{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTissue factor pathway inhibitor (TFPI) is the principal endogenous regulator of tissue factor–initiated coagulation. It functions by binding to and inhibiting two essential proteases of the extrinsic pathway: the tissue factor–factor VIIa complex and activated factor X (FXa). Its modular structure—with an acidic N‐terminal region followed by three Kunitz-type domains—confers discrete inhibitory functions: the first Kunitz domain primarily targets the TF–VIIa complex, whereas the second directly inhibits FXa. In addition, TFPI exists both in a soluble form and as a cell surface–associated isoform, ensuring that its rapid inhibition of coagulation occurs in the plasma, on endothelial surfaces, and on activated platelets. This multifaceted molecular architecture underlies TFPI’s central role as a “brake” on coagulation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nTFPI’s inhibitory activity is finely tuned by interactions with various cofactors and by the existence of different isoforms. For instance, TFPIα—expressed in platelets and endothelial cells—employs its basic C-terminal region to interact with other coagulation components such as a short form of factor V, thereby exerting additional control over prothrombinase activity. Moreover, the anticoagulant potency of TFPI is enhanced by protein S, which acts as a cofactor to lower the inhibition constant for FXa. In contrast, the glycosylphosphatidylinositol‐anchored TFPIβ is targeted to cell surfaces where it modulates local TF activity. Together, these isoform‐specific functions and cofactor interactions ensure that TFPI can regulate both the initial burst of thrombin generation and the subsequent propagation phases of coagulation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "13", "end_ref": "24"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its core biochemical interactions, TFPI plays a pivotal clinical role by maintaining vascular hemostasis and by modulating thrombotic risk in diverse pathological states. Alterations in TFPI levels or activity have been implicated in conditions such as diabetes, atherosclerosis, sepsis, and cancer, where dysregulated coagulation contributes to disease progression. In addition, TFPI’s role in mediating the response to inflammatory mediators—and its regulated release from endothelial and placental tissues—points to its broader importance in both local and systemic hemostatic control. These findings, together with observations of circadian variations and interplay with other hemostatic proteins, highlight the clinical potential of TFPI both as a biomarker and as a therapeutic target."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "25", "end_ref": "36"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAdditional regulatory mechanisms further modulate TFPI’s function in hemostasis. Its expression and cell surface localization can be influenced by factors such as heparanase, inflammatory cytokines, and even androgen signaling, while posttranslational modifications and interactions with other proteins (for example, those on endothelial cells or within the bone marrow niche) affect its bioavailability and activity. Such dynamic regulation ensures that TFPI can adapt to both physiologic and pathologic challenges, fine-tuning the balance between coagulation and fibrinolysis in diverse clinical settings including vascular injury, inflammatory disorders, and pregnancy complications."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "37", "end_ref": "46"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Tilman M Hackeng, Kristin M Seré, Guido Tans, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Heparanase induces tissue factor pathway inhibitor expression and extracellular accumulation in endothelial and tumor cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Thromb Haemost (2008)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18217145"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18217145"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "F E Van Den Boogaard, X Brands, M J Schultz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Recombinant human tissue factor pathway inhibitor exerts anticoagulant, anti-inflammatory and antimicrobial effects in murine pneumococcal pneumonia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Thromb Haemost (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1538-7836.2010.04089.x"}], "href": "https://doi.org/10.1111/j.1538-7836.2010.04089.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21029363"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21029363"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "M E Gorczyca, S C Nair, B Jilma, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inhibition of tissue factor pathway inhibitor by the aptamer BAX499 improves clotting of hemophilic blood and plasma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Thromb Haemost (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1538-7836.2012.04790.x"}], "href": "https://doi.org/10.1111/j.1538-7836.2012.04790.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22632032"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22632032"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Michael Dockal, Rudolf Hartmann, Markus Fries, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Small peptides blocking inhibition of factor Xa and tissue factor-factor VIIa by tissue factor pathway inhibitor (TFPI)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M113.533836"}], "href": "https://doi.org/10.1074/jbc.M113.533836"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24275667"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24275667"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Julie A Peterson, Susan A Maroney, Alan E Mast "}, {"type": "b", "children": [{"type": "t", "text": "Targeting TFPI for hemophilia treatment."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Thromb Res (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/S0049-3848(16)30359-0"}], "href": "https://doi.org/10.1016/S0049-3848(16"}, {"type": "t", "text": "30359-0) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27207418"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27207418"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Natalia Reglińska-Matveyev, Helena M Andersson, Suely M Rezende, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "The -33T-->C polymorphism in intron 7 of the TFPI gene influences the risk of venous thromboembolism, independently of the factor V Leiden and prothrombin mutations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Thromb Haemost (2002)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12195688"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12195688"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Paolo Golino, Amelia Ravera, Massimo Ragni, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Involvement of tissue factor pathway inhibitor in the coronary circulation of patients with acute coronary syndromes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Circulation (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/01.CIR.0000105900.21445.3D"}], "href": "https://doi.org/10.1161/01.CIR.0000105900.21445.3D"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14656922"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14656922"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Vijender R Vaidyula, A Koneti Rao, Maria Mozzoli, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Effects of hyperglycemia and hyperinsulinemia on circulating tissue factor procoagulant activity and platelet CD40 ligand."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Diabetes (2006)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16380494"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16380494"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "C Erem, I Nuhoglu, M Yilmaz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Blood coagulation and fibrinolysis in patients with Cushing's syndrome: increased plasminogen activator inhibitor-1, decreased tissue factor pathway inhibitor, and unchanged thrombin-activatable fibrinolysis inhibitor levels."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Endocrinol Invest (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/BF03345709"}], "href": "https://doi.org/10.1007/BF03345709"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19411818"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19411818"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Mirko Pinotti, Cristiano Bertolucci, Francesco Portaluppi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Daily and circadian rhythms of tissue factor pathway inhibitor and factor VII activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arterioscler Thromb Vasc Biol (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/01.ATV.0000153140.13148.e0"}], "href": "https://doi.org/10.1161/01.ATV.0000153140.13148.e0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15604416"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15604416"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Anat Aharon, Benjamin Brenner, Tamar Katz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Tissue factor and tissue factor pathway inhibitor levels in trophoblast cells: implications for placental hemostasis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Thromb Haemost (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1160/TH04-01-0033"}], "href": "https://doi.org/10.1160/TH04-01-0033"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15467908"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15467908"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "H A A M van Vliet, R M Bertina, A E A Dahm, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Different effects of oral contraceptives containing different progestogens on protein S and tissue factor pathway inhibitor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Thromb Haemost (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1538-7836.2008.02863.x"}], "href": "https://doi.org/10.1111/j.1538-7836.2008.02863.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18067603"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18067603"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Cristina Lupu, Hua Zhu, Narcis I Popescu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel protein ADTRP regulates TFPI expression and function in human endothelial cells in normal conditions and in response to androgen."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2011-05-355370"}], "href": "https://doi.org/10.1182/blood-2011-05-355370"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21868574"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21868574"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Matthias Hoke, Paul A Kyrle, Erich Minar, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Tissue factor pathway inhibitor and the risk of recurrent venous thromboembolism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Thromb Haemost (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1160/TH05-06-0412"}], "href": "https://doi.org/10.1160/TH05-06-0412"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16270631"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16270631"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "A Amini-Nekoo, T S Futers, M Moia, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Analysis of the tissue factor pathway inhibitor gene and antigen levels in relation to venous thrombosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Br J Haematol (2001)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1046/j.1365-2141.2001.02752.x"}], "href": "https://doi.org/10.1046/j.1365-2141.2001.02752.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11380428"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11380428"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "I J Welsby, M V Podgoreanu, B Phillips-Bute, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic factors contribute to bleeding after cardiac surgery."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Thromb Haemost (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1538-7836.2005.01337.x"}], "href": "https://doi.org/10.1111/j.1538-7836.2005.01337.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15892865"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15892865"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "Offer Erez, Roberto Romero, Debra Hoppensteadt, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Tissue factor and its natural inhibitor in pre-eclampsia and SGA."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Matern Fetal Neonatal Med (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/14767050802361872"}], "href": "https://doi.org/10.1080/14767050802361872"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19065458"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19065458"}]}, {"type": "r", "ref": 35, "children": [{"type": "t", "text": "Feras Abu Saadeh, Lucy Norris, Sharon O'Toole, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Tumour expresion of tissue factor and tissue factor pathway inhibitor in ovarian cancer- relationship with venous thrombosis risk."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Thromb Res (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.thromres.2013.09.016"}], "href": "https://doi.org/10.1016/j.thromres.2013.09.016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24094893"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24094893"}]}, {"type": "r", "ref": 36, "children": [{"type": "t", "text": "Benedicte Stavik, Grethe Skretting, Hans-Christian Aasheim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Downregulation of TFPI in breast cancer cells induces tyrosine phosphorylation signaling and increases metastatic growth by stimulating cell motility."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Cancer (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1471-2407-11-357"}], "href": "https://doi.org/10.1186/1471-2407-11-357"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21849050"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21849050"}]}, {"type": "r", "ref": 37, "children": [{"type": "t", "text": "Josefin Ahnström, Helena M Andersson, Verity Hockey, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of functionally important residues in TFPI Kunitz domain 3 required for the enhancement of its activity by protein S."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2012-05-432005"}], "href": "https://doi.org/10.1182/blood-2012-05-432005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23074276"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23074276"}]}, {"type": "r", "ref": 38, "children": [{"type": "t", "text": "Alan E Mast, Nayana Acharya, Mark J Malecha, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Characterization of the association of tissue factor pathway inhibitor with human placenta."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arterioscler Thromb Vasc Biol (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/01.atv.0000042456.84190.f0"}], "href": "https://doi.org/10.1161/01.atv.0000042456.84190.f0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12482841"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12482841"}]}, {"type": "r", "ref": 39, "children": [{"type": "t", "text": "Julie A Bastarache, Ling Wang, Zhengming Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Intra-alveolar tissue factor pathway inhibitor is not sufficient to block tissue factor procoagulant activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Lung Cell Mol Physiol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajplung.00372.2007"}], "href": "https://doi.org/10.1152/ajplung.00372.2007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18310227"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18310227"}]}, {"type": "r", "ref": 40, "children": [{"type": "t", "text": "Ewa Sierko, Marek Z Wojtukiewicz, Lech Zimnoch, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression of tissue factor pathway inhibitor (TFPI) in human breast and colon cancer tissue."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Thromb Haemost (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1160/TH09-06-0416"}], "href": "https://doi.org/10.1160/TH09-06-0416"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20062932"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20062932"}]}, {"type": "r", "ref": 41, "children": [{"type": "t", "text": "Neil A Zakai, Pamela L Lutsey, Aaron R Folsom, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Total tissue factor pathway inhibitor and venous thrombosis. The Longitudinal Investigation of Thromboembolism Etiology."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Thromb Haemost (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1160/TH09-10-0693"}], "href": "https://doi.org/10.1160/TH09-10-0693"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20431849"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20431849"}]}, {"type": "r", "ref": 42, "children": [{"type": "t", "text": "YangXin Chen, JingFeng Wang, YouJie Yao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CRP regulates the expression and activity of tissue factor as well as tissue factor pathway inhibitor via NF-kappaB and ERK 1/2 MAPK pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS Lett (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.febslet.2009.07.037"}], "href": "https://doi.org/10.1016/j.febslet.2009.07.037"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19631649"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19631649"}]}, {"type": "r", "ref": 43, "children": [{"type": "t", "text": "Anna C Cunningham, Karen A Hasty, Jan J Enghild, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural and functional characterization of tissue factor pathway inhibitor following degradation by matrix metalloproteinase-8."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BJ20020696"}], "href": "https://doi.org/10.1042/BJ20020696"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12117418"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12117418"}]}, {"type": "r", "ref": 44, "children": [{"type": "t", "text": "Satish Khurana, Lia Margamuljana, Chacko Joseph, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Glypican-3-mediated inhibition of CD26 by TFPI: a novel mechanism in hematopoietic stem cell homing and maintenance."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2012-09-456715"}], "href": "https://doi.org/10.1182/blood-2012-09-456715"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23327927"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23327927"}]}, {"type": "r", "ref": 45, "children": [{"type": "t", "text": "Nina Iversen, Anne Karin Lindahl, Ulrich Abildgaard "}, {"type": "b", "children": [{"type": "t", "text": "Elevated plasma levels of the factor Xa-TFPI complex in cancer patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Thromb Res (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0049-3848(01)00404-2"}], "href": "https://doi.org/10.1016/s0049-3848(01"}, {"type": "t", "text": "00404-2) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11864704"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11864704"}]}, {"type": "r", "ref": 46, "children": [{"type": "t", "text": "Offer Erez, Jimmy Espinoza, Tinnakorn Chaiworapongsa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A link between a hemostatic disorder and preterm PROM: a role for tissue factor and tissue factor pathway inhibitor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Matern Fetal Neonatal Med (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/14767050802361807"}], "href": "https://doi.org/10.1080/14767050802361807"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19012190"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19012190"}]}]}]}