ArticleProceedings of the National Academy of Sciences of the United States of America2012
Absence of hematopoietic tissue factor pathway inhibitor mitigates bleeding in mice with hemophilia.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 75 citations in OpenAlex.
- Inhibition of platelet-surface-bound proteins during coagulation under flow I: TFPI.Biophysical journal · 2023Article
- Regulation of coagulation by tissue factor pathway inhibitor: Implications for hemophilia therapy.Journal of thrombosis and haemostasis : JTH · 2022Review
- Thrombin generation abnormalities in commonly encountered platelet function disorders.International journal of laboratory hematology · 2021Article
- The contribution of TFPIα to the hemostatic response to injury in mice.Journal of thrombosis and haemostasis : JTH · 2021Article
- Intrauterine lethality in Tfpi gene disrupted mice is differentially suppressed during mid- and late-gestation by platelet TFPIα overexpression.Journal of thrombosis and haemostasis : JTH · 2021Article
- Platelet anticoagulant proteins: Modulators of thrombosis propensity within a procoagulant cell.Journal of thrombosis and haemostasis : JTH · 2020Article
- A Molecular Revolution in the Treatment of Hemophilia.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Review
- Anti-tissue factor pathway inhibitor (TFPI) therapy: a novel approach to the treatment of haemophilia.International journal of hematology · 2020Review
- Measurement of plasma and platelet tissue factor pathway inhibitor, factor V and Protein S in people with haemophilia.Haemophilia : the official journal of the World Federation of Hemophilia · 2019Article
- Serum lipoprotein(a) and risk of hemorrhagic stroke among incident peritoneal dialysis patients: a large study from a single center in China.Renal failure · 2019Article
- Defective fibrin deposition and thrombus stability in BambiJournal of thrombosis and haemostasis : JTH · 2019Article
- Tissue factor pathway inhibitor primes monocytes for antiphospholipid antibody-induced thrombosis.Blood · 2019Article
- A systems pharmacokinetic/pharmacodynamic model for concizumab to explore the potential of anti-TFPI recycling antibodies.European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences · 2019Article
- Assessing Blood Clotting and Coagulation Factors in Mice.Current protocols in mouse biology · 2019Article
- Maintaining extraembryonic expression allows generation of mice with severe tissue factor pathway inhibitor deficiency.Blood advances · 2019Article
- Suppressing protein Z-dependent inhibition of factor Xa improves coagulation in hemophilia A.Journal of thrombosis and haemostasis : JTH · 2019Article
- Re-evaluation of mouse tissue factor pathway inhibitor and comparison of mouse and human tissue factor pathway inhibitor physiology.Journal of thrombosis and haemostasis : JTH · 2018Article
- Review
- The Potential Close Future of Hemophilia Treatment - Gene Therapy, TFPI Inhibition, Antithrombin Silencing, and Mimicking Factor VIII with an Engineered Antibody.Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie · 2018Review
- Article
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Authors and funding
9 authors at 5 institutions in 3 countries.
Funding
Abstract
Tissue factor pathway inhibitor (TFPI) blocks thrombin generation via the extrinsic blood coagulation pathway. Because the severe bleeding in patients with hemophilia occurs from deficiency of intrinsic blood coagulation pathway factor VIII or IX, pharmacological agents that inactivate TFPI and, therefore, restore thrombin generation via the extrinsic pathway, are being developed for treatment of hemophilia. Murine models of combined TFPI and factor VIII deficiency were used to examine the impact of TFPI deficiency on bleeding and clotting in hemophilia. In breeding studies, Factor VIII null (F8(-/-)) did not rescue the embryonic death of TFPI null (Tfpi(-/-)) mice. Tfpi(+/-) did not alter the bleeding phenotype of F8(-/-) mice. However, total inhibition of intravascular TFPI through injection of anti-TFPI antibody mitigated tail vein bleeding. Interestingly, tail blood loss progressively decreased at doses greater than needed to totally inhibit plasma TFPI, suggesting that inhibition of a sequestered pool of TFPI released at the injury site mitigates bleeding. Because TFPI is sequestered within platelets and released following their activation, the function of platelet TFPI was examined in F8(-/-) mice lacking hematopoietic cell TFPI that was generated by fetal liver transplantation. Blood loss after tail transection significantly decreased in Tfpi(+/-);F8(-/-) mice with hematopoietic Tfpi(-/-) cells compared with Tfpi(+/-);F8(-/-) mice with Tfpi(+/+) hematopoietic cells. Additionally, following femoral vein injury, Tfpi(+/-);F8(-/-) mice with Tfpi(-/-) hematopoietic cells had increased fibrin deposition compared with identical-genotype mice with Tfpi(+/+) hematopoietic cells. These findings implicate platelet TFPI as a primary physiological regulator of bleeding in hemophilia.
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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.