To cite this article: Hulstein JJJ, van Runnard Heimel PJ, Franx A, Lenting PJ, Bruinse HW, Silence K, de Groot PhG, Fijnheer R. Acute activation of the endothelium results in increased levels of active von Willebrand factor in hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome. 2006; 4: 2569-75. Summary. Background: HELLP (hemolysis, elevated liver enzymes and low platelets) syndrome is a severe complication of pre-eclampsia in pregnancy, characterized by microvascular platelet thrombi. Activation of the endothelium is thought to play a key role in pre-eclampsia and HELLP syndrome. Activation of endothelial cells may lead to release of von Willebrand factor (VWF) multimers, which are highly reactive with platelets. Normally, newly released multimers are cleaved by ADAMTS13, resulting in less reactive derivatives. Objective: We hypothesized that HELLP syndrome is characterized by increased amounts of active VWF compared with healthy pregnancy and pre-eclampsia, due to acute activation of endothelial cells. This might contribute to thrombocytopenia and thrombotic microangiopathy. Methods: Active VWF and ADAMTS13 activity were measured in healthy pregnant volunteers (n ¼ 9), patients with pre-eclampsia (n ¼ 6) and patients with HELLP syndrome (n ¼ 14) at similar gestational ages. To study the role of endothelial cell activation, the propeptide/mature VWF ratio was determined, and VWF released by cultured endothelial cells was analyzed. Results: Active VWF levels were increased 2.1-fold in HELLP syndrome compared with healthy pregnant volunteers (P < 0.001) and 1.6-fold compared with patients with pre-eclampsia (P ¼ 0.001). ADAMTS13 activity was moderately decreased in patients with HELLP syndrome compared with healthy pregnant volunteers (P < 0.004), but not compared with patients with pre-eclampsia. The propeptide/mature VWF ratio was increased 1.7-fold compared with healthy pregnant volunteers (P < 0.001) and 1.5-fold compared with patients with pre-eclampsia (P < 0.05). A significant correlation was found between this ratio and the activation factor of VWF (r ¼ 0.68, P < 0.001). The amount of active VWF was increased 1.4-fold in medium of stimulated endothelial cells when compared with non-stimulated cells (P < 0.05). Conclusion: Acute endothelial cell activation in HELLP syndrome and decreased ADAMTS13 activity result in increased amounts of active VWF. This might explain the consumptive thrombocytopenia and thrombotic microangiopathy associated with HELLP syndrome. Inhibition of circulating active VWF could be a potential new approach in the treatment of patients with HELLP syndrome. J Thromb Haemost

We report a case of a pregnant woman with COVID‐19 who developed coagulopathy in the absence of severe clinical symptoms. A polymerase chain reaction test of a vaginal swab was positive for SARS‐CoV‐2 RNA, suggesting a possibility of perinatal transmission. Cesarean delivery was performed because of a non‐reassuring fetal heart rate; the placenta showed increased perivillous fibrin deposition and intervillositis. Moreover, placental infection with SARS‐CoV‐2 was demonstrated by placental immunostaining. The findings suggest a possible relationship between placental fibrin deposition and chronic and acute intervillositis, non‐reassuring fetal heart rate and coagulopathy in pregnant women with COVID‐19. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

OBJECTIVES: To develop a nationwide, evidence-based framework to support prenatal counseling in extreme prematurity, focusing on organization, decision-making, content, and style aspects. METHODS: A nationwide multicenter RAND–modified Delphi method study was performed between November 2016 and December 2017 in the Netherlands. Firstly, recommendations were extracted from literature and previous studies. Secondly, an expert panel (n = 21) with experienced parents, obstetricians, and neonatologists rated the recommendations on importance for inclusion in the framework. Thirdly, ratings were discussed in a consensus meeting. The final set of recommendations was approved and transformed into a framework. RESULTS: A total of 101 recommendations on organization, decision-making, content, and style were included in the framework, including tools to support personalization. The most important recommendations regarding organization were to have both parents involved in the counseling with both the neonatologist and obstetrician. The shared decision-making model was recommended for deciding between active support and comfort care. Main recommendations regarding content of conversation were explanation of treatment options, information on survival, risk of permanent consequences, impossibility to predict an individual course, possibility for multiple future decision moments, and a discussion on parental values and standards. It was considered important to avoid jargon, check understanding, and provide a summary. The expert panel, patient organization, and national professional associations (gynecology and pediatrics) approved the framework. CONCLUSIONS: A nationwide, evidence-based framework for prenatal counseling in extreme prematurity was developed. It contains recommendations and tools for personalization in the domains of organization, decision-making, content, and style of prenatal counseling.

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Corticosteroids are potent antiinflammatory and immunosuppressive drugs, which are used in the treatment of a wide range of medical disorders. During pregnancy, several corticosteroids are administered for maternal as well as fetal reasons. Prednisone and prednisolone show limited transplacental passage and are thus used for treatment of maternal disease. Dexamethasone and betamethasone, drugs that can easily cross the placenta, are more suitable for fetal indications. During the last decade, administration of corticosteroids was introduced in the treatment of hemolysis, elevated liver enzymes, and low platelets (HELLP syndrome), a severe form of preeclampsia unique to human pregnancy. Several randomized, controlled trials as well as other prospective and retrospective studies have been performed to investigate this beneficial effect of corticosteroids on biochemical measures and clinical signs. This review discusses the characteristics of corticosteroids in humans and details the use of corticosteroids during pregnancy. A review of literature on the effect of corticosteroids on HELLP syndrome is given and possible mechanisms of action are discussed.

BACKGROUND: Maternal hyperoxygenation is widely used during labor as an intrauterine resuscitation technique. However, robust evidence regarding its beneficial effect and potential side effects is scarce, and previous studies show conflicting results. OBJECTIVE: To assess the effect of maternal hyperoxygenation upon suspected fetal distress during the second stage of term labor on fetal heart rate, neonatal outcome, maternal side effects, and mode of delivery. MATERIALS AND METHODS: In a single-center randomized controlled trial in a tertiary hospital in The Netherlands, participants were randomized in case of an intermediary or abnormal fetal heart rate pattern during the second stage of term labor, to receive either conventional care or 100% oxygen at 10 L/min until delivery. The primary outcome was the change in fetal heart rate pattern. Prespecified secondary outcomes were Apgar score, umbilical cord blood gas analysis, neonatal intensive care unit admission, perinatal death, free oxygen radical activity, maternal side effects, and mode of delivery. We performed subgroup analyses for intermediary and abnormal fetal heart rate, and for small for gestational age fetuses. RESULTS: From March 2016 through April 2018, a total of 117 women were included. Fetal heart rate patterns could be analyzed in 71 women. Changes in fetal heart rate (defined as improvement, equal, or deterioration) in favor of maternal hyperoxygenation were significant (odds ratio, 5.7; 95% confidence interval, 1.7À19.1) using ordinal logistic regression. Apgar score, umbilical cord blood gas analysis, free oxygen radicals, and mode of delivery showed no significant differences between the intervention and control group. Among women with an abnormal fetal heart rate, there were fewer episiotomies on fetal indication in the intervention group (25%) than in the control group (65%, P < .01). CONCLUSION: Maternal hyperoxygenation has a positive effect on the fetal heart rate in the presence of suspected fetal distress during the second stage of labor. There was no significant difference in the mode of delivery or neonatal outcome; however, significantly fewer episiotomies on fetal indication were performed following maternal hyperoxygenation in the subgroup with abnormal fetal heart rate pattern.

HELLP syndrome is associated with an increased inflammatory response. Circulating IL-6 levels in HELLP syndrome are reduced during prednisolone administration, suggesting a stabilizing effect on the inflammatory endothelial process.