RESUMEN
The issue of how to identify newly diagnosed multiple myeloma (NDMM) patients requiring thromboprophylaxis remains unsolved. Several changes in thrombin generation (TG)-derived parameters have been described in multiple myeloma (MM) patients recently. Assessment of prothrombotic risk with a fully automated TG analyzer could reduce interlaboratory variability. Our objective was to determine whether ST-Genesia® could reveal a hypercoagulable state in NDMM compared to healthy controls. We conducted a multicenter observational study of NDMM requiring initial treatment to compare TG parameters obtained with ST-Genesia® analyzer and ST-ThromboScreen® reagent with a control group. Clinical data were obtained from medical records and blood samples were collected before initial anti-myeloma therapy. A thrombophilia panel was performed in all patients. Compared to age- and sex-matched controls (n = 83), NDMM patients (n = 83) had significantly higher peak height, higher velocity index, shorter time-to-peak and lower percentage of endogenous thrombin potential (ETP) inhibition after adding thrombomodulin (TM) (ETP%inh). NDMM on prophylactic low molecular weight heparin (LMWH) showed reduced both peak height and velocity index compared to NDMM who had not yet started VTE prophylaxis, similar to that of controls. Moreover, partial correction of ETP%inh was observed in MM patients on LMWH. The presence of a thrombophilia did not modify the TG phenotype. Untreated NDMM patients showed an enhanced TG, regardless of their thrombophilia status. They generate a higher peak of thrombin, take less time to produce it, and exhibit resistance to TM inhibition. Our findings suggest that standard prophylactic dose of LMWH may reduce TG at levels of healthy controls.
Asunto(s)
Mieloma Múltiple , Trombofilia , Tromboembolia Venosa , Humanos , Trombina , Mieloma Múltiple/tratamiento farmacológico , Anticoagulantes/uso terapéutico , Heparina de Bajo-Peso-Molecular/uso terapéutico , Tromboembolia Venosa/tratamiento farmacológico , Trombofilia/diagnóstico , Trombofilia/etiología , Trombofilia/tratamiento farmacológico , Pruebas de Coagulación SanguíneaRESUMEN
Quercus suber L. is a forest tree with remarkable ecological, social and economic value in the southern Europe ecosystems. To circumvent the difficulties of breeding such long-lived species like Q. suber in a conventional fashion, clonal propagation of Q. suber elite trees can be carried out, although this process is sometimes unsuccessful. To help decipher the complex program underlying the development of Q. suber somatic embryos from the first early stage until maturity, a proteomic approach based on DIGE and MALDI-MS has been envisaged. Results highlighted several key processes involved in the three developmental stages (proliferative, cotyledonary and mature) of Q. suber somatic embryogenesis studied. Results show that the proliferation stage is characterized by fermentation as an alternative energy source at the first steps of somatic embryo development, as well as by up-regulation of proteins involved in cell division. In this stage reactive oxygen species play a role in proliferation, while other proteins like CAD and PR5 seem to be implied in embryonic competence. In the transition to the cotyledonary stage diverse ROS detoxification enzymes are activated and reserve products (mainly carbohydrates and proteins) are accumulated, whereas energy production is increased probably to participate in the synthesis of primary metabolites such as amino acids and fatty acids. Finally, in the mature stage ethylene accumulation regulates embryo development. BIOLOGICAL SIGNIFICANCE: Quercus suber L. is a forest tree with remarkable ecological, social and economic value in the southern Europe ecosystems. To circumvent the difficulties of breeding such long-lived species like Q. suber in a conventional fashion, clonal propagation of Q. suber elite trees can be carried out, although this process is sometimes unsuccessful. To help decipher the complex program underlying the development of Q. suber somatic embryos from the first early stage until maturity, in deep studies become necessary. This article is part of a Special Issue entitled: Translational Plant Proteomics.