Evidence map›Paper›PMID 30349890›Full record

ArticleResearch and practice in thrombosis and haemostasis2018

In silico thrombin generation: Plasma composition imbalance and mortality in human immunodeficiency virus.

Kathleen E Brummel-Ziedins, Matthew Gissel, Jacqueline Neuhaus, Álvaro H Borges, David R Chadwick, Sean Emery, James D Neaton, Russell P Tracy, Jason V Baker, INSIGHT SMART, ESPRIT Study Groups

Open access · goldAbstract read
In one paragraph

Article in Research and practice in thrombosis and haemostasis, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
1.8field-weighted citation impact, top 14% 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

5 citing papers in PubMed, 9 citations in OpenAlex.

  1. Dysregulation of Protein S in COVID-19.Best practice & research. Clinical haematology · 2022
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 6 institutions in 4 countries.

Kathleen E Brummel-ZiedinsDepartment of Biochemistry University of Vermont Colchester Vermont USA.
Matthew GisselDepartment of Biochemistry University of Vermont Colchester Vermont USA.
Jacqueline NeuhausDepartment of Biostatistics University of Minnesota Minneapolis Minnesota USA.
Álvaro H BorgesCentre of Excellence for Health, Immunity, and Infections (CHIP) Department of Infectious Diseases, Rigshospitalet University of Copenhagen Copenhagen Denmark.
David R ChadwickJames Cook University Hospital Middlesbrough UK.
Sean EmeryFaculty of Medicine University of Queensland Brisbane Australia.
James D NeatonDepartment of Biostatistics University of Minnesota Minneapolis Minnesota USA.
Russell P TracyDepartment of Biochemistry University of Vermont Colchester Vermont USA.
Jason V BakerDepartment of Medicine University of Minnesota Minneapolis Minnesota USA.
INSIGHT SMART, ESPRIT Study Groups
University of Vermont · USUniversity of Minnesota · USHennepin County Medical Center · USJames Cook University Hospital · GBRigshospitalet · DKUniversity of Queensland · AU

Funding

International Network for Strategic Initiatives in Global HIV Trials (INSIGHT)U01AI068641 · NIAID · UNIVERSITY OF MINNESOTA · PI NEATON, JAMES DENNIS · 2006 to 2010
$120.1M
International Network for Strategic Initiatives in Global HIV Trials (INSIGHT)UM1AI068641 · NIAID · UNIVERSITY OF MINNESOTA · PI NEATON, JAMES DENNIS · 2011 to 2014
$83.5M
COMMUNITY PROGRAMS FOR CLINICAL RESEARCH ON AIDSU01AI046362 · NIAID · SOCIAL AND SCIENTIFIC SYSTEMS, INC. · PI GORDIN, FRED M · 2000 to 2006
$75.9M
International Network for Strategic Initiatives in Global HIV Trials (INSIGHT): STARTUM1AI120197 · NIAID · UNIVERSITY OF MINNESOTA · PI NEATON, JAMES DENNIS · 2015 to 2017
$65.1M
INTERNATIONAL PHASE III IL-2 STUDYU01AI046957 · NIAID · UNIVERSITY OF MINNESOTA TWIN CITIES · PI NEATON, JAMES DENNIS · 1999 to 2005
$56.4M
TERRY BEIRN COMMUNITY PROGRAMS FOR CLINICAL RESEARCH ONU01AI042170 · NIAID · UNIVERSITY OF MINNESOTA TWIN CITIES · PI NEATON, JAMES DENNIS · 1997 to 2006
$23.2M
Targeted anticoagulant therapy to reduce inflammation in treated HIV diseaseR01HL126542 · NHLBI · HENNEPIN HEALTHCARE RESEARCH INSTITUTE · PI BAKER, JASON V, KEY, NIGEL S. · 2014 to 2017
$2.3M
NHLBI NIH HHS R01 HL126542NIAID NIH HHS U01 AI042170NIAID NIH HHS U01 AI046362NIAID NIH HHS U01 AI046957NIAID NIH HHS U01 AI068641NIAID NIH HHS UM1 AI068641
6 · The paper itself

Abstract

backgroundEffective HIV treatment with antiretroviral therapy has prolonged survival and shifted causes of death to non-AIDS illnesses such as cardiovascular disease. We have shown that inflammation and HIV viral load associate with pro- and anticoagulant factor imbalances resulting in increased thrombin generation when mathematically modeled. We explore the hypothesis that factor compositional imbalance, corresponding to increased in silico thrombin generation, predicts mortality among HIV+ persons.

methodsIn a nested case-control study of HIV+ individuals on continuous antiretroviral therapy in two large trials, we evaluated cases (any non-violent mortality, n = 114) and matched controls (n = 318). Thrombin generation in response to a tissue-factor initiator for each individual was calculated by a mathematical model incorporating levels of factors (F)II, V, VII, VIII, IX, X, antithrombin, tissue factor pathway inhibitor, and protein C (PC) measured at study entry to the trials. In silico thrombin generation metrics included clot time, maximum rate (MaxR), maximum level (MaxL), and area under the curve (AUC).

resultsLevels of antithrombin and PC decreased, while FV and FVIII were higher in cases vs controls. This resulted in a more procoagulant phenotype with increased MaxR, MaxL, and AUC in cases compared to controls (

conclusionsAntithrombin, FV, FVIII, and PC were the major contributors to the increased thrombin generation associated with mortality risk. Our results suggest that mortality in HIV is associated with an increase in in silico thrombin generation via altered balance of pro- and anticoagulant factors, likely due to an inflammatory response signal, and resulting coagulopathy.

Indexed as

blood coagulation factorsHIVinflammationin silicomathematical modelmortalitythrombin generation

Identifiers

PMID30349890
PMCPMC6178732
OpenAlexW2892373230

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.