Assessment of Plasma Prothrombotic Factors in Patients with Buerger’s Disease.
Authors: Hus Iwona , Sokolowska Bozena , Chrapko Marek , Nowaczynska Aleksandra , Walter-Croneck Adam , Mazurek Kamila , Lewandowska Magdalena , Rolinski Jacek M. , Dmoszynska Anna 
Published: April 2020

Abstract
Buerger’s disease or thrombangiitis obliterans (TAO) is non artherosclerotic vascular disease that most commonly affects the small and medium-sized peripheral arteries and veins. Although a strong association with tobacco use has been established, the cause of the disease remains unknown. Possible pathogenic factors include autoimmune phenomena, haemostatic factors abnormalities and hyperhomocystynemia, however their role still remains controversial. In this study we investigated the role of blood coagulation and fibrinolytic factors abnormalities in the development of TAO. We assessed plasma activity of factor VII (FVII) factor VIII (FVIII), factor IX (FIX), plasminogen (PLG), urokinase type plasminogen activator (uPA) and its receptor (uPAR), uPA complex with plasminogen activator inhibitor 1 (uPA-PAI-1), anexin V, apolipoprotein A (ApoA), homocysteine, folic acid and serum lipids profile. Blood samples were collected from 37 patients with TAO (8 female and 29 male) with median age 39.5 years (ranging from 20 to 50 years). In patients with Buerger’s disease there were significantly higher levels of prothrombotic factors as compared to healthy control: anexin V (8.27±6.28 ng/ml vs 2.93±2.06 ng/ml, p=0.0003), FIX (109.72±30.05% vs 78.54±12.28%, p=0.000003), FVII (123.28±30.10% vs 104.36±43.38%, p=0.0001), FVIII (119.85±44.39% vs 60.19±20.77%, p=0.0000001), homocysteine (11.53±2.88 μmol/l vs 9.86±2.20 μmol/l, p=0.01) and fibrinogen (5.06±1.94mg/dL vs 3.31±1.03mg/dL, p=0.00007). Mean uPA, uPAR and uPA/PAI-1 complex plasma levels were also higher in patients with Buerger’s disease than in healthy control: 1067.07±264.97pg/mL vs 979.01±170.93pg/mL, p=0.0008; 1798.22±438.43pg/mL vs 1348.20±194.95pg/mL, p=0.000004; 303.60±288.16pg/mL vs 110.17±166.71pg/mL, p=0.000006, respectively. In contrast, plasma concentrations of ApoA and folic acid were significantly lower in patients with TAO compared to healthy control: 135.30±18.77pg/dL vs 156.46±19.97pg/dL, p=0.004 and 4.82±2.35mg/dL vs 6.84±2.70mg/dL, p=0.0006; res. Moreover there was a significant correlation between prothrombotic factors plasma levels: FIX and plasminogen (R=0.44) as well as between FVII and uPA-PAI complex (R=0.52). We found significant differences concerning studied parameters between smoking and non-smoking patients with TAO: i.e. significantly higher level of PLG (120.66±14.33pg/mL vs 108.07±17.97pg/mL, p=0.03), total cholesterol (198.36±43.95mg/dL vs 178.64±44.93mg/dL, p=0.001) and triglycerides (161.36±117.47mg/dL vs 103.50±63.20mg/dL, p=0.04), as well as lower plasma levels of folic acid (4.43±2.31mg/dL vs 5.59±2.39mg/dL, p=0.02) in smokers group. Coffee use correlated only with increased homocysteine plasma level (12.31±2.70 vs 9.96±2.68, p=0.04). In 72.2% of TAO patients, surgery was required due to aggressive disease. In this group, we found higher level of plasminogen (119.78±15.34pg/mL vs 105.12±16.35pg/mL, p= 0.04), FVII (128.50±28.90% vs 109.70±30.70%, p=0.03), total lipids (692.49±186,33mg/dL vs 514.00±96.30mg/dL, p=0,002), cholesterol 201.73±42.63mg/dL vs 162.00±38.46mg/dL, p=0.02) and triglycerides (163.62±110.70mg/dL vs 74.50±27.09mg/dL, p=0.001) as compared to the patients treated only conservatively. Our results indicate an important role of hemostatic risk factors in pathogenesis of Buerger’s disease with special regard to increased plasma concentration of homocysteine that was proved to cause lesions of blood vessels endothelium. Decreased serum level of folic acid that was found in TAO patients may contribute to hyperhomocysteinemia. Patients with aggressive clinical course of TAO, requiring surgical treatment had more disturbances in serum lipids. These findings suggest that diet supplementation of folic acid as well as normalization of lipids balance might influence clinical course of TAO.