Complement C3a expression and tryptase degranulation as promising histopathological tests for diagnosing fatal amniotic fluid embolism

To date, the most recent specific diagnostic investigations for amniotic fluid embolism have been unable to conclusively identify any mechanism of disease other than a physical block to the circulation. We selected eight fatal cases in previously healthy women with uneventful singleton term pregnancies who presented to tertiary care centers in Italy for delivery. Pathologic features were assessed immunohistochemically using anti-fibrinogen, anti-tryptase, anti-C3a, and anti-cytokeratin antibodies. AE1/AE3 cytokeratin stains proved positive, and tryptase-positive material was documented outside pulmonary mast cells. In all studied cases, expression of complement C3a was twofold lower than in the control group, suggesting a possible complement activation in AFE, initiated by fetal antigen leaking into the maternal circulation.