ArticleThe Journal of biological chemistry2014
Platelets contain tissue factor pathway inhibitor-2 derived from megakaryocytes and inhibits fibrinolysis.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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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
16 citing papers in PubMed, 27 citations in OpenAlex.
- Activated Platelets Express GPI-Anchored Fibrocystin-L (PKHD1L1), from Granules, Absent or Deficient in Paroxysmal Nocturnal Hemoglobinuria.International journal of molecular sciences · 2026Article
- Circulating extracellular vesicles in plasma carry accessible molecular signatures of aging in mice.bioRxiv : the preprint server for biology · 2026Article
- Venous Thrombogenesis and Cervical Cancer: Plasma MicroRNAs as Prognostic Indicators of Tumor Behavior.International journal of molecular sciences · 2025Article
- Reassessing the Role of Tissue Factor Pathway Inhibitor 2 in Neoplastic and Non-Neoplastic Lesions.Cancers · 2025Review
- Tissue factor pathway inhibitor-2 (TFPI-2)-an underappreciated partaker in cancer and metastasis.Cancer metastasis reviews · 2024Review
- Tissue factor pathway inhibitor 2 as a serum biomarker for endometrial cancer: a single-center retrospective study.BMC cancer · 2024Article
- Tissue Factor Pathway Inhibitors as Potential Targets for Understanding the Pathophysiology of Preeclampsia.Biomedicines · 2023Review
- Structural studies of complexes of kallikrein 4 with wild-type and mutated forms of the Kunitz-type inhibitor BbKI.Acta crystallographica. Section D, Structural biology · 2021Article
- Tissue factor pathway inhibitor‑2 is specifically expressed in ovarian clear cell carcinoma tissues in the nucleus, cytoplasm and extracellular matrix.Oncology reports · 2021Article
- Crystal structures of the complex of a kallikrein inhibitor from Bauhinia bauhinioides with trypsin and modeling of kallikrein complexes.Acta crystallographica. Section D, Structural biology · 2019Article
- Plasma contact factors as therapeutic targets.Blood reviews · 2018Review
- The crystal structure of a multidomain protease inhibitor (HAI-1) reveals the mechanism of its auto-inhibition.The Journal of biological chemistry · 2017Article
- Interaction of factor V B-domain acidic region with its basic region and with TFPI/TFPI2: Structural insights from molecular modeling studies.International biology review · 2017Article
- Article
- Tissue Factor Pathway Inhibitor-2 Gene Polymorphisms Associate With Coronary Atherosclerosis in Chinese Population.Medicine · 2015Observational
- Structure of BbKI, a disulfide-free plasma kallikrein inhibitor.Acta crystallographica. Section F, Structural biology communications · 2015Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Tissue factor pathway inhibitor-2 (TFPI-2) is a homologue of TFPI-1 and contains three Kunitz-type domains and a basic C terminus region. The N-terminal domain of TFPI-2 is the only inhibitory domain, and it inhibits plasma kallikrein, factor XIa, and plasmin. However, plasma TFPI-2 levels are negligible (≤20 pM) in the context of influencing clotting or fibrinolysis. Here, we report that platelets contain significant amounts of TFPI-2 derived from megakaryocytes. We employed RT-PCR, Western blotting, immunohistochemistry, and confocal microscopy to determine that platelets, MEG-01 megakaryoblastic cells, and bone marrow megakaryocytes contain TFPI-2. ELISA data reveal that TFPI-2 binds factor V (FV) and partially B-domain-deleted FV (FV-1033) with K(d) ~9 nM and binds FVa with K(d) ~100 nM. Steady state analysis of surface plasmon resonance data reveal that TFPI-2 and TFPI-1 bind FV-1033 with K(d) ~36-48 nM and bind FVa with K(d) ~252-456 nM. Further, TFPI-1 (but not TFPI-1161) competes with TFPI-2 in binding to FV. These data indicate that the C-terminal basic region of TFPI-2 is similar to that of TFPI-1 and plays a role in binding to the FV B-domain acidic region. Using pull-down assays and Western blots, we show that TFPI-2 is associated with platelet FV/FVa. TFPI-2 (~7 nM) in plasma of women at the onset of labor is also, in part, associated with FV. Importantly, TFPI-2 in platelets and in plasma of pregnant women inhibits FXIa and tissue-type plasminogen activator-induced clot fibrinolysis. In conclusion, TFPI-2 in platelets from normal or pregnant subjects and in plasma from pregnant women binds FV/Va and regulates intrinsic coagulation and fibrinolysis.
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