factor xia


Summary: Activated form of factor XI. In the intrinsic pathway, Factor XI is activated to XIa by factor XIIa in the presence of cofactor HMWK; (HIGH MOLECULAR WEIGHT KININOGEN). Factor XIa then activates factor IX to factor IXa in the presence of calcium.

Top Publications

  1. Lin J, Deng H, Jin L, Pandey P, Quinn J, Cantin S, et al. Design, synthesis, and biological evaluation of peptidomimetic inhibitors of factor XIa as novel anticoagulants. J Med Chem. 2006;49:7781-91 pubmed
    Human coagulation factor XIa (FXIa), a serine protease activated by site-specific cleavage of factor XI by thrombin, FXIIa, or autoactivation, is a critical enzyme in the amplification phase of the coagulation cascade...
  2. Navaneetham D, Jin L, Pandey P, Strickler J, Babine R, Abdel Meguid S, et al. Structural and mutational analyses of the molecular interactions between the catalytic domain of factor XIa and the Kunitz protease inhibitor domain of protease nexin 2. J Biol Chem. 2005;280:36165-75 pubmed
    b>Factor XIa (FXIa) is a serine protease important for initiating the intrinsic pathway of blood coagulation...
  3. Peek M, Moran P, Mendoza N, Wickramasinghe D, Kirchhofer D. Unusual proteolytic activation of pro-hepatocyte growth factor by plasma kallikrein and coagulation factor XIa. J Biol Chem. 2002;277:47804-9 pubmed
    ..By screening a panel of serine proteases we identified two new HGF activators, plasma kallikrein and coagulation factor XIa (FXIa)...
  4. Schumacher W, Seiler S, Steinbacher T, Stewart A, Bostwick J, Hartl K, et al. Antithrombotic and hemostatic effects of a small molecule factor XIa inhibitor in rats. Eur J Pharmacol. 2007;570:167-74 pubmed
    The effect of inhibiting activated blood coagulation factor XIa was determined in rat models of thrombosis and hemostasis. BMS-262084 is an irreversible and selective small molecule inhibitor of factor XIa with an IC(50) of 2...
  5. Yang L, Sun M, Gailani D, Rezaie A. Characterization of a heparin-binding site on the catalytic domain of factor XIa: mechanism of heparin acceleration of factor XIa inhibition by the serpins antithrombin and C1-inhibitor. Biochemistry. 2009;48:1517-24 pubmed publisher
    Heparin accelerates inhibition of factor XIa (fXIa) by the serpins antithrombin (AT) and C1-inhibitor (C1-INH) by more than 2 orders of magnitude...
  6. Weis D, Visco D, Faulon J. Data mining PubChem using a support vector machine with the Signature molecular descriptor: classification of factor XIa inhibitors. J Mol Graph Model. 2008;27:466-75 pubmed publisher
    ..In this work, we trained a support vector machine (SVM) classifier using the Signature molecular descriptor on factor XIa inhibitor HTS data...
  7. Geng Y, Verhamme I, Sun M, Bajaj S, Emsley J, Gailani D. Analysis of the factor XI variant Arg184Gly suggests a structural basis for factor IX binding to factor XIa. J Thromb Haemost. 2013;11:1374-84 pubmed publisher
    ..These residues are buried in zymogen FXI, and must be exposed upon conversion to FXIa to permit FIX binding. ..
  8. Gailani D, Ho D, Sun M, Cheng Q, Walsh P. Model for a factor IX activation complex on blood platelets: dimeric conformation of factor XIa is essential. Blood. 2001;97:3117-22 pubmed
  9. Karuturi R, Al Horani R, Mehta S, Gailani D, Desai U. Discovery of allosteric modulators of factor XIa by targeting hydrophobic domains adjacent to its heparin-binding site. J Med Chem. 2013;56:2415-28 pubmed publisher
    ..promising sulfated allosteric modulators (SAMs) of glycosaminoglycan-binding proteins (GBPs), such as human factor XIa (FXIa), we screened a library of 26 synthetic, sulfated quinazolin-4(3H)-ones (QAOs) resulting in the ..

More Information


  1. Schmidt A, Sun M, Ogawa T, Bajaj S, Gailani D. Functional role of residue 193 (chymotrypsin numbering) in serine proteases: influence of side chain length and beta-branching on the catalytic activity of blood coagulation factor XIa. Biochemistry. 2008;47:1326-35 pubmed publisher
    ..To further understand the role of Gly193 in protease activity, we replaced it with Ala or Val in coagulation factor XIa (FXIa)...
  2. Geng Y, Verhamme I, Messer A, Sun M, Smith S, Bajaj S, et al. A sequential mechanism for exosite-mediated factor IX activation by factor XIa. J Biol Chem. 2012;287:38200-9 pubmed publisher
    During blood coagulation, the protease factor XIa (fXIa) activates factor IX (fIX). We describe a new mechanism for this process. FIX is cleaved initially after Arg(145) to form fIX?, and then after Arg(180) to form the protease fIXa?...
  3. Wu W, Sinha D, Shikov S, Yip C, Walz T, Billings P, et al. Factor XI homodimer structure is essential for normal proteolytic activation by factor XIIa, thrombin, and factor XIa. J Biol Chem. 2008;283:18655-64 pubmed publisher
    ..The dimeric structure of FXI is essential for normal proteolytic activation of FXI by FXIIa, thrombin, or FXIa either in solution or on an anionic surface but not for FIX activation by FXIa in solution. ..
  4. Rahgozar S, Yang Q, Giannakopoulos B, Yan X, Miyakis S, Krilis S. Beta2-glycoprotein I binds thrombin via exosite I and exosite II: anti-beta2-glycoprotein I antibodies potentiate the inhibitory effect of beta2-glycoprotein I on thrombin-mediated factor XIa generation. Arthritis Rheum. 2007;56:605-13 pubmed
    ..We also show that anti-beta(2)GPI antibodies potentiate the inhibitory effect of beta(2)GPI on thrombin-mediated factor XIa generation.
  5. Naito K, Fujikawa K. Activation of human blood coagulation factor XI independent of factor XII. Factor XI is activated by thrombin and factor XIa in the presence of negatively charged surfaces. J Biol Chem. 1991;266:7353-8 pubmed
    ..During the activation, factor XI was cleaved at a single Arg-Ile bond by thrombin or factor XIa to produce an amino-terminal 50-kDa heavy chain and a carboxyl-terminal 35-kDa light chain...
  6. Rezaie A, Sun M, Gailani D. Contributions of basic amino acids in the autolysis loop of factor XIa to serpin specificity. Biochemistry. 2006;45:9427-33 pubmed
    ..four basic residues (Arg-144, Lys-145, Arg-147, and Lys-149) in the autolysis loop of the coagulation protease factor XIa (fXIa) for inhibition by serpins...
  7. Lazarova T, Jin L, Rynkiewicz M, Gorga J, Bibbins F, Meyers H, et al. Synthesis and in vitro biological evaluation of aryl boronic acids as potential inhibitors of factor XIa. Bioorg Med Chem Lett. 2006;16:5022-7 pubmed
    A series of functionalized aryl boronic acids were synthesized and evaluated as potential inhibitors of factor XIa. Crystal structures of the protein-inhibitor complexes led to the design and synthesis of second generation compounds ..
  8. Yamashita A, Nishihira K, Kitazawa T, Yoshihashi K, Soeda T, Esaki K, et al. Factor XI contributes to thrombus propagation on injured neointima of the rabbit iliac artery. J Thromb Haemost. 2006;4:1496-501 pubmed
    ..However, the contribution of FXI to thrombus formation on disrupted plaques remains unclear...
  9. Wuillemin W, Bleeker W, Agterberg J, Rigter G, ten Cate H, Hack C. Clearance of human factor XIa-inhibitor complexes in rats. Br J Haematol. 1996;93:950-4 pubmed
    ..AT), alpha 1-antitrypsin (alpha 1AT) and alpha 2-antiplasmin (alpha 2AP) are known inhibitors of coagulation factor XIa (FXIa)...
  10. Geng Y, Verhamme I, Smith S, Sun M, Matafonov A, Cheng Q, et al. The dimeric structure of factor XI and zymogen activation. Blood. 2013;121:3962-9 pubmed publisher
    ..For activation by thrombin, or during autoactivation, the data support a cis-activation mechanism in which the activating protease binds to and activates the same fXI subunit. ..
  11. Navaneetham D, Sinha D, Walsh P. Mechanisms and specificity of factor XIa and trypsin inhibition by protease nexin 2 and basic pancreatic trypsin inhibitor. J Biochem. 2010;148:467-79 pubmed publisher
    b>Factor XIa (FXIa) inhibition by protease nexin-2 (PN2KPI) was compared with trypsin inhibition by basic pancreatic trypsin inhibitor (BPTI). PN2KPI was a potent inhibitor of FXIa (K(i) ? 0.81 nM) and trypsin (K(i) ? 0...
  12. Meijers J, Kanters D, Vlooswijk R, van Erp H, Hessing M, Bouma B. Inactivation of human plasma kallikrein and factor XIa by protein C inhibitor. Biochemistry. 1988;27:4231-7 pubmed
    The inhibition of kallikrein and factor XIa by protein C inhibitor (PCI) was studied. The method of Suzuki et al. [Suzuki, K., Nishioka, J., & Hashimoto, S. (1983) J. Biol. Chem...
  13. Hertzberg M, Facey S, Hogg P. An Arg/Ser substitution in the second epidermal growth factor-like module of factor IX introduces an O-linked carbohydrate and markedly impairs activation by factor XIa and factor VIIa/Tissue factor and catalytic efficiency of factor IXa. Blood. 1999;94:156-63 pubmed
    ..Recombinant factor IXR94S was activated by factor XIa/calcium with an approximately 50-fold reduced rate and by factor VIIa/tissue factor/phospholipid/calcium with an ..
  14. Duga S, Salomon O. Factor XI Deficiency. Semin Thromb Hemost. 2009;35:416-25 pubmed publisher
    ..Survival advantages to patients with severe FXI have been recently reported. Herein, we present new observations related to clinic presentation, genotype-phenotype correlation, and treatment problems in patients with FXI deficiency. ..
  15. Badellino K, Walsh P. Localization of a heparin binding site in the catalytic domain of factor XIa. Biochemistry. 2001;40:7569-80 pubmed
    Inhibition of factor XIa by protease nexin II (K(i) approximately 450 pM) is potentiated by heparin (K(I) approximately 30 pM)...
  16. Deng H, Bannister T, Jin L, Babine R, Quinn J, Nagafuji P, et al. Synthesis, SAR exploration, and X-ray crystal structures of factor XIa inhibitors containing an alpha-ketothiazole arginine. Bioorg Med Chem Lett. 2006;16:3049-54 pubmed
    ..element, a series of small peptidomimetic molecules was designed and synthesized, and their co-crystal structures with factor XIa were studied in an effort to develop smaller, less peptidic inhibitors as antithrombotic agents.
  17. Sinha D, Badellino K, Marcinkiewicz M, Walsh P. Allosteric modification of factor XIa functional activity upon binding to polyanions. Biochemistry. 2004;43:7593-600 pubmed
    ..substrate L-pyroglutamyl-L-prolyl-L-arginyl-p-nitroaniline (S-2366) and on the activation of factor IX by factor XIa have been investigated...
  18. Hanessian S, Larsson A, Fex T, Knecht W, Blomberg N. Design and synthesis of macrocyclic indoles targeting blood coagulation cascade Factor XIa. Bioorg Med Chem Lett. 2010;20:6925-8 pubmed publisher
    The synthesis of a series of novel macrocyclic compounds designed to target blood coagulation Factor XIa is described. The compounds were evaluated for their inhibition of a small set of serine proteases...
  19. Al Horani R, Ponnusamy P, Mehta A, Gailani D, Desai U. Sulfated pentagalloylglucoside is a potent, allosteric, and selective inhibitor of factor XIa. J Med Chem. 2013;56:867-78 pubmed publisher
    Inhibition of factor XIa (FXIa) is a novel paradigm for developing anticoagulants without major bleeding consequences. We present the discovery of sulfated pentagalloylglucoside (6) as a highly selective inhibitor of human FXIa...
  20. Schumacher W, Luettgen J, Quan M, Seiffert D. Inhibition of factor XIa as a new approach to anticoagulation. Arterioscler Thromb Vasc Biol. 2010;30:388-92 pubmed publisher
    ..Together, these data strongly support FXIa inhibition as a viable method to increase the ratio of benefit to risk in an antithrombotic drug. ..
  21. Sinha D, Marcinkiewicz M, Navaneetham D, Walsh P. Macromolecular substrate-binding exosites on both the heavy and light chains of factor XIa mediate the formation of the Michaelis complex required for factor IX-activation. Biochemistry. 2007;46:9830-9 pubmed
    Binding of factor IX (FIX) to an exosite on the heavy chain of factor XIa (FXIa) is essential for the optimal activation of FIX (Sinha, D., Seaman, F. S., and Walsh, P. N. (1987) Biochemistry 26, 3768-3775)...
  22. Zhang J, Tu Y, Lu L, Lasky N, Broze G. Protein Z-dependent protease inhibitor deficiency produces a more severe murine phenotype than protein Z deficiency. Blood. 2008;111:4973-8 pubmed publisher
    ..factor Xa in a calcium ion-, phospholipid-, and PZ-dependent fashion, but also directly inhibits coagulation factor XIa. In murine gene-deletion models, PZ and ZPI deficiency enhances thrombosis following arterial injury and ..
  23. Macquarrie J, Stafford A, Yau J, Leslie B, Vu T, Fredenburgh J, et al. Histidine-rich glycoprotein binds factor XIIa with high affinity and inhibits contact-initiated coagulation. Blood. 2011;117:4134-41 pubmed publisher
    ..These results suggest that, by binding to factor XIIa, HRG modulates the intrinsic pathway of coagulation, particularly in the vicinity of a thrombus where platelet release of HRG and Zn²(+) will promote this interaction. ..
  24. Salameh M, Robinson J, Navaneetham D, Sinha D, Madden B, Walsh P, et al. The amyloid precursor protein/protease nexin 2 Kunitz inhibitor domain is a highly specific substrate of mesotrypsin. J Biol Chem. 2010;285:1939-49 pubmed publisher
    ..show that cleavage of APPI compromises its inhibition of other serine proteases, including cationic trypsin and factor XIa, by 2 orders of magnitude...
  25. Jankowski M, Undas A, Kaczmarek P, Butenas S. Activated factor XI and tissue factor in chronic obstructive pulmonary disease: links with inflammation and thrombin generation. Thromb Res. 2011;127:242-6 pubmed publisher
    ..Previously, circulating active tissue factor (TF) and factor XIa (FXIa) have been reported to be associated with acute coronary syndromes...
  26. Kore A, Shanmugasundaram M. Novel serine protease inhibitors. Pharm Pat Anal. 2012;1:457-68 pubmed publisher
    ..derivatives, arylpropionamides, arylacrylamides, arylpropynamides, arylmethylurea analogs and peptides as factor XIa inhibitors...
  27. Argade M, Mehta A, Sarkar A, Desai U. Allosteric inhibition of human factor XIa: discovery of monosulfated benzofurans as a class of promising inhibitors. J Med Chem. 2014;57:3559-69 pubmed publisher
    b>Factor XIa (fXIa) is being recognized as a prime target for developing safer anticoagulants...
  28. Bertina R, van der Linden I, Mannucci P, Reinalda Poot H, Cupers R, Poort S, et al. Mutations in hemophilia Bm occur at the Arg180-Val activation site or in the catalytic domain of factor IX. J Biol Chem. 1990;265:10876-83 pubmed
    ..Proteolytic cleavage by factor XIa was normal in two Bm variants, but absent at the Arg180-Val bond in the other two...
  29. Miller T, Sinha D, Baird T, Walsh P. A catalytic domain exosite (Cys527-Cys542) in factor XIa mediates binding to a site on activated platelets. Biochemistry. 2007;46:14450-60 pubmed
    The zymogen, factor XI, and the enzyme, factor XIa, interact specifically with functional receptors on the surface of activated platelets...
  30. Chang J, Monroe D, Stafford D, Brinkhous K, Roberts H. Replacing the first epidermal growth factor-like domain of factor IX with that of factor VII enhances activity in vitro and in canine hemophilia B. J Clin Invest. 1997;100:886-92 pubmed
    ..with activated Factor IX, nor was it due to an increased rate of activation by Factor VIIa-tissue factor or by Factor XIa. Rather, the increased activity was due to a higher affinity of Factor IXVIIEGF1 for Factor VIIIa with a Kd for ..
  31. Schmidt A, Ogawa T, Gailani D, Bajaj S. Structural role of Gly(193) in serine proteases: investigations of a G555E (GLY193 in chymotrypsin) mutant of blood coagulation factor XI. J Biol Chem. 2004;279:29485-92 pubmed
    ..Such arguments will apply to other serine proteases with substitutions of Gly(193) with a non-glycine residue. ..
  32. Kitchens C. The contact system. Arch Pathol Lab Med. 2002;126:1382-6 pubmed
    ..Presently, it is not recommended to measure activity of contact factors during routine evaluation of patients who have suffered venous or arterial thromboembolism or acute coronary syndromes. ..
  33. London F, Marcinkiewicz M, Walsh P. A subpopulation of platelets responds to thrombin- or SFLLRN-stimulation with binding sites for factor IXa. J Biol Chem. 2004;279:19854-9 pubmed
    ..These studies refine the results from equilibrium binding studies and suggest that, on average, only a small subpopulation (approximately 10%) of PAR 1-stimulated platelets expose approximately 6000 factor IXa binding sites/platelet. ..
  34. Corte J, Yang W, Fang T, Wang Y, Osuna H, Lai A, et al. Macrocyclic inhibitors of Factor XIa: Discovery of alkyl-substituted macrocyclic amide linkers with improved potency. Bioorg Med Chem Lett. 2017;27:3833-3839 pubmed publisher
    ..Replacement of the chlorophenyltetrazole cinnamide P1 in these optimized macrocycles reduced the polar surface area and improved the oral bioavailability for the series, albeit at the cost of a decrease in potency. ..
  35. Noyes C, Griffith M, Roberts H, Lundblad R. Identification of the molecular defect in factor IX Chapel Hill: substitution of histidine for arginine at position 145. Proc Natl Acad Sci U S A. 1983;80:4200-2 pubmed
    ..amino-terminal from the Arg-Ala peptide bond at 145-146 that is cleaved during the activation of factor IX with factor XIa, was absent in the digest obtained from factor factor IX Chapel Hill...
  36. Konings J, Govers Riemslag J, Spronk H, Waltenberger J, ten Cate H. Activation of the contact system in patients with a first acute myocardial infarction. Thromb Res. 2013;132:138-42 pubmed publisher
    ..The levels of the enzyme inhibitor complexes were not predictive for a recurrent event one year after the first AMI. ..
  37. Puy C, Tucker E, Wong Z, Gailani D, Smith S, Choi S, et al. Factor XII promotes blood coagulation independent of factor XI in the presence of long-chain polyphosphates. J Thromb Haemost. 2013;11:1341-52 pubmed publisher
    ..Inorganic polyphosphates (polyP), which are secreted by activated platelets (short-chain polyP) and accumulate in some bacteria (long-chain polyP), support the contact activation of factor XII (FXII) and accelerate the activation of FXI...
  38. Giannakopoulos B, Gao L, Qi M, Wong J, Yu D, Vlachoyiannopoulos P, et al. Factor XI is a substrate for oxidoreductases: enhanced activation of reduced FXI and its role in antiphospholipid syndrome thrombosis. J Autoimmun. 2012;39:121-9 pubmed publisher
    ..This may have implication for understanding the contribution of FXI to APS thrombosis, and the predisposition to thrombosis in patients with elevated plasma levels of reduced FXI...
  39. Mahdi F, Shariat Madar Z, Schmaier A. The relative priority of prekallikrein and factors XI/XIa assembly on cultured endothelial cells. J Biol Chem. 2003;278:43983-90 pubmed
    ..PK preferential binding to endothelial cells contributes to their anticoagulant nature. ..
  40. Sinha D, Marcinkiewicz M, Lear J, Walsh P. Factor XIa dimer in the activation of factor IX. Biochemistry. 2005;44:10416-22 pubmed
    ..We conclude that, for optimal function in the presence of activated platelets, a preformed dimer of factor XI is not required. ..
  41. Siritapetawee J, Thammasirirak S. Purification and characterization of a heteromultimeric glycoprotein from Artocarpus heterophyllus latex with an inhibitory effect on human blood coagulation. Acta Biochim Pol. 2011;58:521-8 pubmed
    ..The prolonged APTT resulted from the serine protease inhibitor property of HSGPL1, since it reduced activity of human blood coagulation factors XI(a) and ?-XII(a). ..
  42. Tucker E, Verbout N, Leung P, Hurst S, McCarty O, Gailani D, et al. Inhibition of factor XI activation attenuates inflammation and coagulopathy while improving the survival of mouse polymicrobial sepsis. Blood. 2012;119:4762-8 pubmed publisher
    ..Systemic anticoagulation by inhibiting FXI activation or FXIIa procoagulant activity during sepsis may therefore limit the development of disseminated intravascular coagulation without increasing bleeding risks. ..
  43. Sierko E, Zawadzki R, Wojtukiewicz M. [Tissue factor pathway inhibitors]. Pol Merkur Lekarski. 2002;13:66-9 pubmed
    ..TFPI inhibits the activity of factor Xa and the complex of tissue factor and factor VIIa (TF/VIIa). Conversely, TFPI-2 does not inhibits factor Xa, but it is a strong inhibitor of factor XIa, plasma kallikrein, plasmin and trypsin.
  44. Lundblad R, Bergstrom J, De Vreker R, Bray G, Gomperts E, Baker D, et al. Measurement of active coagulation factors in Autoplex-T with colorimetric active site-specific assay technology. Thromb Haemost. 1998;80:811-5 pubmed
    ..8 nM or 11.7 microg/ml; factor VIIa, 68.6 nM or 3.3 microg/ml and factor IIa, 5.3 nM or 0.2 microg/ml. These results are discussed with respect to the mechanism of action of Autoplex-T in the treatment of factor VIII inhibitor patients. ..
  45. Sheehan J, Walke E. Depolymerized holothurian glycosaminoglycan and heparin inhibit the intrinsic tenase complex by a common antithrombin-independent mechanism. Blood. 2006;107:3876-82 pubmed
    ..DHG also accelerated decay of the intact intrinsic tenase complex. Thus, DHG binds to an exosite on factor IXa that overlaps with the binding sites for LMWH and factor VIIIa, disrupting critical factor IXa-factor VIIIa interactions. ..
  46. Park M, Martini W, Dubick M, Salinas J, Butenas S, Kheirabadi B, et al. Thromboelastography as a better indicator of hypercoagulable state after injury than prothrombin time or activated partial thromboplastin time. J Trauma. 2009;67:266-75; discussion 275-6 pubmed publisher
    ..The high incidence of pulmonary embolism indicated that our current prophylaxis regimen could be improved. ..
  47. Christensen K, Larsson R, Emanuelsson H, Elgue G, Larsson A. Effects on blood compatibility in vitro by combining a direct P2Y12 receptor inhibitor and heparin coating of stents. Platelets. 2006;17:318-27 pubmed
    ..The conclusion is that the direct P2Y12 receptor inhibitor AR-C69931MX reduced the different aspects of activation of blood induced by both unmodified and heparin-coated stents. ..
  48. Deguchi H, Fernandez J, Griffin J. Plasma cholesteryl ester transfer protein and blood coagulability. Thromb Haemost. 2007;98:1160-4 pubmed
    ..For clotting initiated by dilute tissue factor or factor XIa, clotting times significantly correlated with CETP antigen levels...
  49. Aktimur A, Gabriel M, Gailani D, Toomey J. The factor IX gamma-carboxyglutamic acid (Gla) domain is involved in interactions between factor IX and factor XIa. J Biol Chem. 2003;278:7981-7 pubmed
    During hemostasis, factor IX is activated to factor IXabeta by factor VIIa and factor XIa. The glutamic acid-rich gamma-carboxyglutamic acid (Gla) domain of factor IX is involved in phospholipid binding and is required for activation by ..
  50. Choi S, Collins J, Smith S, Davis Harrison R, Rienstra C, Morrissey J. Phosphoramidate end labeling of inorganic polyphosphates: facile manipulation of polyphosphate for investigating and modulating its biological activities. Biochemistry. 2010;49:9935-41 pubmed publisher
    ..Our findings open up essentially the entire armamentarium of protein chemistry to modifying polyphosphate, which should greatly facilitate studies of its biological roles. ..
  51. Kondratovich A, Pokhilko A, Ataullakhanov F. Spatiotemporal dynamics of contact activation factors of blood coagulation. Biochim Biophys Acta. 2002;1569:86-104 pubmed
    ..Analysis of the spatiotemporal dynamics of factor XIa and kallikrein in glass-activated human plasma provides evidence that both contact factors remain restricted to ..
  52. Wojcik E, Van den Berg M, Poort S, Bertina R. Modification of the N-terminus of human factor IX by defective propeptide cleavage or acetylation results in a destabilized calcium-induced conformation: effects on phospholipid binding and activation by factor XIa. Biochem J. 1997;323 ( Pt 3):629-36 pubmed
    ..Also the binding of FIX Boxtel to phospholipids and its activation by factor XIa requires a high (>5 mM) calcium concentration...
  53. Canobbio I, Visconte C, Momi S, Guidetti G, Zarà M, Canino J, et al. Platelet amyloid precursor protein is a modulator of venous thromboembolism in mice. Blood. 2017;130:527-536 pubmed publisher
    ..Moreover, the activity of factor XIa (FXIa), but not FXIIa, was higher in APP-KO mice compared with controls...