PLASMIN GENERATION IN HEALTHY INDIVIDUALS

Abstract

Introduction: The fibrinolytic system is important for fibrin clot remodeling and lysis, alterations in it can lead to bleeding disorders or thrombotic events. Plasmin is a central enzyme in this process, and its function is the cleavage of fibrin. The kinetics of plasmin generation (GP) and its inhibition during fibrinolysis have been poorly understood, as the assays to quantify these parameters are limited and poorly accessible. Recently, new methods of GP have emerged and with it, relevant information about the plasmin has been obtained from the clinical practice. In this context, studies has been shown association of increased GP with acute phase of thrombotic thrombocytopenic purpura disease, as well as association of decreased GP with obesity and cardiovascular disease. Until now, GP profile of healthy individuals has not yet been studied. Objective: assessing the capacity of healthy individuals in plasmin generation and its association with race, gender, age, weight, habits, lipid profile, renal profile, hepatic profile and inflammation. Material and methods: The study was conducted at the hemostasis laboratory of the blood center at UNICAMP. Samples from healthy individuals were collected between September 2020 and June 2023. A questionnaire was applied to acquire demographic data, medications in use and habits such as smoking and alcoholic beverages. For the assessment of plasmin generation capacity, five parameters were obtained: (1) Lag time LT-GP, (2) Maximum absorbance MA-GP, (3) Maximum velocity VM-GP, (4) Area under the curve AUC-GP, (5) Time to maximum velocity TVM-GP. Total cholesterol, LDL, HDL Triglycerides, blood glucose, creatinine, TGO, TGP and C-reactive protein were assessed. Statistical data were performed in SPSS software. Results and discussion: A total of 100 healthy individuals with a median age of 46 (19-73) were included in this study. The prevalence of white ethnicity was 77% while black was 23%. Although the literature shows significant differences between GP among African and European descendants, in this study this difference was not significant. Obesity classified by BMI had a median of 28 (17-48) and GP was not influenced by it. Interestingly, the age group over 60 years presented higher LT-GP (p = 0.009) compared to individuals between 18-30 years, and men presented lower MA-PG (p = 0.003), VM-PG (p = 0.011) and AUC-PG (p = 0.016) when compared to females. The association between plasmin generating capacity and male was confirmed by multivariate linear regression analysis in different applied models. Regarding Lipids, abnormal results was found in close 40% of individuals, however no association was found with GP. C-reactive protein test was abnormal in more than 50% of individuals and showed correlation with MA-PG, MV-PG and AUC-PG. Conclusions: Tests assessing the capacity of the fibrinolytic system are not yet accessible. New developments for GP has been shown promising results. For the first time, the GP profile and its association with demographic data and biochemical laboratory markers were evaluated in health individuals. Men have lower plasmin generating capacity compared to women and inflammatory indices such as C-reactive protein appear to contribute to plasmin modulation.