https://doi.org/10.4081/btvb.2022.11
The Von Willebrand factor-ADAMTS-13 axis: a two-faced Janus in bleeding and thrombosis
Submitted: 17 January 2022
Accepted: 1 April 2022
Published: 26 April 2022
Accepted: 1 April 2022
Abstract Views: 1860
PDF: 310
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Authors
Von Willebrand factor (VWF), a blood multimeric protein with a very high molecular weight, plays a crucial role in the primary hemostasis, the physiological process characterized by the adhesion of blood platelets to the injured vessel wall. Hydrodynamic forces are responsible for the VWF multimers conformational transitions from a globular to a stretched linear conformation. These characteristics render this protein a valuable object to be investigated by mechanochemistry, the biophysical chemistry branch that studies the effects of shear forces on protein conformation. This review will focus on the structural elements of the VWF molecule involved in the biochemical response to shear forces. The stretched VWF conformation favors the interaction with the platelet GpIb and at the same time with ADAMTS-13, the zinc-protease that cleaves VWF in the A2 domain, limiting its prothrombotic capacity. It is important to consider the level or the function of VWF or ADAMTS-13 always in relation each other, keeping in mind that in many thrombotic forms of microangiopathies the reduction of the ratio between the ADAMTS-13 activity and the VWF level (lower than 0.5) can be a valuable parameter to predict a real thrombotic risk. Hence, a significant increase in VWF level alone, even without any reduction of ADAMTS-13 concentration, would still be responsible for a significant reduction of the ADAMTS-13/VWF ratio, which ultimately could reflect or predict a prothrombotic risk. Future studies will have to validate the concept whether ADAMTS-13/VWF ratio could a valuable and reliable biomarker to predict or confirm the presence of thrombotic risk in several morbid conditions.
Sadler JE. Biochemistry and genetics of von Willebrand factor. Annu Rev Biochem.1998;67:395-424.
DOI: https://doi.org/10.1146/annurev.biochem.67.1.395
Ruggeri ZM, Mendolicchio GL. Adhesion mechanisms in platelet function. Circ Res 2007;100:1673-85.
DOI: https://doi.org/10.1161/01.RES.0000267878.97021.ab
Lenting PJ, Casari C, Christophe OD, Denis CV. von Willebrand factor: the old, the new and the unknown. J Thromb Haemost 2012;10:2428-37.
DOI: https://doi.org/10.1111/jth.12008
Huck V, Schneider MF, Gorzelanny C, Schneider SW. The various states of von Willebrand factor and their function in physiology and pathophysiology. Thromb Haemost 2014;111:598-609.
DOI: https://doi.org/10.1160/TH13-09-0800
Schneider SW, Nuschele S, Wixforth A, et al. Shear-induced unfolding triggers adhesion of von Willebrand factor fibers. Proc Natl Acad Sci U S A 2007;104:7899-903.
DOI: https://doi.org/10.1073/pnas.0608422104
Zhang Q, Zhou YF, Zhang CZ, et al. Structural specializations of A2, a force-sensing domain in the ultralarge vascular protein von Willebrand factor. Proc Natl Acad Sci U S A 2009;106:9226-31.
DOI: https://doi.org/10.1073/pnas.0903679106
Zhang X, Halvorsen K, Zhang CZ, et al. Mechanoenzymatic cleavage of the ultralarge vascular protein von Willebrand factor. Science 2009;324:1330-4.
DOI: https://doi.org/10.1126/science.1170905
Mancuso DJ, Tuley EA, Westfield LA, et al. Structure of the gene for human von Willebrand factor. J Biol Chem 1989;264:19514-27.
DOI: https://doi.org/10.1016/S0021-9258(19)47144-5
Titani K, Kumar S, Takio K, et al. Amino acid sequence of human von Willebrand factor. Biochemistry. 1986;25:3171-84.
DOI: https://doi.org/10.1021/bi00359a015
Savage B, Saldivar E, Ruggeri ZM. Initiation of platelet adhesion by arrest onto fibrinogen or translocation on von Willebrand factor. Cell 1996;84:289-97.
DOI: https://doi.org/10.1016/S0092-8674(00)80983-6
Ruggeri ZM, Orje JN, Habermann R, et al. Activation-independent platelet adhesion and aggregation under elevated shear stress. Blood 2006;108:1903-10.
DOI: https://doi.org/10.1182/blood-2006-04-011551
Nurden AT. Clinical significance of altered collagen-receptor functioning in platelets with emphasis on glycoprotein VI. Blood Rev 2019:100592.
DOI: https://doi.org/10.1016/j.blre.2019.100592
Nissinen L, Koivunen J, Kapyla J, et al. Novel alpha2beta1 integrin inhibitors reveal that integrin binding to collagen under shear stress conditions does not require receptor preactivation. J Biol Chem 2012;287:44694-702.
DOI: https://doi.org/10.1074/jbc.M111.309450
Cruz MA, Yuan H, Lee JR, et al. Interaction of the von Willebrand factor (vWF) with collagen. Localization of the primary collagen-binding site by analysis of recombinant vWF a domain polypeptides. J Biol Chem 1995;270:10822-7.
DOI: https://doi.org/10.1074/jbc.270.18.10822
Matsushita T, Meyer D, Sadler JE. Localization of von willebrand factor-binding sites for platelet glycoprotein Ib and botrocetin by charged-to-alanine scanning mutagenesis. J Biol Chem 2000;275:11044-9.
DOI: https://doi.org/10.1074/jbc.275.15.11044
Di Stasio E, Romitelli F, Lancellotti S, et al. Kinetic study of von Willebrand factor self-aggregation induced by ristocetin. Biophys Chem 2009;144:101-7.
DOI: https://doi.org/10.1016/j.bpc.2009.07.002
Papi M, Maulucci G, De Spirito M, et al. Ristocetin-induced Self-Aggregation of Von Willebrand Factor. Eur Biophys J 2010;39:1597-603.
DOI: https://doi.org/10.1007/s00249-010-0617-8
Di Stasio E, De Cristofaro R. The effect of shear stress on protein conformation: Physical forces operating on biochemical systems: The case of von Willebrand factor. Biophys Chem 2010;153:1-8.
DOI: https://doi.org/10.1016/j.bpc.2010.07.002
Montilla M, Hernandez-Ruiz L, Garcia-Cozar FJ, et al. Polyphosphate binds to human von Willebrand factor in vivo and modulates its interaction with glycoprotein Ib. J Thromb Haemost 2012;10:2315-23.
DOI: https://doi.org/10.1111/jth.12004
Tsai HM. Shear stress and von Willebrand factor in health and disease. Semin Thromb Hemost 2003;29:479-88.
DOI: https://doi.org/10.1055/s-2003-44556
Matsui T, Hamako J. Structure and function of snake venom toxins interacting with human von Willebrand factor. Toxicon 2005;45:1075-87.
DOI: https://doi.org/10.1016/j.toxicon.2005.02.023
Auton M, Sedlak E, Marek J, et al. Changes in thermodynamic stability of von Willebrand factor differentially affect the force-dependent binding to platelet GPIbalpha. Biophys J 2009;97:618-27.
DOI: https://doi.org/10.1016/j.bpj.2009.05.009
Scaglione GL, Lancellotti S, Papi M, et al. The type 2B p.R1306W natural mutation of von Willebrand factor dramatically enhances the multimer sensitivity to shear stress. J Thromb Haemost 2013;11:1688-98.
DOI: https://doi.org/10.1111/jth.12346
Federici AB, Mannucci PM, Castaman G, et al. Clinical and molecular predictors of thrombocytopenia and risk of bleeding in patients with von Willebrand disease type 2B: a cohort study of 67 patients. Blood 2009;113:526-34.
DOI: https://doi.org/10.1182/blood-2008-04-152280
Hickson N, Hampshire D, Winship P, et al. von Willebrand factor variant p.Arg924Gln marks an allele associated with reduced von Willebrand factor and factor VIII levels. J Thromb Haemost 2010;8:1986-93.
DOI: https://doi.org/10.1111/j.1538-7836.2010.03927.x
South K, Lane DA. ADAMTS-13 and von Willebrand factor: a dynamic duo. J Thromb Haemost 2018;16:6-18.
DOI: https://doi.org/10.1111/jth.13898
De Ceunynck K, Rocha S, Feys HB, et al. Local elongation of endothelial cell-anchored von Willebrand factor strings precedes ADAMTS13 protein-mediated proteolysis. J Biol Chem 2011;286:36361-7.
DOI: https://doi.org/10.1074/jbc.M111.271890
Gao W, Anderson PJ, Majerus EM, et al. Exosite interactions contribute to tension-induced cleavage of von Willebrand factor by the antithrombotic ADAMTS13 metalloprotease. Proc Natl Acad Sci U S A 2006;103:19099-104.
DOI: https://doi.org/10.1073/pnas.0607264104
Di Stasio E, Lancellotti S, Peyvandi F, et al. Mechanistic studies on ADAMTS13 catalysis. Biophys J 2008;95:2450-61.
DOI: https://doi.org/10.1529/biophysj.108.131532
Zhang C, Kelkar A, Neelamegham S. von Willebrand factor self-association is regulated by the shear-dependent unfolding of the A2 domain. Blood Adv 2019;3:957-68.
DOI: https://doi.org/10.1182/bloodadvances.2018030122
Rakshit S, Sivasankar S. Biomechanics of cell adhesion: how force regulates the lifetime of adhesive bonds at the single molecule level. Phys Chem Chem Phys 2014;16:2211-23.
DOI: https://doi.org/10.1039/c3cp53963f
Thomas WE, Vogel V, Sokurenko E. Biophysics of catch bonds. Annu Rev Biophys 2008;37:399-416.
DOI: https://doi.org/10.1146/annurev.biophys.37.032807.125804
McEver RP. Selectins: initiators of leucocyte adhesion and signalling at the vascular wall. Cardiovasc Res 2015;107:331-9.
DOI: https://doi.org/10.1093/cvr/cvv154
Manakova K, Yan H, Lowengrub J, Allard J. Cell Surface Mechanochemistry and the Determinants of Bleb Formation, Healing, and Travel Velocity. Biophys J 2016;110:1636-47.
DOI: https://doi.org/10.1016/j.bpj.2016.03.008
Strakova K, Assies L, Goujon A, et al. Dithienothiophenes at Work: Access to Mechanosensitive Fluorescent Probes, Chalcogen-Bonding Catalysis, and Beyond. Chem Rev 2019 Aug 15.
DOI: https://doi.org/10.1021/acs.chemrev.9b00279
Liu Z, Yago T, Zhang N, et al. L-selectin mechanochemistry restricts neutrophil priming in vivo. Nat Commun 2017;8:15196.
DOI: https://doi.org/10.1038/ncomms15196
Brooks DE, Trust TJ. Enhancement of bacterial adhesion by shear forces: characterization of the haemagglutination induced by Aeromonas salmonicida strain 438. J Gen Microbiol 1983;129:3661-9.
DOI: https://doi.org/10.1099/00221287-129-12-3661
Zheng X, Chung D, Takayama TK, et al. Structure of von Willebrand factor-cleaving protease (ADAMTS13), a metalloprotease involved in thrombotic thrombocytopenic purpura. J Biol Chem 2001;276:41059-63.
DOI: https://doi.org/10.1074/jbc.C100515200
Zanardelli S, Chion AC, Groot E, et al. A novel binding site for ADAMTS13 constitutively exposed on the surface of globular VWF. Blood 2009;114:2819-28.
DOI: https://doi.org/10.1182/blood-2009-05-224915
Kim HJ, Xu Y, Petri A, et al. Crystal structure of ADAMTS13 CUB domains reveals their role in global latency. Sci Adv 2021;7.
DOI: https://doi.org/10.1126/sciadv.abg4403
Petri A, Kim HJ, Xu Y, et al. Crystal structure and substrate-induced activation of ADAMTS13. Nat Commun 2019;10:3781.
DOI: https://doi.org/10.1038/s41467-019-11474-5
Tsai CJ, Nussinov R. A unified view of "how allostery works". PLoS Comput Biol 2014;10:e1003394.
DOI: https://doi.org/10.1371/journal.pcbi.1003394
Deforche L, Roose E, Vandenbulcke A, et al. Linker regions and flexibility around the metalloprotease domain account for conformational activation of ADAMTS-13. J Thromb Haemost 2015;13:2063-75.
DOI: https://doi.org/10.1111/jth.13149
Crawley JT, de Groot R, Xiang Y, et al. Unraveling the scissile bond: how ADAMTS13 recognizes and cleaves von Willebrand factor. Blood 2011;118:3212-21.
DOI: https://doi.org/10.1182/blood-2011-02-306597
Lancellotti S, Sacco M, Basso M, De Cristofaro R. Mechanochemistry of von Willebrand factor. Biomol Concepts 2019;10:194-208.
DOI: https://doi.org/10.1515/bmc-2019-0022
Yago T, Lou J, Wu T, et al. Platelet glycoprotein Ibalpha forms catch bonds with human WT vWF but not with type 2B von Willebrand disease vWF. J Clin Invest 2008;118:3195-207.
DOI: https://doi.org/10.1172/JCI35754
Colace TV, Diamond SL. Direct observation of von Willebrand factor elongation and fiber formation on collagen during acute whole blood exposure to pathological flow. Arterioscler Thromb Vasc Biol 2013;33:105-13.
DOI: https://doi.org/10.1161/ATVBAHA.112.300522
Ju L, Dong JF, Cruz MA, Zhu C. The N-terminal flanking region of the A1 domain regulates the force-dependent binding of von Willebrand factor to platelet glycoprotein Ibalpha. J Biol Chem 2013;288:32289-301.
DOI: https://doi.org/10.1074/jbc.M113.504001
Kim J, Zhang CZ, Zhang X, Springer TA. A mechanically stabilized receptor-ligand flex-bond important in the vasculature. Nature 2010;466:992-5.
DOI: https://doi.org/10.1038/nature09295
Bell GI. Models for the specific adhesion of cells to cells. Science 1978;200:618-27.
DOI: https://doi.org/10.1126/science.347575
Dembo M, Torney DC, Saxman K, Hammer D. The reaction-limited kinetics of membrane-to-surface adhesion and detachment. Proc R Soc Lond B Biol Sci 1988;234:55-83.
DOI: https://doi.org/10.1098/rspb.1988.0038
Machha VR, Tischer A, Moon-Tasson L, Auton M. The Von Willebrand Factor A1-Collagen III Interaction Is Independent of Conformation and Type 2 Von Willebrand Disease Phenotype. J Mol Biol 2017;429:32-47.
DOI: https://doi.org/10.1016/j.jmb.2016.11.014
Aponte-Santamaria C, Huck V, Posch S, et al. Force-sensitive autoinhibition of the von Willebrand factor is mediated by interdomain interactions. Biophys J 2015;108:2312-21.
DOI: https://doi.org/10.1016/j.bpj.2015.03.041
Fuchs B, Budde U, Schulz A, et al. Flow-based measurements of von Willebrand factor (VWF) function: binding to collagen and platelet adhesion under physiological shear rate. Thromb Res 2010;125:239-45. C.
DOI: https://doi.org/10.1016/j.thromres.2009.08.020
Favaloro EJ. Diagnosing von Willebrand disease: a short history of laboratory milestones and innovations, plus current status, challenges, and solutions. Semin Thromb Hemost 2014;40:551-70.
DOI: https://doi.org/10.1055/s-0034-1383546
Lagrange J, Worou ME, Michel JB, et al. The VWF/LRP4/alphaVbeta3-axis represents a novel pathway regulating proliferation of human vascular smooth muscle cells. Cardiovasc Res 2021 Feb 12.
DOI: https://doi.org/10.1093/cvr/cvab042
Reininger AJ, Heijnen HF, Schumann H, et al. Mechanism of platelet adhesion to von Willebrand factor and microparticle formation under high shear stress. Blood 2006;107:3537-45.
DOI: https://doi.org/10.1182/blood-2005-02-0618
Bryckaert M, Rosa JP, Denis CV, Lenting PJ. Of von Willebrand factor and platelets. Cell Mol Life Sci 2015;72:307-26.
DOI: https://doi.org/10.1007/s00018-014-1743-8
Kruse-Jarres R, Johnsen JM. How I treat type 2B von Willebrand disease. Blood 2018;131:1292-1300.
DOI: https://doi.org/10.1182/blood-2017-06-742692
Tischer A, Campbell JC, Machha VR, et al. Mutational Constraints on Local Unfolding Inhibit the Rheological Adaptation of von Willebrand Factor. J Biol Chem 2016;291:3848-59.
DOI: https://doi.org/10.1074/jbc.M115.703850
Springer TA. Complement and the multifaceted functions of VWA and integrin I domains. Structure 2006;14:1611-6.
DOI: https://doi.org/10.1016/j.str.2006.10.001
Valiaev A, Lim DW, Oas TG, et al. Force-induced prolyl cis-trans isomerization in elastin-like polypeptides. J Am Chem Soc 2007;129:6491-7..
DOI: https://doi.org/10.1021/ja070147r
Springer TA. von Willebrand factor, Jedi knight of the bloodstream. Blood 2014;124:1412-25.
DOI: https://doi.org/10.1182/blood-2014-05-378638
Shankaran H, Neelamegham S. Hydrodynamic forces applied on intercellular bonds, soluble molecules, and cell-surface receptors. Biophys J 2004;86:576-88.
DOI: https://doi.org/10.1016/S0006-3495(04)74136-3
Day MA. The no-slip condition of fluid dynamics. Springer Netherlands; 2004.
George JN, Nester CM. Syndromes of thrombotic microangiopathy. N Engl J Med 2014;371:1847-8.
DOI: https://doi.org/10.1056/NEJMc1410951
Fu H, Jiang Y, Yang D, et al. Flow-induced elongation of von Willebrand factor precedes tension-dependent activation. Nat Commun 2017;8:324.
DOI: https://doi.org/10.1038/s41467-017-00230-2
Saha M, McDaniel JK, Zheng XL. Thrombotic thrombocytopenic purpura: pathogenesis, diagnosis and potential novel therapeutics. J Thromb Haemost 2017;15:1889-900.
DOI: https://doi.org/10.1111/jth.13764
Bennett MJ, Schlunegger MP, Eisenberg D. 3D domain swapping: a mechanism for oligomer assembly. Protein Sci 1995;4:2455-68.
DOI: https://doi.org/10.1002/pro.5560041202
Liu Y, Eisenberg D. 3D domain swapping: as domains continue to swap. Protein Sci 2002;11:1285-99.
DOI: https://doi.org/10.1110/ps.0201402
de Groot R, Lane DA, Crawley JT. The ADAMTS13 metalloprotease domain: roles of subsites in enzyme activity and specificity. Blood 2010;116:3064-72.
DOI: https://doi.org/10.1182/blood-2009-12-258780
Favaloro EJ, Henry BM, Lippi G. Increased VWF and Decreased ADAMTS-13 in COVID-19: Creating a Milieu for (Micro)Thrombosis. Semin Thromb Hemost 2021;47:400-18.
DOI: https://doi.org/10.1055/s-0041-1727282
Taylor A, Vendramin C, Singh D, et al. von Willebrand factor/ADAMTS13 ratio at presentation of acute ischemic brain injury is predictive of outcome. Blood Adv 2020;4:398-407.
DOI: https://doi.org/10.1182/bloodadvances.2019000979
Denorme F, Kraft P, Pareyn I, et al. Reduced ADAMTS13 levels in patients with acute and chronic cerebrovascular disease. PLoS One 2017;12:e0179258.
DOI: https://doi.org/10.1371/journal.pone.0179258
Uemura M, Fujimura Y, Matsumoto M, et al. Comprehensive analysis of ADAMTS13 in patients with liver cirrhosis. Thromb Haemost 2008;99:1019-29.
DOI: https://doi.org/10.1160/TH08-01-0006
Kobayashi S, Yokoyama Y, Matsushita T, et al. Increased von Willebrand Factor to ADAMTS13 ratio as a predictor of thrombotic complications following a major hepatectomy. Arch Surg 2012;147:909-17.
DOI: https://doi.org/10.1001/archsurg.2012.998
Lancellotti S, Basso M, Veca V, et al. Presence of portal vein thrombosis in liver cirrhosis is strongly associated with low levels of ADAMTS-13: a pilot study. Intern Emerg Med 2016;11:959-67.
DOI: https://doi.org/10.1007/s11739-016-1467-x
Matsukawa M, Kaikita K, Soejima K, et al. Serial changes in von Willebrand factor-cleaving protease (ADAMTS13) and prognosis after acute myocardial infarction. Am J Cardiol 2007;100:758-63.
DOI: https://doi.org/10.1016/j.amjcard.2007.03.095
Joly BS, Darmon M, Dekimpe C, et al. Imbalance of von Willebrand factor and ADAMTS13 axis is rather a biomarker of strong inflammation and endothelial damage than a cause of thrombotic process in critically ill COVID-19 patients. J Thromb Haemost 2021;19:2193-8.
DOI: https://doi.org/10.1111/jth.15445
Bazzan M, Montaruli B, Sciascia S, et al. Low ADAMTS 13 plasma levels are predictors of mortality in COVID-19 patients. Intern Emerg Med 2020;15:861-3.
DOI: https://doi.org/10.1007/s11739-020-02394-0
De Cristofaro R, Liuzzo G, Sacco M, et al. Marked von Willebrand factor and factor VIII elevations in severe acute respiratory syndrome coronavirus-2-positive, but not severe acute respiratory syndrome coronavirus-2-negative, pneumonia: a case-control study. Blood Coagul Fibrinolysis 2021;32:285-9.
DOI: https://doi.org/10.1097/MBC.0000000000000998
Bowen DJ. An influence of ABO blood group on the rate of proteolysis of von Willebrand factor by ADAMTS13. J Thromb Haemost 2003;1:33-40.
DOI: https://doi.org/10.1046/j.1538-7836.2003.00007.x
Lynch CJ, Cawte AD, Millar CM, et al. A common mechanism by which type 2A von Willebrand disease mutations enhance ADAMTS13 proteolysis revealed with a von Willebrand factor A2 domain FRET construct. PLoS One 2017;12:e0188405.
DOI: https://doi.org/10.1371/journal.pone.0188405
Meyer AL, Malehsa D, Bara C, et al. Acquired von Willebrand syndrome in patients with an axial flow left ventricular assist device. Circ Heart Fail 2010;3:675-81.
DOI: https://doi.org/10.1161/CIRCHEARTFAILURE.109.877597
Lee M, Rodansky ES, Smith JK, Rodgers GM. ADAMTS13 promotes angiogenesis and modulates VEGF-induced angiogenesis. Microvasc Res 2012;84:109-15.
DOI: https://doi.org/10.1016/j.mvr.2012.05.004
Qin F, Impeduglia T, Schaffer P, Dardik H. Overexpression of von Willebrand factor is an independent risk factor for pathogenesis of intimal hyperplasia: preliminary studies. J Vasc Surg 2003;37:433-9.
DOI: https://doi.org/10.1067/mva.2003.63
Ishihara J, Ishihara A, Starke RD, et al. The heparin binding domain of von Willebrand factor binds to growth factors and promotes angiogenesis in wound healing. Blood 2019;133:2559-69.
DOI: https://doi.org/10.1182/blood.2019000510
Starke RD, Ferraro F, Paschalaki KE, et al. Endothelial von Willebrand factor regulates angiogenesis. Blood 2011;117:1071-80.
DOI: https://doi.org/10.1182/blood-2010-01-264507
Lee M, Keener J, Xiao J, et al. ADAMTS13 and its variants promote angiogenesis via upregulation of VEGF and VEGFR2. Cell Mol Life Sci 2015;72:349-56.
DOI: https://doi.org/10.1007/s00018-014-1667-3
Hugenholtz GC, Adelmeijer J, Meijers JC, et al. An unbalance between von Willebrand factor and ADAMTS13 in acute liver failure: implications for hemostasis and clinical outcome. Hepatology 2013;58:752-61.
DOI: https://doi.org/10.1002/hep.26372
Seth R, McKinnon TAJ, Zhang XF. Contribution of the von Willebrand factor/ADAMTS13 imbalance to COVID-19 coagulopathy. Am J Physiol Heart Circ Physiol 2022;322:H87-H93.
DOI: https://doi.org/10.1152/ajpheart.00204.2021
How to Cite
Lancellotti, S. ., Sacco, M. ., Tardugno, M. ., Ferretti, A. ., & De Cristofaro, R. . (2022). The Von Willebrand factor-ADAMTS-13 axis: a two-faced Janus in bleeding and thrombosis. Bleeding, Thrombosis and Vascular Biology, 1(1). https://doi.org/10.4081/btvb.2022.11
Copyright (c) 2022 The Author(s)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.
Most read articles by the same author(s)
- Giovanni Di Minno, Gaia Spadarella, Ilenia Lorenza Calcaterra, Giancarlo Castaman, Paolo Simioni, Raimondo De Cristofaro, Cristina Santoro, Flora Peyvandi, Matteo Di Minno, The evolving landscape of gene therapy for congenital severe hemophilia: a 2024 state of the art , Bleeding, Thrombosis and Vascular Biology: Vol. 3 No. 2 (2024)
Similar Articles
- Juan Eirís, Marina Suárez-Terrón, Pablo Granados, David Martínez-Campuzano, Ana Rosa Cid, Saturnino Haya, Santiago Bonanad, Allopurinol-induced acquired von Willebrand syndrome , Bleeding, Thrombosis and Vascular Biology: Vol. 2 No. 4 (2023)
- Giovanni L. Tiscia, Donatella Colaizzo, Antonio De Laurenzo, Filomena Cappucci, Lucia Fischetti, Elena Chinni, Mario Mastroianno, Giovanni Favuzzi, Massimo Carella, Elvira Grandone, Thrombin generation assay in COVID-19 patients shows a hypocoagulable pattern , Bleeding, Thrombosis and Vascular Biology: Vol. 3 No. 3 (2024)
- Boris Shenkman, Ivan Budnik, Yulia Einav, Interaction between adenosine diphosphate receptors and protein-kinase C isoforms in platelet adhesion under flow condition , Bleeding, Thrombosis and Vascular Biology: Vol. 2 No. 1 (2023)
- Francesca Santilli, Paola Simeone, Rossella Liani, Inflammation, platelets and diabetes , Bleeding, Thrombosis and Vascular Biology: Vol. 2 No. 2 (2023)
- Daniela Poli, Riccardo Tartaglia, Doris Barcellona , Paolo Bucciarelli , Antonio Ciampa, Elvira Grandone, Giuseppe Malcangi, Giuseppe Rescigno, Vincenzo Toschi, Sophie Testa, Alessandro Squizzato, Attitude to clinical research among health professionals affiliated with the Italian Federation of Centers for the Diagnosis of Thrombotic Disorders and the Surveillance of the Antithrombotic Therapies (FCSA) , Bleeding, Thrombosis and Vascular Biology: Vol. 2 No. 1 (2023)
- Luca D'Ambrosio, Maurizio Forte, Giacomo Frati, Sebastiano Sciarretta, Role of platelet autophagy in cardiovascular diseases , Bleeding, Thrombosis and Vascular Biology: Vol. 3 No. 2 (2024)
- Domenico Prisco, Irene Mattioli, Raffaele De Caterina, Alessandra Bettiol, The new era of anticoagulation: factor XI and XII inhibitors , Bleeding, Thrombosis and Vascular Biology: Vol. 2 No. 2 (2023)
- Vincenzo Sammartano, Adele Santoni, Elisabetta Zappone, Paola Calzoni, Daniela Fineschi, Eleonora Franceschini, Federico Caroni, Anna Sicuranza, Monica Bocchia, Luca Puccetti, A case of acquired factor XIII deficiency secondary to plasmablastic lymphoma , Bleeding, Thrombosis and Vascular Biology: Vol. 2 No. 1 (2023)
- Marcello Di Nisio, Matteo Candeloro, Nicola Potere, Ettore Porreca, Jeffrey I. Weitz, Factor XI inhibitors: a new option for the prevention and treatment of cancer-associated thrombosis , Bleeding, Thrombosis and Vascular Biology: Vol. 3 No. s1 (2024): 12th ICTHIC
- Stefania Momi, Paolo Gresele, Blood platelets and Charles Darwin’s natural selection , Bleeding, Thrombosis and Vascular Biology: Vol. 2 No. 1 (2023)
You may also start an advanced similarity search for this article.
