title: Clot lysis time in platelet-rich plasma: method assessment, comparison with assays in platelet-free and platelet-poor plasmas, and response to tranexamic acid.
abstract: Fibrinolysis dysfunctions cause bleeding or predisposition to thrombosis. Platelets contain several factors of the fibrinolytic system, which could up or down regulate this process. However, the temporal relationship and relative contributions of plasma and platelet components in clot lysis are mostly unknown. We developed a clot lysis time (CLT) assay in platelet-rich plasma (PRP-CLT, with and without stimulation) and compared it to a similar one in platelet-free plasma (PFP) and to another previously reported test in platelet-poor plasma (PPP). We also studied the differential effects of a single dose of tranexamic acid (TXA) on these tests in healthy subjects. PFP- and PPP-CLT were significantly shorter than PRP-CLT, and the three assays were highly correlated (p < 0.0001). PFP- and PPP-, but more significantly PRP-CLT, were positively correlated with age and plasma PAI-1, von Willebrand factor, fibrinogen, LDL-cholesterol, and triglycerides (p < 0.001). All these CLT assays had no significant correlations with platelet aggregation/secretion, platelet counts, and pro-coagulant tests to explore factor X activation by platelets, PRP clotting time, and thrombin generation in PRP. Among all the studied variables, PFP-CLT was independently associated with plasma PAI-1, LDL-cholesterol, and triglycerides and, additionally, stimulated PRP-CLT was also independently associated with plasma fibrinogen. A single 1 g dose of TXA strikingly prolonged all three CLTs, but in contrast to the results without the drug, the lysis times were substantially shorter in non-stimulated or stimulated PRP than in PFP and PPP. This standardized PRP-CLT may become a useful tool to study the role of platelets in clot resistance and lysis. Our results suggest that initially, the platelets enmeshed in the clot slow down the fibrinolysis process. However, the increased clot resistance to lysis induced by TXA is overcome earlier in platelet-rich clots than in PFP or PPP clots. This is likely explained by the display of platelet pro-fibrinolytic effects. Focused research is needed to disclose the mechanisms for the relationship between CLT and plasma cholesterol and its potential pathophysiologic and clinical relevance.
authors.affiliation: Department of Hematology-Oncology, School of Medicine, P. Catholic University of Chile, Santiago, Chile.
authors.forename: Olga
authors.initials: O
authors.lastname: Panes
authors.forename: Oslando
authors.initials: O
authors.lastname: Padilla
authors.forename: Valeria
authors.initials: V
authors.lastname: Matus
authors.forename: Claudia G
authors.initials: CG
authors.lastname: Sáez
authors.forename: Alejandro
authors.initials: A
authors.lastname: Berkovits
authors.forename: Jaime
authors.initials: J
authors.lastname: Pereira
authors.forename: Diego
authors.initials: D
authors.lastname: Mezzano
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000933:Antifibrinolytic Agents / Q000494:pharmacology*; D001792:Blood Platelets / Q000378:metabolism*; D001798:Blood Proteins / Q000378:metabolism; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010949:Plasma; D010979:Platelet Function Tests / Q000379:methods; D013997:Time Factors; D014148:Tranexamic Acid / Q000494:pharmacology*; D014280:Triglycerides / Q000378:metabolism
chemical_list: D000933:Antifibrinolytic Agents; D001798:Blood Proteins; D014280:Triglycerides; D014148:Tranexamic Acid