Rivaroxaban attenuates neutrophil maturation in the bone marrow niche.

Pharmacological inhibition of factor Xa by rivaroxaban has been shown to mediate cardioprotection and is frequently used in patients with, e.g., atrial fibrillation. Rivaroxaban's anti-inflammatory actions are well known, but the underlying mechanisms are still incompletely understood. To date, no study has focused on the effects of rivaroxaban on the bone marrow (BM), despite growing evidence that the BM and its activation are of major importance in the development/progression of cardiovascular disease. Thus, we examined the impact of rivaroxaban on BM composition under homeostatic conditions and in response to a major cardiovascular event. Rivaroxaban treatment of mice for 7 days markedly diminished mature leukocytes in the BM. While apoptosis of BM-derived mature myeloid leukocytes was unaffected, lineage-negative BM cells exhibited a differentiation arrest at the level of granulocyte-monocyte progenitors, specifically affecting neutrophil maturation via downregulation of the transcription factors Spi1 and Csfr1. To assess whether this persists also in situations of increased leukocyte demand, mice were subjected to cardiac ischemia/reperfusion injury (I/R): 7 d pretreatment with rivaroxaban led to reduced cardiac inflammation 72 h after I/R and lowered circulating leukocyte numbers. However, BM myelopoiesis showed a rescue of the leukocyte differentiation arrest, indicating that rivaroxaban's inhibitory effects are restricted to homeostatic conditions and are mainly abolished during emergency hematopoiesis. In translation, ST-elevation MI patients treated with rivaroxaban also exhibited reduced circulating leukocyte numbers. In conclusion, we demonstrate that rivaroxaban attenuates neutrophil maturation in the BM, which may offer a therapeutic option to limit overshooting of the immune response after I/R.

Risk Factors Associated with In-Hospital Mortality for Patients with Acute Abdomen After Cardiac Surgery.

OBJECTIVES: Management of acute abdomen (AA) differs due to the heterogeneity of underlying pathophysiology. Complications of AA and its overall outcome after cardiac surgery are known to be associated with poor results. The aim of this retrospective analysis was to evaluate risk factors for AA in patients undergoing cardiac surgery. METHODS: Between December 2011 and December 2014, a total of 131 patients with AA after cardiac surgery were identified and retrospectively analyzed using our institutional database. Statistical analysis of risk factors concerning in-hospital mortality of mentioned patient cohort was performed using IBM SPSS Statistics. RESULTS: Overall in-hospital mortality was 54.2% (71/131). Analyzing in-hospital non-survivors (NS) versus in-hospital survivors (S) peripheral artery disease (28.2% vs. 11.7%; p = 0.03), the need for assist device therapy (33.8% vs. 16.7%; p = 0.03) and the requirement of hemodialysis (67.6% vs. 23.3%; p < 0.01) were significantly higher in NS. Furthermore, lactic acid values at onset of symptoms were shown to be significantly higher in NS (5.7 ± 5.7 mmol/L vs. 2.8 ± 2.9 mmol/L; p < 0.01). Assured diagnosis of mesenterial ischemia was strongly associated with worse outcome (odds ratio 10.800, 95% confidence interval 2.003-58.224; p = 0.006). CONCLUSION: In conclusion, in critically ill patients after performed cardiac surgery peripheral vascular disease, need for supportive hemodynamic assist device systems and occurrence of renal failure are risk factors associated with worsen outcome. Additionally, rise of lactic acid could potentially be associated with onset of intestinal malperfusion and should be taken into account in therapeutic decisions preventing fatal mesenterial ischemia.