Anti-Plasminogen monoclonal antibody, clone BNQH-9131

Background: Deep sternal wound problems (DSWP) are a rare, but serious complication following cardiac surgery requiring extensive medical treatment and resulting in increased mortality. Cardiac surgery patients presenting with both obesity and diabetes mellitus type 2 (DM 2) showed an increased incidence of DSWP in our clinic. As platelets upon activation have been shown to excrete growth factors and attractants for tissue stem cells, thus potentially promoting tissue healing, we investigated whether activated platelets could reduce the incidence of DSWP. Methods: We applied activated autologous platelet rich plasma (PRP), forming a gel (PLG), between the sternal halves immediately prior to closure in obese [body mass index (BMI) >30] DM 2 cardiac surgery patients. The reference group constituted of all elective patients with a BMI >30 and DM 2 operated upon in the 2-year period before the application of PLG. Results: The PLG treated group (n=144) showed a significant decrease in DSWP compared to the reference group (n=118), 6 DSWP vs. 13 DSWP respectively, P=0.03. In these groups the application of PLG was associated with a risk reduction for DSWP from 11% to 4.2%. Conclusions: These results suggest PLG application could be beneficial to prevent DSWP following cardiac surgery in a high-risk population.

The antifibrinolytic agent, tranexamic acid (TXA), an inhibitor of plasmin formation, currently is evaluated to reduce bleeding in various conditions, including traumatic brain injury (TBI). Because plasmin is implicated in inflammation and immunity, we investigated the effects of plasmin inhibition on the immune response after TBI in the presence or absence of induced pneumonia. Wild-type mice treated with vehicle or TXA or mice deficient in plasminogen (plg(-/-)) underwent TBI using the controlled cortical impact model. Mice were then subjected to Staphylococcus aureus induced pneumonia and the degree of immune competence determined. Significant baseline changes in the innate immune cell profile were seen in plg(-/-) mice with increases in spleen weight and white blood cell counts, and elevation in plasma interleukin-6 levels. The plg(-/-) mice subjected to TBI displayed no additional changes in these parameters at the 72 h or one week time point post-TBI. The plg(-/-) mice subjected to TBI did not exhibit any further increase in susceptibility to endogenous infection. Pneumonia was induced by intratracheal instillation of S. aureus. The TBI did not worsen pneumonia symptoms or delay recovery in plg(-/-) mice. Similarly, in wild type mice, treatment with TXA did not impact on the ability of mice to counteract pneumonia after TBI. Administration of TXA after TBI and subsequent pneumonia, however, altered the number and surface marker expression of several myeloid and lymphoid cell populations, consistent with enhanced immune activation at the 72 h time point. This investigation confirms the immune-modulatory properties of TXA, thereby highlighting its effects unrelated to inhibition of fibrinolysis.