Abstract: The invention relates to materials and procedures for identifying or using tissue factor (TF) pre-mRNA splicing, Clk 1 activity or TF-dependent coagulation in platelet cells for the diagnosis, prognosis, or prediction of a disease or disorder associated with disordered coagulation. Since activated platelets splice pre-mRNAs to generate inflammatory and thrombotic mediators that contribute to diseases such as sepsis and septic shock, (TF) pre-mRNA splicing in platelets is an indicator of inflammatory and thrombotic disease states. TF pre-mRNA splicing in platelets is correlated with sepsis, increased age (?65), APACHE II score, and bacteremia. Thus, TF snRNA expression patterns in platelets may be used for the diagnosis, prognosis, or prediction of a disease or disorder associated with disordered coagulation, for example, patients that are at a higher risk for severe sepsis, organ failure, and death.

Abstract: Platelets are induced to proliferate, form extensions and produce daughter cells by various methods, including culturing platelets under thrombocytopenic conditions. Expansion of platelet cell numbers increases the storage life of platelets. Modulation of RT activity can be used to produce new daughter platelets. Therefore, the invention provides a new therapeutic use for RT inhibitors that can now be used for treatment of thrombocytopenia and related disorders. Likewise, application of soluble protein factor that may be secreted and/or released by platelets cultured under thrombocytopenic conditions may also be used as a therapeutic agent to increase platelet numbers.

Abstract: The invention relates to materials and procedures for identifying or using tissue factor (TF) pre-mRNA splicing, CIk 1 activity or TF-dependent coagulation in platelet cells for the diagnosis, prognosis, or prediction of a disease or disorder associated with disordered coagulation. Since activated platelets splice pre-mRNAs to generate inflammatory and thrombotic mediators that contribute to diseases such as sepsis and septic shock, (TF) pre-mRNA splicing in platelets is an indicator of inflammatory and thrombotic disease states. TF pre-mRNA splicing in platelets is correlated with sepsis, increased age (?65), APACHE II score, and bacteremia. Thus, TF mRNA expression patterns in platelets may be used for the diagnosis, prognosis, or prediction of a disease or disorder associated with disordered coagulation, for example, patients that are at a higher risk for severe sepsis, organ failure, and death.

Abstract: The invention relates to therapeutic target recognition, development, and validation of a compound capable of directly or indirectly modulating TF pre-mRNA splicing in a platelet cell and the use of a platelet TF pre-mRNA splicing modulator for the treatment of a subject suffering from, or thought to be suffering from, disordered coagulation.