Aim: To identify the role of the laboratory markers of fibrinolytic system in the assessment of the severity of white matter lesions in patients with SVD.
 Materials and methods: This single center cross-sectional non-controlled observational study included 117 patients with dyscirculatory encephalopathy (chronic brain ischemia), with a mean ( SD) age of 57.7 11.5 years. Laboratory tests of the fibrinolytic system, endothelial dysfunction, markers of inflammation and for an integral assessment of plasma hemostasis were performed in all patients, including XIIa-dependent fibrinolysis, levels of plasminogen, alpha2-antiplasmin, plasminogen activator inhibitor 1 (PAI-1), fibrinogen, von Willebrand factor (vWF) and activity of blood coagulation factor VIII (FVIII), highly sensitive C-reactive protein and parameters of the thrombodynamics assay. In all the patients, brain magnetic resonance imaging was performed with the assessment of the white matter lesions by the Fazecas scale.
 Results: Depending on the identified neuroimaging SVD markers (assessed with the Fazecas scale), the patients were divided into the SVD group (n = 54) and no-SVD group (n = 63). Those with SVD were older than those without (65 9 vs 51 10 years; p 0.001), had higher prevalence of arterial hypertension (p 0.001), diabetes mellitus (p = 0.029) and past thrombotic events (p 0.001). The SVD patients, compared to those without SVD, had a higher time of XIIa-dependent fibrinolysis (7.6 2.9 vs 6.5 1.7 min, p = 0.032), higher alpha2-antiplasmin levels (111 [95117] vs 105 [95111]%, p = 0.016) and higher clot density (D) (22789 [2056726411] vs 20627 [1832422650] U, p 0.001), although the parameters were within the reference ranges. As far as the thrombodynamics is concerned, the SVD group had higher values for all test parameters, as well as higher levels of the inflammation and endothelial dysfunction markers. Increased time of XIIa-dependent fibrinolysis was associated with higher probability of periventricular and subcortical leukoareosis grade 2 by the Fazecas scale (odds ratio 1.31 [1.071.60], p = 0.009), including an increase in the size and number of gliosis areas. Higher plasminogen levels were associated with a lower probability of leukoareosis by the Fazecas scale (odds ratio 0.97 [0.950.98], p 0.001).
 Conclusion: The severity of fibrinolytic and hemostatic abnormalities correlates with the severity of brain SVD, thus forming the hypofibrinolytic and prothrombotic status of the patients with this disorder.