Blood: EPCR defects or EPCR antibodies prevent haemophilia joint disease

Recently, researchers found that the combination of the coagulation factor VIIa (FVIIa) in combination with the endothelial cell protein C receptor (EPCR) induces anti-inflammatory signals and protects the integrity of the vascular barrierInflammation and vascular permeability are considered to be the main factors in the occurrence of hemophilia joint diseasethis study aims to explore the potential role of FVIIa and EPCR interactions in haemophilia pathogenesis and rFVIIa treatmentTo do this, the researchers first bred mice with haemophiliac A (FVIII---)that lackep EPCR (EPCR-/-FVIII-/-) or over-express EPCR (EPCR-FVIII-/--)Induced joint bleeding is induced by needle damage to FVIII-/-, EPCR-/-FVIII-/-and EPCR-FVIII-/-mouseHemophilia-based sliding diaphragm was evaluated by monitoring joint bleeding, joint diameter changes and pathological analysis of joint tissue slicesFVIII-/-mouse, EPCR defectcane can significantly reduce the severity of haemophilia semenitisEPCR defects reduce IL-6 secretion, macrophage leaching and new angiogenesis in the slip membrane after joint bleedingSingle dose rFVIIa is sufficient to completely prevent the occurrence of mild haemophilia semenitis in EPCR-/-FVIII-/-mouseThere was no significant difference between EPCR high-expression FVIII-/-mouse hemophilia joint disease in fVIII-/-mice, and 3 doses of rFVIIa had partial protective effects on haemophilia semenitis in these miceConsistent with the data of EPCR defect sepsis preventable, single-dose EPCR blocking monoclonal antibody can significantly reduce joint bleeding fVIII-/-mouse hemophilia gliomydiais, this study suggests that EPCR may be an attractive new target for preventing joint damage in haemophiliacs