[Changes in Prescription Patterns of Oral Anticoagulants in Family Practices after Marketing Approval of Direct Oral Anticoagulants]. / Änderungen bei der Verordnung oraler Antikoagulation in Hausarztpraxen nach Einführung der direkten oralen Antikoagulanzien.

AIM OF THE STUDY: Since 2011, non-vitamin-K-dependent oral anticoagulants (NOAC) have extended the spectrum of anticoagulation therapy. Initially, the approval of NOAC was limited to the prophylaxis of postoperative thrombosis, but in the course of time the spectrum was extended to the therapy of thrombosis and embolism as well as anticoagulation in non-valvular atrial fibrillation. The study was designed to examine how the approval of NOAC had affected the prescribing behaviour of general practitioners in the first years of their approval. METHODS: In a retrospective longitudinal study, the prescriptions of anticoagulants between 2012 and 2017 were analysed in 3 general practitioners' practices in the Bonn area. The study included all patients for whom at least one prescription from a NOAC or a vitamin K antagonist (VKA) was documented in the administrative system of the practices during this period. RESULTS: A total of n=579 patient files were evaluated (47% female; median age 75 years). Of these, 47% received a VKA, and 40% a NOAC (59% rivaroxaban, 29% apixaban, 9% dabigatran and 3% edoxaban). During the period under examination, the share of VKA prescriptions decreased from 45% to 14% and the share of NOAC increased from 28% to 87%. Anti-coagulation was changed in 12%. The most frequent change was from a VKA to a NOAC (70%). CONCLUSION: After marketing approval, the use of NOAC in the initial prescriptions increased steadily. This trend can also be seen in other European studies. VKA are mainly prescribed to patients with stable oral anticoagulation. As recommended in the guidelines, anticoagulation is changed mainly when problems occur during therapy. If the trend in the prescription of anticoagulants continues, in the medium term, VKA will only be prescribed for patients who have been stable for many years and for patients with artificial heart valves.

Steroid hormone bioavailability is controlled by the lymphatic system.

The steroid hormone progesterone accounts for immune tolerance in pregnancy. Enhanced progesterone metabolism to 6α-OH-pregnanolone occurs in complicated pregnancies such as in preeclampsia with preterm delivery or intrauterine growth restriction, and in cancer. As lymphatic endothelial cells (LECs) promote tumor immunity, we hypothesized that human LECs modify progesterone bioavailability. Primary human LECs and mice lymph nodes were incubated with progesterone and progesterone metabolism was analyzed by thin layer chromatography and liquid chromatography-mass spectrometry. Expression of steroidogenic enzymes, down-stream signal and steroid hormone receptors was assessed by Real-time PCR. The placental cell line HTR-8/SV neo was used as reference. The impact of the progesterone metabolites of interest was investigated on the immune system by fluorescence-activated cell sorting analysis. LECs metabolize progesterone to 6α-OH-pregnanolone and reactivate progesterone from a precursor. LECs highly express 17ß-hydroxysteroid dehydrogenase 2 and are therefore antiandrogenic and antiestrogenic. LECs express several steroid hormone receptors and PIBF1. Progesterone and its metabolites reduced TNF-α and IFN-γ production in CD4+ and CD8+ T cells. LECs modify progesterone bioavailability and are a target of steroid hormones. Given the global area represented by LECs, they might have a critical immunomodulatory control in pregnancy and cancer.