Factors Affecting the Thrombolytic-Treatment-Related Outcomes in Patients with Acute Lower Limb Ischaemia

Objective: Increasing data supports the role of bacterial inflammation in adverse events of cardiovascular and cerebrovascular diseases. In our previous research, DNA of bacterial species found in coronary artery thrombus aspirates and ruptured cerebral aneurysms were mostly of endodontic and periodontal origin, where Streptococcus mitis group DNA was the most common. We hypothesized that the genomes of S mitis group could be identified in thrombus aspirates of patients with lower limb arterial and deep venous thrombosis. Methods: Thrombus aspirates and control blood samples taken from 42 patients with acute or acute-on-chronic lower limb ischemia (Rutherford I-IIb) owing to arterial or graft thrombosis (n 1⁄4 31) or lower limb deep venous thrombosis (n 1⁄4 11) were examined using a quantitative real-time polymerase chain reaction to detect all possible bacterial DNA and DNA of S mitis group in particular. The samples were considered positive, if the amount of bacterial DNA in the thrombus aspirates was 2-fold or greater in comparison with control blood samples. Results: In the positive samples the mean difference for the total bacterial DNA was 12.1-fold (median, 7.1), whereas the differences for S mitis group DNA were a mean of 29.1 and a median of 5.2-fold. Of the arterial thrombus aspirates, 57.9% were positive for bacterial DNA, whereas bacterial genomes were found in 75% of bypass graft thrombosis with 77.8% of the prosthetic grafts being positive. Of the deep vein thrombus aspirates, 45.5% contained bacterial genomes. Most (80%) of bacterial DNA-positive cases contained DNA from the S mitis group. Previous arterial interventions were significantly associated with the occurrence of S mitis group DNA (P 1⁄4 .049, Fisher’s exact test). Conclusions: This is the first study to report the presence of bacterial DNA, predominantly of S mitis group origin, in the thrombus aspirates of surgical patients with lower limb arterial and deep venous thrombosis, suggesting their possible role in the pathogenesis of thrombotic events. Additional studies will, however, be needed to reach a final conclusion. (J Vasc Surg 2018;67:1902-7.) Clinical Relevance: This is the first study to report the presence of bacterial DNA, predominantly of Streptococcus mitis group origin, in the thrombus aspirates of patients with lower limb arterial and deep venous thrombosis. Interestingly, the occurrence of S mitis group DNA seems to be significantly associated with previous vascular manipulations. It remains to be established whether these findings play a role in the actual thrombosis. Bacterial inflammation has long been suggested to contribute to inflammation of atherosclerotic plaques, either directly or by indirect mechanisms, where inflammation at nonvascular sites can contribute to the progression of the lesions. Proposed bacteria include respiratory pathogens and periodontal bacteria as well as bacteria from the gastrointestinal tract. One group of common oral bacterial species, namely, Streptococcus mitis group, has been shown to have an exceptional ability to adhere to an endothelial surface and bind platelets as well. Previous studies showed that S mitis group DNA was predominant in thrombus aspirates from coronary arteries and cerebral arterial wall samples in patients with acute coronary events and cerebral aneurysms respectively. The S mitis group comprises 13 species. Most of these bacteria can be found in the oral cavity of healthy individuals. Based on these previous studies, it is likely that oral pathogens may play a certain role in the pathogenesis of cardiovascular diseases. To the best of our From the Division of Vascular Surgery, Department of Surgery, Fimlab Laboratories, Division of Interventional Radiology, Department of Radiology, and Science Centre, Tampere University Hospital; and the Department of Forensic Medicine, Department of Clinical Chemistry, and Department of Surgery, Faculty of Medicine and Life Sciences, University of Tampere. The study was financially supported by the Academy of Finland (grant no 286284 for T.L); Competitive State Research Financing of the Expert Responsibility area of Tampere University Hospital (grants X51001 and X51401); Finnish Foundation for Cardiovascular Research (T.L and PJK); Finnish Cultural Foundation; Tampere Tuberculosis Foundation (T.L and PJK); Viipuri Tuberculosis Foundation; Emil Aaltonen Foundation; Yrjö Jahnsson Foundation; Signe and Ane Gyllenberg Foundation; and Diabetes Research Foundation of Finnish Diabetes Association. Author conflict of interest: none. Correspondence: Damir Vakhitov, MD, Department of Surgery, PSHP, PL 2000, 33521, Tampere, Finland (e-mail: damir@fimnet.fi). The editors and reviewers of this article have no relevant financial relationships to disclose per the JVS policy that requires reviewers to decline review of any manuscript for which they may have a conflict of interest.