Plasma fibrin clot proteomics in healthy subjects: Relation to clot permeability and lysis time

Background: Little is known about fibrin clot composition in relation to its structure and lysability. We investigated plasma clots protein composition and its associations with clot properties. Methods: We studied 20 healthy subjects aged 31-49 years in whom plasma fibrin clot permeability (K-s) and clot lysis time (CLT) were determined. A proteomic analysis of plasma fibrin clots was based on quantitative liquid chromatography-mass spectrometry. Results: Among 494 clot-bound proteins identified in all clots, the highest concentrations were for fibrinogen chains (about 64% of the clot mass) and fibronectin (13%). alpha(2)-antiplasmin (2.7%), factor XIIIA (1.2%), complement component C3 (1.2%), and histidine-rich glycoprotein (HRG, 0.61%) were present at relatively high concentrations. Proteins present in concentrations < 0.5% included (pro)thrombin, plasminogen, apolipoproteins, or platelet factor 4 (PF4). Fibrinogen-alpha and -gamma chains were associated with age, while body-mass index with clot-bound apolipoproteins (all p <.05). K-s correlated with fibrinogen-gamma and PF4 amounts within plasma clots. CLT was associated with fibrinogen-alpha and -gamma, PF4, and HRG (all p <.05). Conclusions: This study is the first to show associations of two key measures of clot properties with protein content within plasma clots, suggesting that looser fibrin clots with enhanced lysability contain less fibrinogen-gamma chain, platelet-derived PF4, and HRG. Significance: Our study for the first time suggests that more permeable fibrin clots with enhanced lysability contain less fibrinogen-gamma chain, platelet-derived factor 4, and histidine-rich glycoprotein, which is related to accelerated clot lysis. The current findings might have functional consequences regarding clot structure, stability, and propagation of thrombin generation, and detailed proteomic analysis of clots in various disorders opens new perspective for coagulation and fibrin research.