Seeking the mechanism(s) of action for corticosteroids in HELLP syndrome: SMASH study

Wallace, Kedra; Martin, James N.; Tam, Kiran Tam; Wallukat, Gerd; Dechend, Ralf; LaMarca, Babbette; Owens, Michelle

doi:10.1016/j.ajog.2013.01.049

Cited by 35 publications

(37 citation statements)

References 42 publications

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“…Therefore, it is possible that in our study the smaller steroid doses used for induction of lung maturity do not exercise an effect discernible through the circulatory levels of the investigated angiogenic factors. Inclusion in the data analysis of angiogenic factor levels from postpartum samples could have also significantly confounded the sFlt-1 and sEng results published by Wallace et al 35 In humans, prednisolone lowers the level of maternal IL-6, but not IL-1β, IL-10, and soluble IL-6R in HELLP syndrome. 36 The results of this study, consistent with a temporary decrease in the maternal serum levels of the same cytokine, are provocative because IL-6 engages the IL-6 receptor, which is restricted to a few immune cell types such as neutrophils and leukocytes.…”

Section: Discussionmentioning

confidence: 96%

“…34 Therefore, we do not dismiss the prospect of a steroid dose-dependent effect on angiogenesis. Wallace et al 35 showed that, in patients with HELLP syndrome, dexamethasone was associated with improved clinical signs, laboratory values, and a decrease in circulating levels of IL-6, sFlt-1, and sEng. The Mississippi steroid protocol used high doses of dexamethasone and focused on the first 24 hours after steroid administration.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Antenatal Corticosteroids Impact the Inflammatory Rather Than the Antiangiogenic Profile of Women With Preeclampsia

et al. 2014

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Circulating antiangiogenic factors and proinflammatory cytokines are implicated in the pathogenesis of preeclampsia. This study was performed to test the hypothesis that steroids modify the balance of inflammatory and proangiogenic and antiangiogenic factors that potentially contribute to the patient’s evolving clinical state. Seventy singleton women, admitted for antenatal corticosteroid treatment, were enrolled prospectively. The study group consisted of 45 hypertensive women: chronic hypertension (n=6), severe preeclampsia (n=32), and superimposed preeclampsia (n=7). Normotensive women with shortened cervix (<2.5 cm) served as controls (n=25). Maternal blood samples of preeclampsia cases were obtained before steroids and then serially up until delivery. A clinical severity score was designed to clinically monitor disease progression. Serum levels of angiogenic factors (soluble fms-like tyrosine kinase-1 [sFlt-1], placental growth factor [PlGF], soluble endoglin [sEng]), endothelin-1 (ET-1), and proinflammatory markers (IL-6, C-reactive protein [CRP]) were assessed before and after steroids. Soluble IL-2 receptor (sIL-2R) and total immunoglobulins (IgG) were measured as markers of T- and B-cell activation, respectively. Steroid treatment coincided with a transient improvement in clinical manifestations of preeclampsia. A significant decrease in IL-6 and CRP was observed although levels of sIL-2R and IgG remained unchanged. Antenatal corticosteroids did not influence the levels of angiogenic factors but ET-1 levels registered a short-lived increase poststeroids. Although a reduction in specific inflammatory mediators in response to antenatal steroids may account for the transient improvement in clinical signs of preeclampsia, inflammation is unlikely to be the major contributor to severe preeclampsia or useful for therapeutic targeting.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Antenatal Corticosteroids Impact the Inflammatory Rather Than the Antiangiogenic Profile of Women With Preeclampsia

et al. 2014

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“…There are several conditions in differential diagnosis with HELLP: pregnancy-related diseases (benign thrombocytopenia and acute fatty liver of pregnancy); infectious, inflammatory diseases not specifically related to pregnancy (virus hepatitis, cholangitis, cholecystitis); diseases characterized by thrombocytopenia (immunologic thrombocytopenia, folate deficiency, systemic lupus erythematosus, APS); and diseases that may mimic HELLP (thrombotic thrombocytopenic purpura and hemolytic uremic syndrome). The efficacy of corticosteroids (which can reduce inflammation and improve maternal platelet count) in the HELLP syndrome confirms the role of the inflammatory and angiogenic imbalance as well as of immune-abnormalities in the pathophysiology of the HELLP syndrome [47,48]. Moreover, the strategy of treatment in APS and HELLP patients is similar and still a matter of debate: aspirin, low molecular weight heparin, plasma exchange, fresh frozen plasma administration, and intravenous immunoglobulins have been considered in the management of HELLP treatment.…”

Section: Diagnosis and Therapeutic Optionsmentioning

confidence: 94%

HELLP syndrome: a complication or a new autoimmune syndrome?

Triggianese¹,

Perricone²,

Perricone³

et al. 2014

Reumatologia

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Słowa kluczowe: zespół HELLP, powikłania ciąży, możliwości terapeutyczne. S t r e s z c z e n i eZespół HELLP (hemolysis, elevated liver enzymes, low platelets) jest schorzeniem występującym u kobiet w ciąży. Składają się na niego następujące objawy: hemoliza ze zwiększonym stężeniem dehydrogenazy mleczanowej, zwiększonym stężeniem enzymów wątro-bowych oraz obniżona liczba płytek krwi. Zespół HELLP uznawany jest za ciężką postać zaburzeń nadciśnieniowych wywołanych cią-żą, do których należą także stan przedrzucawkowy oraz rzucawka. Objawy zaburzeń zaczynają pojawiać się od 20. tygodnia ciąży. Wszystkie te choroby mają charakter wieloukładowy, specyficzny dla ciąży i wiążą się ze wzrostem ciśnienia krwi oraz podwyższo-ną chorobowością/śmiertelnością noworodków i matek. Badania obserwacyjne wskazują, że leczenie zespołu HELLP lekami steroidowymi może przynieść poprawę parametrów hematologicznych i biochemicznych u matek, a także poprawę rokowania u noworodków. Celem niniejszej pracy jest wykazanie, że zespół HELLP można uznać za niezależne schorzenie autoimmunologiczne. Biomarkery immunologiczne mogą być użytecznym narzędziem usprawniają-cym diagnostykę i leczenie kobiet z zespołem HELLP dzięki określe-niu etiologii leżącej u podłoża tego zespołu. Address for correspondence:Prof. Caterina De Carolis, MD, Gynaecology and Obstetrics II, Azienda Ospedaliera San Giovanni-Addolorata, Via dell' Amba Aradam 9, 00184 Rome, Italy, phone: +39-0677055657, e-mail: c.decarolis@fastwebnet.it Submitted: 3.10.2014 S u m m a r yThe HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome is a pregnancy-specific disease characterized by hemolysis with elevated lactate dehydrogenase, elevated liver enzymes, and decreased platelet count. It is considered a severe variant of the hypertensive disorders that occur during pregnancy together with the pre-eclampsia (PE) and the eclampsia giving symptoms in the mother from 20 weeks' gestation onward. All these conditions are multi-system pregnancy-related diseases associated with an increase in blood pressure and in both the perinatal and the maternal morbidity/mortality. Observational studies suggest that steroid treatment in HELLP syndrome may improve the hematological and biochemical features in the mother and the perinatal outcome. The present review aims to show that the HELLP syndrome may be considered as an autoimmune disorder itself. Biomarkers of the immune system can be a useful tool improving the diagnostic and therapeutic management of women with HELLP by delineating the underlying etiology of this syndrome.

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“…In patients with severe preeclampsia and HELLP syndrome, the platelet count can be increased to 50,000/µL or above by two means separately or in combination: platelet pack transfusion and potent glucocorticoid administration. Antenatal corticosteroid administration has been reported to increase the platelet count; its use has been debated recently (30)(31)(32). It has also been shown to increase the utilization of neuraxial anesthesia among parturients (33).…”

Section: Discussionmentioning

confidence: 99%