Browsing by Author "Matus, Valeria"

Now showing 1 - 3 of 3
  • Thumbnail Image
    Item
    Clot lysis time in platelet-rich plasma: Method assessment, comparison with assays in platelet-free and platelet-poor plasmas, and response to tranexamic acid
    (TAYLOR & FRANCIS INC, 2012) Panes, Olga; Padilla, Oslando; Matus, Valeria; Saez, Claudia G.; Berkovits, Alejandro; Pereira, Jaime; Mezzano, Diego
    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.
  • Thumbnail Image
    Item
    Human platelets synthesize and express functional tissue factor
    (AMER SOC HEMATOLOGY, 2007) Panes, Olga; Matus, Valeria; Saez, Claudia G.; Quiroga, Teresa; Pereira, Jaime; Mezzano, Diego
    The source and significance of bloodborne tissue factor (TF) are controversial. TF mRNA, protein, and TF-dependent procoagulant activity (PCA) have been detected in human platelets, but direct evidence of TF synthesis is missing. Nonstimulated monocyte-free platelets from most patients expressed TF mRNA, which was enhanced or induced in all of them after platelet activation. Immunoprecipitation assays revealed TF protein (mainly of a molecular weight [Mr] of approximately 47 kDa, with other bands of approximately 35 and approximately 60 kDa) in nonstimulated platelet membranes, which also increased after activation. This enhancement was concomitant with TF translocation to the plasma membrane, as demonstrated by immunofluorescence-confocal microscopy and biotinylation of membrane proteins. Platelet PCA, assessed by factor Xa (FXa) generation, was induced after activation and was inhibited by 48% and 76% with anti-TF and anti-FVIIa, respectively, but not by intrinsic pathway inhibitors. Platelets incorporated [35S]-methionine into TF proteins with Mr of approximately 47 kDa, approximately 35 kDa, and approximately 60 kDa, more intensely after activation. Puromycin but not actinomycin D or DRB (5,6-dichloro-1 -beta-D-ribofuranosylbenzimidazole)inhibited TIF neosynthesis. Thus, human platelets not only assemble the clotting reactions on their membrane, but also supply their own TIF for thrombin generation in a timely and spatially circumscribed process. These observations simplify, unify, and provide a more coherent formulation of the current cellbased model of hemostasis.
  • Thumbnail Image
    Item
    Procarboxypeptidase U (TAFI) and the Thr325Ile proCPU polymorphism in patients with hereditary mucocutaneous hemorrhages
    (ELSEVIER, 2009) Matus, Valeria; Willemse, Johan; Quiroga, Teresa; Goycoolea, Manuela; Aranda, Eduardo; Panes, Olga; Pereira, Jaime; Hendriks, Dirk; Mezzano, Diego
    Background: Patients with hereditary mucocutaneous bleeding are difficult to diagnose and many of them fulfill the category of bleeders of unknown cause (BUC). The pathogenic role of hyperfibrinolysis has received little attention, despite the successful use of antifibrinolytic drugs in treating many of these patients. Theoretically, decreased plasma procarboxypeptidase U (proCPU) levels or lower carboxypeptidase U (CPU) stability would result in higher fibrinolytic activity and bleeding tendency.