Abstract Number: PB0117
Meeting: ISTH 2021 Congress
Background: Geographic variability in thrombosis incidence and coagulation and fibrinolysis potential are poorly understood.
Aims: The aim of the present study was to evaluate thrombin (TG) and plasmin generation (PG) potential in healthy Tanzanians compared with healthy individuals of Western-European ancestry and to assess the effects of environmental, genetic and non-genetic host factors.
Methods: We used data from the 300-Tanzania-FG (n=313) and the Dutch 500FG cohort (n=392), in which TG and PG were measured using modified calibrated automated thrombography. We determined associations of TG and PG with cohort characteristics and inflammatory mediators, and the impact of genetic variations through a genome-wide association study in both cohorts. Seasonal dietary influence on TG and PG was assessed using food metabolome data in Tanzanians.
Tanzanians exhibited enhanced TG, PG, and TG/PG ratio compared with Dutch participants, and an increased normalized thrombomodulin sensitivity ratio, suggesting reduced sensitivity to the anticoagulant actions of protein C (Figure.1A). Female sex, BMI and age were associated with TG and PG in both cohorts. TG and PG in Tanzanians were also associated with food-derived plasma metabolites. The Tanzanians had higher concentrations of pro-inflammatory cytokines, which correlated strongly with TG and PG (Figure.1B). There was limited overlap in genetic variation associated with TG and PG between both cohorts (Figure.2A). Pathway analysis in the Tanzanian cohorts revealed multiple immune pathways that were enriched with TG and PG traits (Figure.2B), confirming the importance of coregulation of coagulation and inflammation.
Conclusions: Collectively, we show that Tanzanians have enhanced TG and PG potential relative to people of Western-European, which relates to a pro-inflammatory status and different genetic regulation. Also, increased TG/PG ratio as well as reduced sensitivity to protein C activation indicates a hypercoagulable tendency. These findings are important in view of geographic variability in thrombosis and the rapid increase in non-communicable diseases in sub-Saharan Africa.
To cite this abstract in AMA style:Temba GS, Vadaq N, Wan J, Kullaya V, Huskens D, Pecht T, Jaeger M, Boahen CK, Matzaraki V, Broeders W, Joosten L, de Groot PG, Schultze J, van der Ven AJ, Kumar V, Mmbaga BT, de Laat B, Netea MG, Roest M, de Mast Q. Differences in Thrombin and Plasmin Generation Potential between East African and Western European Adults: The Role of Genetic and Non-genetic Factors [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 1). https://abstracts.isth.org/abstract/differences-in-thrombin-and-plasmin-generation-potential-between-east-african-and-western-european-adults-the-role-of-genetic-and-non-genetic-factors/. Accessed September 24, 2021.
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