Placental sFLT1 is associated with complement activation and syncytiotrophoblast damage in preeclampsia.

Placental sFLT1 is associated with complement activation and syncytiotrophoblast damage in preeclampsia. Hypertens Pregnancy. 2019 Jul 10;:1-7 Authors: Yonekura Collier AR, Zsengeller Z, Pernicone E, Salahuddin S, Khankin EV, Karumanchi SA Abstract The immune complement system protects against pathogens; however, excess activation results in disease like hemolytic uremic syndrome, a clinical imitator of preeclampsia. Vascular endothelial factor (VEGF) protects against aberrant complement activation and is inhibited by soluble fms-like tyrosine kinase-1 (sFLT1) in other organs. We hypothesize that sFLT1 promotes complement-mediated placental damage through VEGF inhibition in preeclampsia. Objective: Quantify placental complement activity and sFLT1 expression in preeclampsia, and the subgroup of preeclampsia with hemolysis elevated liver enzymes low platelets (HELLP) syndrome. Methods: Placental complement activation marker C4d, membrane attack complex (MAC), and sFLT1 expression was quantified using immunofluores cence microscopy. Results: Placentas from 18 controls, 25 preeclampsia, including 6 cases of HELLP syndrome were identified. Placental C4d expression was greater in PE (median 6.4 [IQR: 5.1, 8.3]) compared to controls (4.4 [3.6, 5.5]; p = 0.003). MAC expression was also increased in preeclampsia compared to controls (6.5 [5.8, 8.7]; 5.4 [2.9, 5.9], p = 0.001). Placental sFLT1 expression was also higher in preeclampsia (p
Source: Hypertension in Pregnancy - Category: OBGYN Tags: Hypertens Pregnancy Source Type: research

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Complement-mediated thrombotic microangiopathy (TMA), also known as atypical hemolytic uremic syndrome (aHUS) is a rare, hereditary, progressive, life-threatening disorder caused by a disruption in regulation of the alternative pathway of the complement system. Eculizumab, a terminal complement inhibitor, has emerged as a first-line therapy, however data are limited to small case series (Brocklebank et al., 2017). Here, we present a diagnostically challenging case of complement-mediated TMA, who received eculizumab therapy with excellent hematologic response.A 68-year-old female with history of possible Sjogren's syndrome,...
Source: Blood - Category: Hematology Authors: Tags: 311. Disorders of Platelet Number or Function Source Type: research
Publication date: April 2018Source: Pregnancy Hypertension, Volume 12Author(s): M. Gupta, B.B. Feinberg, R.M. BurwickAbstractThrombotic microangiopathy (TMA) disorders are characterized by microangiopathic hemolytic anemia, thrombocytopenia and end-organ injury. In pregnancy and postpartum, TMA is most commonly encountered with HELLP (hemolysis, elevated liver enzymes, low platelet count syndrome) or preeclampsia with severe features, but rarely TMA is due to thrombotic thrombocytopenic purpura (TTP) or atypical hemolytic uremic syndrome (aHUS). Due to overlapping clinical and laboratory features, TTP and aHUS are often mi...
Source: Pregnancy Hypertension: An International Journal of Womens Cardiovascular Health - Category: OBGYN Source Type: research
Publication date: Available online 16 February 2018 Source:Pregnancy Hypertension Author(s): M. Gupta, B.B. Feinberg, R.M. Burwick Thrombotic microangiopathy (TMA) disorders are characterized by microangiopathic hemolytic anemia, thrombocytopenia and end-organ injury. In pregnancy and postpartum, TMA is most commonly encountered with HELLP (hemolysis, elevated liver enzymes, low platelet count syndrome) or preeclampsia with severe features, but rarely TMA is due to thrombotic thrombocytopenic purpura (TTP) or atypical hemolytic uremic syndrome (aHUS). Due to overlapping clinical and laboratory features, TTP and aHUS are o...
Source: Pregnancy Hypertension: An International Journal of Womens Cardiovascular Health - Category: OBGYN Source Type: research
We present one case of HUS caused by adenovirus in a boy of 1 year and 7 months old with severe evolution, which required peritoneal dialysis.Diagnose:Stool sample repeated examination for adenovirus antigen was positive in 2 samples.Intervention:During hospitalization, the patient required 8 peritoneal dialysis sessions.Outcome:The renal function was corrected on discharge, the patient required cardiovascular monitoring 1 month after discharge.Lesson:Although the most common cause that leads to HUS remains STEC, other etiologies like viral ones that may be responsible for severe enteric infection with progression into HUS...
Source: Medicine - Category: Internal Medicine Tags: Research Article: Clinical Case Report Source Type: research
ABSTRACT Thrombotic microangiopathy (TMA) arises in a variety of clinical circumstances with the potential to cause significant dysfunction of the kidneys, brain, gastrointestinal tract and heart. TMA should be considered in all patients with thrombocytopenia and anaemia, with an immediate request to the haematology laboratory to look for red cell fragments on a blood film. Whilst TMA of any aetiology generally demands prompt treatment, this is especially so in thrombotic thrombocytopenic purpura (TTP) and atypical haemolytic uraemic syndrome (aHUS), where organ failure may be precipitous, irreversible and fatal. In all ad...
Source: Nephrology - Category: Urology & Nephrology Authors: Tags: Review Article Source Type: research
Conclusion It is widely acknowledged the postpartum angiopathy may represent a hormonally mediated effect on the brain vessel intima precipitated by acute hypertension, evidently with affection of different territories (Cases 2, 3). Despite of different territorial manifestations the vascular events in this study did demonstrate similar features with an acute self-limited course and clinical symptomatology depending on the location. Various hormonal and biochemical factors have been identified playing a role in the deregulation of cerebral vascular tone of both the postpartum period and the RCVS. Some of them are common fo...
Source: Journal of NeuroInterventional Surgery - Category: Neurosurgery Authors: Tags: Electronic Poster Abstracts Source Type: research
Abstract A pregnancy complicated by typical hemolytic uremic syndrome (HUS) and hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome is reported. At 20 weeks of gestation, a case of HUS was diagnosed, with Shiga toxin-producing Escherichia coli identified. Plasmapheresis allowed continuation of the pregnancy for 5 weeks. Superimposed preeclampsia and HELLP syndrome were diagnosed after the establishment of nephrotic range proteinuria, hypertension and recurrence of hemolysis. This is a singular case, as it demonstrates that HELLP syndrome can superimpose upon HUS, a fact that can impact future research on repr...
Source: Revista Brasileira de Ginecologia e Obstetricia - Category: OBGYN Source Type: research
ConclusionEarly recognition of atypical hemolytic uremic syndrome is often difficult as several other conditions also manifest as thrombotic microangiopathy during pregnancy, causing delay in initiating appropriate treatment. Our case suggests that treatment of atypical hemolytic uremic syndrome in early trimester of pregnancy with eculizumab results in good outcome to mother and fetus.
Source: Experimental Hematology and Oncology - Category: Cancer & Oncology Source Type: research
Pregnancy-associated thrombotic microangiopathy is a very rare condition; however, it significantly increases fetal or maternal morbidity and mortality. Pregnancy may trigger atypical hemolytic uremic syndrome (aHUS) or thrombotic thrombocytopenic purpura. The risk for pregnancy-associated aHUS is highest during the second pregnancy. The outcome is usually poor with 50 –60% mortality; renal dysfunction and hypertension are the rule in those who survive the acute episode. After the development of complement regulation mechanisms and aHUS pathogenesis, eculizumab has been widely used as a first-line treatment in aHUS. ...
Source: Case Reports in Nephrology and Dialysis - Category: Urology & Nephrology Source Type: research
CONCLUSION: This case illustrates the importance of distinguishing atypical hemolytic uremic syndrome from preeclampsia. PMID: 27054930 [PubMed - as supplied by publisher]
Source: Obstetrics and Gynecology - Category: OBGYN Authors: Tags: Obstet Gynecol Source Type: research
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