Evidence map›Paper›PMID 25862562›Full record

Trial reportBlood2015

Modified Ham test for atypical hemolytic uremic syndrome.

Eleni Gavriilaki, Xuan Yuan, Zhaohui Ye, Alexander J Ambinder, Satish P Shanbhag, Michael B Streiff, Thomas S Kickler, Alison R Moliterno, C John Sperati, Robert A Brodsky

Open access · bronzeAbstract readClinical Trial
In one paragraph

Trial report in Blood, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
52citing papers in PubMed, 1 pooled it
5.9field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

52 citing papers in PubMed, 1 synthesis or guideline pooled it, 106 citations in OpenAlex.

  1. Interventions for atypical haemolytic uraemic syndrome.The Cochrane database of systematic reviews · 2021
    Pooled it
  2. Trial
  3. Review
  4. Review
  5. Review
  6. Article
  7. Kidney international reports · 2024
    Article
  8. Article
  9. Article
  10. Medical consult: aHUS, TTP? How to distinguish and what to do.Hematology. American Society of Hematology. Education Program · 2023
    Article
  11. Article
  12. Article
  13. Review
  14. Review
  15. Article
  16. A review of the alternative pathway of complement and its relation to HELLP syndrome: is it time to consider HELLP syndrome a disease of the alternative pathway.The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians · 2022
    Review
  17. Review
  18. Frontiers in immunology · 2022
    Review
  19. Review
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 1 institution in 1 country.

Eleni GavriilakiDivision of Hematology, Department of Medicine.ORCID http://orcid.org/0000-0002-8883-8208
Xuan YuanDivision of Hematology, Department of Medicine.
Zhaohui YeDivision of Hematology, Department of Medicine.
Alexander J AmbinderDivision of Hematology, Department of Medicine.
Satish P ShanbhagDivision of Hematology, Department of Medicine.
Michael B StreiffDivision of Hematology, Department of Medicine.
Thomas S KicklerDepartment of Pathology, and.
Alison R MoliternoDivision of Hematology, Department of Medicine.
C John SperatiDivision of Nephrology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.
Robert A BrodskyDivision of Hematology, Department of Medicine.
Johns Hopkins University · US

Funding

TRAINING PROGRAM IN HEMATOLOGYT32HL007525 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI ROBERT A BRODSKY · 1985 to 2026
$6.2M
NHLBI NIH HHS T32 HL007525
6 · The paper itself

Abstract

Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy (TMA) characterized by excessive activation of the alternative pathway of complement (APC). Atypical HUS is frequently a diagnosis of exclusion. Differentiating aHUS from other TMAs, especially thrombotic thrombocytopenic purpura (TTP), is difficult due to overlapping clinical manifestations. We sought to develop a novel assay to distinguish aHUS from other TMAs based on the hypothesis that paroxysmal nocturnal hemoglobinuria cells are more sensitive to APC-activated serum due to deficiency of glycosylphosphatidylinositol- anchored complement regulatory proteins (GPI-AP). Here, we demonstrate that phosphatidylinositol-specific phospholipase C-treated EA.hy926 cells and PIGA-mutant TF-1 cells are more susceptible to serum from aHUS patients than parental EA.hy926 and TF-1 cells. We next studied 31 samples from 25 patients with TMAs, including 9 with aHUS and 12 with TTP. Increased C5b-9 deposition was evident by confocal microscopy and flow cytometry on GPI-AP-deficient cells incubated with aHUS serum compared with heat-inactivated control, TTP, and normal serum. Differences in cell viability were observed in biochemically GPI-AP-deficient cells and were further increased in PIGA-deficient cells. Serum from patients with aHUS resulted in a significant increase of nonviable PIGA-deficient TF-1 cells compared with serum from healthy controls (P < .001) and other TMAs (P < .001). The cell viability assay showed high reproducibility, sensitivity, and specificity in detecting aHUS. In conclusion, we developed a simple, rapid, and serum-based assay that helps to differentiate aHUS from other TMAs.

Indexed as

AdultAgedAtypical Hemolytic Uremic SyndromeCell SurvivalFemaleHumansMaleMembrane ProteinsMiddle AgedPurpura, Thrombotic ThrombocytopenicSerumMembrane Proteinsphosphatidylinositol glycan-class A protein

Identifiers

PMID25862562
PMCPMC4784297
OpenAlexW2094335237

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.