ArticleBlood2009
Genetic elimination of prothrombin in adult mice is not compatible with survival and results in spontaneous hemorrhagic events in both heart and brain.
Article in Blood, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
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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.
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.
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Who cites it
33 citing papers in PubMed, 60 citations in OpenAlex.
- Novel Function for Endothelial Protease-Activated Receptors in Modulating Insulin Receptor Activity With Implications for Diabetes.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Effects of Prothrombin on Podocytopathy and Proteinuria in Glomerular Disease.Journal of the American Society of Nephrology : JASN · 2025Article
- Prothrombin prevents fatal T cell-dependent anemia during chronic virus infection of mice.JCI insight · 2025Article
- Novel strategies in antithrombotic therapy: targeting thrombosis while preserving hemostasis.Frontiers in cardiovascular medicine · 2023Review
- Genetic duplication of tissue factor reveals subfunctionalization in venous and arterial hemostasis.PLoS genetics · 2022Article
- Fishing for answers to hemostatic and thrombotic disease: Genome editing in zebrafish.Research and practice in thrombosis and haemostasis · 2022Review
- Diagnostic circulating biomarkers to detect vision-threatening diabetic retinopathy: Potential screening tool of the future?Acta ophthalmologica · 2022Review
- Fibrin(ogen) engagement of S. aureus promotes the host antimicrobial response and suppression of microbe dissemination following peritoneal infection.PLoS pathogens · 2022Article
- Host fibrinogen drives antimicrobial function inProceedings of the National Academy of Sciences of the United States of America · 2021Article
- Disruption of the kringle 1 domain of prothrombin leads to late onset mortality in zebrafish.Scientific reports · 2020Article
- Role of the coagulation system in the pathogenesis of sickle cell disease.Blood advances · 2019Article
- Thrombin Signaling Promotes Pancreatic Adenocarcinoma through PAR-1-Dependent Immune Evasion.Cancer research · 2019Article
- Molecular Mechanisms and Determinants of Innovative Correction Approaches in Coagulation Factor Deficiencies.International journal of molecular sciences · 2019Review
- Glial cells maintain synapses by inhibiting an activity-dependent retrograde protease signal.PLoS genetics · 2019Article
- Absence of functional compensation between coagulation factor VIII and plasminogen in double-knockout mice.Blood advances · 2018Article
- A combined deficiency of tissue factor and PAR-4 is associated with fatal pulmonary hemorrhage in mice.Thrombosis research · 2016Article
- Article
- Protective and detrimental effects of neuroectodermal cell-derived tissue factor in mouse models of stroke.JCI insight · 2016Article
- Fibrinogen Is at the Interface of Host Defense and Pathogen Virulence in Staphylococcus aureus Infection.Seminars in thrombosis and hemostasis · 2016Review
- Article
Corrections and comments
- Commented on byBleeding hearts.2009
Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
Mice carrying a conditional prothrombin knockout allele (fII(lox)) were established to develop an experimental setting for exploring the importance of thrombin in the maintenance of vascular integrity, the inflammatory response, and disease processes in adult animals. In the absence of Cre-mediated recombination, homozygous fII(lox/lox) mice or compound heterozygous mice carrying one fII(lox) allele and one constitutive-null allele were viable. Young adults exhibited neither spontaneous bleeding events nor diminished reproductive success. However, the induction of Cre recombinase in fII(lox) mice using the poly I:C-inducible Mx1-Cre system resulted in the rapid and near-complete recombination of the fII(lox) allele within the liver, the loss of circulating prothrombin, and profound derangements in coagulation function. Consistent with the notion that thrombin regulates coagulation and inflammatory pathways, an additional early consequence of reducing prothrombin was impaired antimicrobial function in mice challenged with Staphylococcus aureus peritonitis. However, life expectancy in unchallenged adults genetically depleted of prothrombin was very short ( approximately 5-7 days). The loss of viability was associated with the development of severe hemorrhagic events within multiple tissues, particularly in the heart and brain. Unlike the constitutive loss of either clotting or platelet function alone, the conditional loss of prothrombin is uniformly not compatible with maintenance of hemostasis or long-term survival.
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Registered trials
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.