The Core B hematology and coagulation core facility will support the proposed project aims to address the central hypothesis of the program project: Protein glycosylation and glycoprotein remodeling modulate the coagulopathy and inflammation of sepsis. Core B will analyze blood samples from healthy mice and mice undergoing sepsis or SIRS, and healthy human volunteers and patients with sepsis or SIRS to support project aims. Core B will use a predefined combination of screening and specific assays to detect significant changes in experimental versus control studies, in particular those changes related to the coagulation abnormalities and coagulopathy of sepsis. Core B will complete hematology analyses to assess bleeding, platelet count, other changes in cellular blood components. Freshly isolated whole blood samples will be subjected to complete blood count (CBC) including red cell indexes, platelet count, and white blood cell differential count. Giemsa stained smears of representative samples are also prepared and reviewed to assess blood cell morphology. These tests provide a sensitive assessment of the hematopoietic system and coagulation abnormalities related to the presence of coagulopathy. Core B will also complete a serum chemistry panel to assess basic metabolism and organ damage by measuring blood concentrations of bicarbonate, chloride, sodium, potassium, calcium, phosphorus, total protein, albumin, total bilirubin, glucose, BUN, creatinine, AST (SGOT), ALT (SGPT), alkaline phosphatase, and lipids to evaluate the overall functions of the liver, pancreas, kidney, as well as general electrolytes and metabolic status. Core B will further assess changes in the four components of hemostasis. To detect possible changes related to the presence of coagulopathy, a panel of assays will be performed on all mice and human plasma samples including von Willebrand antigen (primary hemostasis), PT, APTT, clotting factors II, V, VII, VIII, IX, X, XI and XII, fibrinogen, and D-dimer or FDPs (coagulation), protein C, protein S, and antithrombin (anticoagulation), and antiplasmin (fibrinolysis). Also available if requested by project researchers are tests for plasma tissue factor (TF), tissue factor pathway inhibitor (TFPI), and whole blood thromboelastographs (TEG). These screening assays will provide an efficient and comprehensive approach to detect significant deviations from normal, and are expected to assist project researchers in achieving the proposed aims of this program. The data acquired by Core B will aid project researchers in identifying, characterizing, and comparing disease mechanisms that involve coagulation abnormalities in sepsis due to Gram-negative and Gram-positive bacterial pathogens, and the underlying Systemic Inflammatory Response Syndrome.
This core facility supports multiple research projects investigating recent discoveries pertaining to the pathogenesis of sepsis, which is a frequently lethal syndrome each year afflicting millions of people in the U.S. and costing many billions of dollars in health care. Support provided by this core facility will help the research projects obtain their goals focused on gaining a greater understanding of the host inflammation and coagulopathy of sepsis and identifying novel potentially more effective therapeutic approaches.
