Monitoring of rivaroxaban levels in patients with class III obesity.

PURPOSE: There is little evidence to guide the use of direct oral anticoagulants (DOACs) in patients with class III obesity. Clinicians face the dilemma that using DOACs in patients with class III obesity may not provide adequate anticoagulation, while avoiding DOACs may deprive them of a useful therapeutic option. We present 2 cases describing our experience navigating rivaroxaban use in patients with class III obesity and review available case reports of measurement of rivaroxaban levels using a calibrated anti-factor Xa assay. SUMMARY: In patient case 1, the rivaroxaban trough level was within the reference range, and therapy was continued. In patient case 2, the rivaroxaban trough level was below the reference range, and the patient's anticoagulation therapy was switched to warfarin. No thromboembolic events were noted in the 2 patients more than 1 year (15 and 22 months, respectively) after initiation of anticoagulation therapy. Because of the many advantages associated with use of DOACs instead of vitamin K antagonists, further research is critical to enabling clinicians to use DOACs more confidently in a broader population. CONCLUSION: When monitoring rivaroxaban therapy in patients with class III obesity, there is uncertainty regarding clinical interpretation of drug levels that fall outside of established reference ranges, and monitoring is not standardized or widely available. In addition to case reports found in the literature, the presented cases highlight these challenges and differing clinical decisions made when evaluating rivaroxaban levels in patients with class III obesity.

Cardiac ischemia-reperfusion regulates sympathetic neuropeptide expression through gp130-dependent and independent mechanisms.

Cardiac function is regulated by a balance of sympathetic and parasympathetic transmission. Neuropeptide Y (NPY) and galanin (GAL) released from cardiac sympathetic neurons inhibits parasympathetic transmission in the heart. Sympathetic peptides may contribute to autonomic imbalance, which is characterized by increased sympathetic and decreased parasympathetic transmission and contributes to life threatening cardiovascular pathologies. Several gp130 cytokines are increased in the heart after myocardial infarction (MI), and these cytokines stimulate neuropeptide expression in sympathetic neurons. We used mice whose sympathetic neurons lack the gp130 receptor (gp130(DBH-Cre/lox) mice) to ask if cytokine activation of gp130 regulated neuropeptide expression in cardiac sympathetic nerves after MI. Myocardial infarction decreased NPY mRNA through a gp130 independent mechanism and increased VIP and PACAP mRNA via gp130, while GAL mRNA was unchanged. Immunohistochemistry revealed a gp130-dependent increase in PACAP38 in cells of the stellate ganglion after MI, and PACAP was detected in pre-ganglionic fibers of all genotypes and surgical groups. VIP was identified in a few sympathetic nerve fibers in all genotypes and surgical groups. GAL and PACAP38 were not detected in sham hearts, but peptide immunoreactivity was high in the infarct three days after MI. Surprisingly, peptides were abundant in cells that co-labeled with macrophage markers F4/80 and MAC2, but were not detected in sympathetic axons. PACAP protects cardiac myocytes from apoptosis, and GAL stimulates axon regeneration in addition to inhibiting parasympathetic transmission. Thus, these peptides may play an important role in cardiac and neuronal remodeling after ischemia-reperfusion.