Plasma levels of hemostasis inhibitors and MRI outcomes in multiple sclerosis

Objective: To investigate the association between plasma levels of hemostasis inhibitors and MRI outcomes in multiple sclerosis (MS). Background: The role of hemostasis inhibitors in MS is not well understood. Several studies suggest the crosstalk between inflammation, immunity and coagulation in the MS pathogenesis. Improved knowledge of the role of hemostasis inhibitors could lead to better understanding of the anticoagulation/anti-inflammatory pathways in MS. Design/Methods: 3T MRI exams and plasma levels of hemostasis inhibitors levels were evaluated in 138 MS patients (mean age, 54 years; 72.5% female; median EDSS 3.5; average mean disease duration 21 years) and 42 age- and sex-matched healthy individuals (HI), collected in the Cardiovascular, Genetic and Environmental (CEG) study in MS. In particular, disintegrin-like and metalloprotease with thrombospondin type 1 motif 13 (ADAMTS13), heparin cofactor II (HCII), tissue factor pathway inhibitor (TFPI) and thrombomodulin (TM) plasma profiles were evaluated by magnetic Luminex assays and ELISA. Associations between hemostasis inhibitors and MRI outcomes were assessed. Results: Lower ADAMTS13 levels were found in MS patients compared to HI (1548±481 ng/mL vs 1733±562 ng/mL, p=0.038), and in MS with cerebral microbleeds compared to those without (1257±459 ng/mL vs 1566±479 ng/mL, p=0.028). In HI, decreased HCII levels were associated with larger cortical (p=0.003), brain parenchyma (p=0.005) and thalamus (p=0.013) volumes, and lower lateral ventricular volume (p=0.043) and T2 (p=0.045) lesion volumes (p=0.048). Conclusions: Normal levels of HCII, TM and TFPI, and decreased ADAMTS13 levels, particularly in patients with cerebral microbleeds are observed in MS patients. Data suggest a protective role of HCII on MRI outcomes in HI, not evident in MS patients. Further studies are needed to clarify the association of hemostasis inhibitors with the tissue injury in the CNS.