Acute inflammation in the uterine isthmus coincides with postpartum acute myometritis in the uterine body involving refractory postpartum hemorrhage of unknown etiology after cesarean delivery

Abstract

Uterine atony is a major cause of postpartum hemorrhage. We recently proposed the new histological concept of postpartum acute myometritis (PAM) for the pathophysiology of refractory uterine atony of unknown etiology, which is characterized by the diffuse activation of mast cells and the complement system as well as the massive infiltration of macrophages and neutrophils into the uterine body. We herein focused on the uterine isthmus just adjacent to the body. The isthmus becomes significantly elongated throughout pregnancy. It is composed of myocytes and fibroblasts with an extracellular matrix that forms a passive lower segment during labor. The aim of this study was to histologically examine the uterine isthmus in cases of PAM in the uterine body. Under the amniotic fluid embolism-registry program in Japan, we selected PAM cases from uterine samples obtained by cesarean hysterectomy and delivered to us for analyses between 2011 and 2017. Control tissues were collected during elective cesarean section. We investigated the isthmus tissues of these cases and performed immunohistochemistry for inflammatory cell markers, i.e. neutrophil elastase, mast cell tryptase, CD68, CD3, and C5a receptor (C5aR). The numbers of tryptase-positive degranulating mast cells, elastase-positive neutrophils, CD68-positive macrophages, and C5aR-positive cells in the isthmus were significantly higher in uteri with PAM in the body than in controls without PAM. CD3 was negative in both groups. In conclusion, inflammation and an anaphylactoid reaction were histologically detected not only in the uterine body, but in the isthmus among cases of refractory PPH of unknown etiology after cesarean section.