OBJECTIVES: Given the efficacy and safety of recombinant human activated protein C (rhAPC) in the systemic inflammatory response syndrome, this study was designed to review the evidence for a role for APC in the pathogenesis of preeclampsia. Preeclampsia is a proinflammatory and procoagulant state, and it is a pregnancy-specific condition that mimics the systemic inflammatory response syndrome. rhAPC reduces mortality in patients with systemic inflammatory response syndrome and could potentially have a role as disease-modifying therapy in preeclampsia. To determine which patients would be offered rhAPC, the literature pertaining to fetal/neonatal outcomes for preeclampsia remote from term, transplacental transport of protein C, and pregnancy experience with the compound were reviewed. DATA SOURCES: MEDLINE, review papers, hand searches of relevant nonindexed journals, and the bibliographies of relevant textbooks and articles reviewed. STUDY SELECTION: Randomized controlled trials were considered to provide the best quality of clinical data. Case-control series were considered over uncontrolled data. Some data were not available in the published literature (e.g., neonatal outcomes at various gestational ages and birthweights after a hypertensive pregnancy; and transplacental transfer of protein C), and these data were determined by us. DATA EXTRACTION: Data were extracted by systematic review onto data collection sheets. Because of the quality of the data, this review is primarily qualitative. DATA SYNTHESIS: APC levels fall during normal gestation, returning to normal values by 6 wks postpartum. Limited data suggest that early onset preeclampsia is a state of further, and inappropriate, reduction in APC. Preeclampsia resembles systemic inflammatory response syndrome in this regard. After hypertensive pregnancies, neonates have a 50% chance of intact survival if delivered after 27 + 0 wks of gestation with a birthweight of >600 g. It would seem ethical to offer women with preeclampsia with <50% chance of intact perinatal survival novel and potentially disease-modifying therapy such as rhAPC, especially as there is no transplacental transfer of protein C. Limited evidence would support the use of rhAPC in women with severe postpartum preeclampsia. CONCLUSIONS: Sufficient data exist to support the use of rhAPC in phase II clinical studies for women with either early onset preeclampsia or severe or deteriorating postpartum disease.
RCT Entities:
OBJECTIVES: Given the efficacy and safety of recombinant human activated protein C (rhAPC) in the systemic inflammatory response syndrome, this study was designed to review the evidence for a role for APC in the pathogenesis of preeclampsia. Preeclampsia is a proinflammatory and procoagulant state, and it is a pregnancy-specific condition that mimics the systemic inflammatory response syndrome. rhAPC reduces mortality in patients with systemic inflammatory response syndrome and could potentially have a role as disease-modifying therapy in preeclampsia. To determine which patients would be offered rhAPC, the literature pertaining to fetal/neonatal outcomes for preeclampsia remote from term, transplacental transport of protein C, and pregnancy experience with the compound were reviewed. DATA SOURCES: MEDLINE, review papers, hand searches of relevant nonindexed journals, and the bibliographies of relevant textbooks and articles reviewed. STUDY SELECTION: Randomized controlled trials were considered to provide the best quality of clinical data. Case-control series were considered over uncontrolled data. Some data were not available in the published literature (e.g., neonatal outcomes at various gestational ages and birthweights after a hypertensive pregnancy; and transplacental transfer of protein C), and these data were determined by us. DATA EXTRACTION: Data were extracted by systematic review onto data collection sheets. Because of the quality of the data, this review is primarily qualitative. DATA SYNTHESIS: APC levels fall during normal gestation, returning to normal values by 6 wks postpartum. Limited data suggest that early onset preeclampsia is a state of further, and inappropriate, reduction in APC. Preeclampsia resembles systemic inflammatory response syndrome in this regard. After hypertensive pregnancies, neonates have a 50% chance of intact survival if delivered after 27 + 0 wks of gestation with a birthweight of >600 g. It would seem ethical to offer women with preeclampsia with <50% chance of intact perinatal survival novel and potentially disease-modifying therapy such as rhAPC, especially as there is no transplacental transfer of protein C. Limited evidence would support the use of rhAPC in women with severe postpartum preeclampsia. CONCLUSIONS: Sufficient data exist to support the use of rhAPC in phase II clinical studies for women with either early onset preeclampsia or severe or deteriorating postpartum disease.
Authors: John Allotey; Nadine Marlin; Ben W Mol; Peter Von Dadelszen; Wessel Ganzevoort; Joost Akkermans; Asif Ahmed; Jane Daniels; Jon Deeks; Khaled Ismail; Ann Marie Barnard; Julie Dodds; Sally Kerry; Carl Moons; Khalid S Khan; Richard D Riley; Shakila Thangaratinam Journal: Diagn Progn Res Date: 2017-02-20
Authors: Peter von Dadelszen; François Audibert; Emmanuel Bujold; Jeffrey N Bone; Ash Sandhu; Jing Li; Chirag Kariya; Youkee Chung; Tang Lee; Kelvin Au; M Amanda Skoll; Marianne Vidler; Laura A Magee; Bruno Piedboeuf; Philip N Baker; Sayrin Lalji; Kenneth I Lim Journal: BMC Res Notes Date: 2022-07-07