P-096: Pregnancy-associated thrombotic microangiopathies (Pa-TMA): features of intrarenal blood flow (IBF) in severe preeclampsia (PE), HELLP syndrome and pregnancy-associated atypical hemolytic uremic syndrome (P-aHUS)

2017 ◽  
Vol 151 ◽  
pp. S138
Author(s):  
T. Kirsanova ◽  
M. Vinogradova
Keyword(s):  
Blood Flow ◽  
Hemolytic Uremic Syndrome ◽  
Hellp Syndrome ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Severe Preeclampsia ◽  
Thrombotic Microangiopathies ◽  
Uremic Syndrome ◽  
Intrarenal Blood Flow

scholarly journals Complement Activation and Thrombotic Microangiopathies

2019 ◽  
Vol 14 (12) ◽  
pp. 1719-1732 ◽  
Author(s):  
Marta Palomo ◽  
Miquel Blasco ◽  
Patricia Molina ◽  
Miquel Lozano ◽  
Manuel Praga ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Hemolytic Uremic Syndrome ◽  
Acute Phase ◽  
Complement Activation ◽  
Hellp Syndrome ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Malignant Hypertension ◽  
Clinical Relapse ◽  
Thrombotic Microangiopathies ◽  
Uremic Syndrome

Background and objectivesAtypical hemolytic uremic syndrome is a form of thrombotic microangiopathy caused by dysregulation of the alternative complement pathway. There is evidence showing complement activation in other thrombotic microangiopathies. The aim of this study was to evaluate complement activation in different thrombotic microangiopathies and to monitor treatment response.Design, setting, participants, & measurementsComplement activation was assessed by exposing endothelial cells to sera or activated-patient plasma—citrated plasma mixed with a control sera pool (1:1)—to analyze C5b-9 deposits by immunofluorescence. Patients with atypical hemolytic uremic syndrome (n=34) at different stages of the disease, HELLP syndrome (a pregnancy complication characterized by hemolysis, elevated liver enzymes, and low platelet count) or severe preeclampsia (n=10), and malignant hypertension (n=5) were included.ResultsAcute phase atypical hemolytic uremic syndrome–activated plasma induced an increased C5b-9 deposition on endothelial cells. Standard and lower doses of eculizumab inhibited C5b-9 deposition in all patients with atypical hemolytic uremic syndrome, except in two who showed partial remission and clinical relapse. Significant fibrin formation was observed together with C5b-9 deposition. Results obtained using activated-plasma samples were more marked and reproducible than those obtained with sera. C5b-9 deposition was also increased with samples from patients with HELLP (all cases) and preeclampsia (90%) at disease onset. This increase was sustained in those with HELLP after 40 days, and levels normalized in patients with both HELLP and preeclampsia after 6–9 months. Complement activation in those with malignant hypertension was at control levels.ConclusionsThe proposed methodology identifies complement overactivation in patients with atypical hemolytic uremic syndrome at acute phase and in other diseases such as HELLP syndrome and preeclampsia. Moreover, it is sensitive enough to individually assess the efficiency of the C5 inhibition treatment.

scholarly journals Direct Evidence of Complement Activation in HELLP Syndrome: A Link to Atypical Hemolytic Uremic Syndrome

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1047-1047
Author(s):  
Eleni Gavriilaki ◽  
Arthur Vaught ◽  
Nancy Heuppchen ◽  
Karin Blakemore ◽  
Xuan Yuan ◽  
...  
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Complement Activation ◽  
Hellp Syndrome ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Cell Killing ◽  
Severe Preeclampsia ◽  
Receiver Operating Curve ◽  
Healthy Pregnancy ◽  
Significant Difference ◽  
Uremic Syndrome

Abstract Introduction: HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets) is a severe variant of preeclampsia that leads to severe morbidity and mortality to both the mother and fetus. Delivery is the treatment of choice at or beyond 34 weeks, but there are no good therapies for pregnant women with HELLP before 34 weeks of pregnancy. Although there are no strict criteria for its diagnosis, the Tennessee and Mississippi classifications have been proposed using platelet count (<100,000 or 150,000 cells/microL), lactate dehydrogenase levels (LDH>600 IU/L), bilirubin (>1.2 mg/dL) and aspartate aminotransferase (AST) with or without alanine aminotransferase (ALT) levels (AST >40 or 70 IU/L, ALT>40 IU/L). However, LDH, AST and bilirubin are not specific for liver dysfunction and their elevation may be caused by intravascular hemolysis alone. Recent evidence and clinical similarities suggest a link to atypical hemolytic uremic syndrome (aHUS), a disease of excessive alternative complement pathway (APC) activation. To test this hypothesis we utilized a functional complement assay, the modified Ham test recently described for aHUS diagnosis. Method: Women with classic HELLP, atypical HELLP, preeclampsia with severe features, and women with normal pregnancies were recruited for the study from September 1, 2014 to May 31, 2015. Women with known sickle cell disease, systemic lupus erythematous, antiphospholipid antibody syndrome, or previous diagnosed microangiopathic and hemolytic diseases were excluded. All participants were greater than 23 weeks pregnant. Classic HELLP syndrome was defined as satisfying all Mississippi or Tennessee criteria for HELLP syndrome; while atypical HELLP as having at least one laboratory abnormality in the Mississippi or Tennessee criteria. Sera was collected and sent blinded to the laboratory. APC activation was detected in the modified Ham test and compared to previously described marker of complement activation, serum C5b-9 levels. Furthermore, we tested the in vitro ability of eculizumab to inhibit APC activation. Eculizumab containing serum was collected from a patient with paroxysmal nocturnal hemoglobinuria (PNH) within 60 minutes after the infusion. Results: Serum from 9 women with classic or atypical HELLP, 7 women with severe preeclampsia, and 11 controls (healthy pregnancy) were tested. We found no significant difference in serum C5b-9 levels among patients with HELLP, preeclampsia and controls (p=0.808). However, increased complement activation in the modified Ham test, represented as significantly higher percentage of non-viable cells/cell killing (25.7±19.8% versus 4.1±7.3%, p=0.005), was found in participants with classic or atypical HELLP compared to participants with healthy pregnancy (Figure 1A). Participants with classic HELLP demonstrated significantly more cell killing when compared to severe preeclampsia (38.7+9.8% versus 13.0+11.7, p=0.048). In the ROC (receiver operating curve) analysis, a percentage of killing higher than 20.5% was determined as a cut-off value for the diagnosis of HELLP with 66.7% sensitivity and 88.9% specificity. Importantly, mixing sera from 4 HELLP patients with eculizumab containing serum in different percentages resulted in a significant decrease of cell killing compared to HELLP serum alone (Figure 1B, p=0.007). Conclusions: We have shown that preeclampsia with severe features along with classic and atypical HELLP syndrome may be considered, at least in part, a disease of excessive complement activation. The modified Ham test is a serum-based assay that does not theoretically detect increased complement activation caused by mutations in cell membrane factors. Other pathophysiological mechanisms beyond complement activation may also account for the negative results in 3 HELLP participants. Importantly, the modified Ham test seems a promising tool to identify patients with increased complement activation who may benefit from complement inhibition. If confirmed in a larger cohort, this rapid, inexpensive and highly specific assay may be valuable to select patients for such a clinical trial. Disclosures Brodsky: Alexion Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees.

Treatment of Atypical Hemolytic Uremic Syndrome and Thrombotic Microangiopathies: A Focus on Eculizumab

2013 ◽  
Vol 61 (2) ◽  
pp. 289-299 ◽  
Author(s):  
Jan Schmidtko ◽  
Sven Peine ◽  
Youssef El-Housseini ◽  
Manuel Pascual ◽  
Pascal Meier
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Thrombotic Microangiopathies ◽  
Uremic Syndrome

scholarly journals Hemolysis, Elevated Liver Enzymes, Low Platelets Syndrome Superimposed on Hemolytic Uremic Syndrome

2017 ◽  
Vol 39 (04) ◽  
pp. 195-198 ◽  
Author(s):  
Inês Martins ◽  
Madalena Conceição ◽  
Paulo Gomes ◽  
Nuno Clode
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Hellp Syndrome ◽  
Liver Enzymes ◽  
Future Research ◽  
Thrombotic Microangiopathies ◽  
Laboratory Findings ◽  
Reproductive Immunology ◽  
Elevated Liver Enzymes ◽  
Uremic Syndrome ◽  
Nephrotic Range Proteinuria

AbstractA 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 reproductive immunology. It also reminds clinicians that the overlapping of clinical and laboratory findings in HELLP syndrome makes the diagnosis of other thrombotic microangiopathies during pregnancy a clinical challenge.

scholarly journals Modified Ham test for atypical hemolytic uremic syndrome

Blood ◽  
2015 ◽  
Vol 125 (23) ◽  
pp. 3637-3646 ◽  
Author(s):  
Eleni Gavriilaki ◽  
Xuan Yuan ◽  
Zhaohui Ye ◽  
Alexander J. Ambinder ◽  
Satish P. Shanbhag ◽  
...  
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Cell Lines ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Cell Killing ◽  
Thrombotic Microangiopathies ◽  
Gpi Anchor ◽  
Deficient Cell ◽  
Key Points ◽  
Uremic Syndrome

Key Points GPI-anchor–deficient cell lines are more vulnerable to complement C5b-9 deposition and cell killing from aHUS serum. PIGA-null reagent cell lines can be used to rapidly and reliably distinguish aHUS from other thrombotic microangiopathies.

Membrane cofactor protein mutations in atypical hemolytic uremic syndrome (aHUS), fatal Stx-HUS, C3 glomerulonephritis and the HELLP syndrome

2007 ◽  
Vol 44 (16) ◽  
pp. 3922-3923
Author(s):  
Celia J. Fang ◽  
Veronique Fremeaux-Bacchi ◽  
M. Kathryn Liszewski ◽  
Gaia Pianetti ◽  
Marina Noris ◽  
...  
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Hellp Syndrome ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Membrane Cofactor Protein ◽  
C3 Glomerulonephritis ◽  
Uremic Syndrome ◽  
Protein Mutations
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