Arie Franx

Acute activation of the endothelium results in increased levels of active von Willebrand factor in hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome

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 = 9), patients with pre‐eclampsia (n = 6) and patients with HELLP syndrome (n = 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 = 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 = 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.

Corticosteroids, pregnancy, and HELLP syndrome: a review.

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. Target Audience: Obstetricians & Gynecologists, Family Physicians Learning Objectives: After completion of this article, the reader should be able to compare the relative strength of the commercially available steroids, to outline the pharmacologic characteristics of glucocorticoids in humans, to compare the anti-inflammatory characteristics of corticosteroids, to explain the changes in glucocorticoid metabolism during pregnancy, and to list the effects of corticosteroids on the fetus.

Proactive Support of Labor: Personal continuity and continuous support

Giving birth is a parasympathetic process, a physiological condition that requires a feeling of ease, rest, comfort, confidence, and security. When these environmental conditions are not met, anxiety and fear inevitably trigger a stress response that inhibits uterine contractions and increases the likelihood of prolonged, dysfunctional labor (Chapter 7). Parasympathetic dominance in labor is best promoted by a one-on-one female companion and the personal attention of a trustworthy professional who watches over the parturient’s safety and ensures that labor progresses. This is a double-edged sword: the demanding requirements of non-stop presence, personal commitment, and continuous labor support are strongly correlated with a fixed limit on the maximum duration of labor, because neither is possible without the other. Work schedules exceeding 12 hours are unrealistic.