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Semin Thromb Hemost 2010; 36(1): 071-081
DOI: 10.1055/s-0030-1248726
© Thieme Medical PublishersDOI: 10.1055/s-0030-1248726
Von Willebrand Factor, ADAMTS-13, and Thrombotic Thrombocytopenic Purpura
Weitere Informationen
Publikationsverlauf
Publikationsdatum:
13. April 2010 (online)
ABSTRACT
For a disease with <80 years of history, clinical and basic research into thrombotic thrombocytopenic purpura (TTP) has been significantly accelerated since the identification of unusually large von Willebrand factor (VWF) multimers and deficiency of ADAMTS-13 (A Disintegrin And Metalloproteinase with Thrombospondin-1-like domains) as the potential cause. The VWF-cleaving metalloprotease ADAMTS-13 has since been extensively characterized and its biological action tested in vitro and in vivo. There have also been considerable efforts to understand the interaction between ADAMTS-13 and its substrate VWF, as well as its biological regulation. This review focuses on recent advances in our understanding of the biology of VWF cleavage by ADAMTS-13 and how this newly gained knowledge will eventually help the clinical management of patients with TTP. This review also discusses the potential for ADAMTS-13 as a therapeutic drug for thrombotic conditions other than TTP.
KEYWORDS
von Willebrand factor - ADAMTS-13 - fluid shear stress - thrombotic thrombocytopenic purpura - TTP
REFERENCES
- 1 Moschcowitz E. Hyaline thrombosis of the terminal arterioles and capillaries: a hitherto undescribed disease. Proc N Y Pathol Soc. 1924; 24 21
- 2 Amorosi E L, Ultamann J E. Thrombocytopenic purpura: report of 16 cases and review of the literature. Medicine. 1966; 45 139-159
- 3 Moake J L, Rudy C K, Troll J H et al.. Unusually large plasma factor VIII:von Willebrand factor multimers in chronic relapsing thrombotic thrombocytopenic purpura. N Engl J Med. 1982; 307(23) 1432-1435
- 4 Moake J L, Turner N A, Stathopoulos N A, Nolasco L H, Hellums J D. Involvement of large plasma von Willebrand factor (VWF) multimers and unusually large VWF forms derived from endothelial cells in shear stress-induced platelet aggregation. J Clin Invest. 1986; 78(6) 1456-1461
- 5 Moake J L, Turner N A, Stathopoulos N A, Nolasco L, Hellums J D. Shear-induced platelet aggregation can be mediated by VWF released from platelets, as well as by exogenous large or unusually large VWF multimers, requires adenosine diphosphate, and is resistant to aspirin. Blood. 1988; 71(5) 1366-1374
- 6 Arya M, Anvari B, Romo G M et al.. Ultralarge multimers of von Willebrand factor form spontaneous high-strength bonds with the platelet glycoprotein Ib-IX complex: studies using optical tweezers. Blood. 2002; 99(11) 3971-3977
- 7 Furlan M, Robles R, Lämmle B. Partial purification and characterization of a protease from human plasma cleaving von Willebrand factor to fragments produced by in vivo proteolysis. Blood. 1996; 87(10) 4223-4234
- 8 Tsai H M. Physiologic cleavage of von Willebrand factor by a plasma protease is dependent on its conformation and requires calcium ion. Blood. 1996; 87(10) 4235-4244
- 9 Fujikawa K, Suzuki H, McMullen B, Chung D. Purification of human von Willebrand factor-cleaving protease and its identification as a new member of the metalloproteinase family. Blood. 2001; 98(6) 1662-1666
- 10 Levy G G, Nichols W C, Lian E C et al.. Mutations in a member of the ADAMTS gene family cause thrombotic thrombocytopenic purpura. Nature. 2001; 413(6855) 488-494
- 11 Zheng X, Chung D, Takayama T K, Majerus E M, Sadler J E, Fujikawa K. Structure of von Willebrand factor-cleaving protease (ADAMTS13), a metalloprotease involved in thrombotic thrombocytopenic purpura. J Biol Chem. 2001; 276(44) 41059-41063
- 12 Furlan M, Robles R, Solenthaler M, Lämmle B. Acquired deficiency of von Willebrand factor-cleaving protease in a patient with thrombotic thrombocytopenic purpura. Blood. 1998; 91(8) 2839-2846
- 13 Tsai H M, Lian E C. Antibodies to von Willebrand factor-cleaving protease in acute thrombotic thrombocytopenic purpura. N Engl J Med. 1998; 339(22) 1585-1594
- 14 Scheiflinger F, Knöbl P, Trattner B et al.. Nonneutralizing IgM and IgG antibodies to von Willebrand factor-cleaving protease (ADAMTS-13) in a patient with thrombotic thrombocytopenic purpura. Blood. 2003; 102(9) 3241-3243
- 15 Weibel E R, Palade G E. New cytoplasmic components in arterial endothelia. J Cell Biol. 1964; 23 101-112
- 16 Bowie E J, Solberg Jr L A, Fass D N et al.. Transplantation of normal bone marrow into a pig with severe von Willebrand’s disease. J Clin Invest. 1986; 78(1) 26-30
- 17 Ginsburg D, Handin R I, Bonthron D T et al.. Human von Willebrand factor (VWF): isolation of complementary DNA (cDNA) clones and chromosomal localization. Science. 1985; 228(4706) 1401-1406
- 18 Wagner D D, Marder V J. Biosynthesis of von Willebrand protein by human endothelial cells: processing steps and their intracellular localization. J Cell Biol. 1984; 99(6) 2123-2130
- 19 Wagner D D, Lawrence S O, Ohlsson-Wilhelm B M, Fay P J, Marder V J. Topology and order of formation of interchain disulfide bonds in von Willebrand factor. Blood. 1987; 69(1) 27-32
- 20 Voorberg J, Fontijn R, Calafat J, Janssen H, van Mourik J A, Pannekoek H. Assembly and routing of von Willebrand factor variants: the requirements for disulfide-linked dimerization reside within the carboxy-terminal 151 amino acids. J Cell Biol. 1991; 113(1) 195-205
- 21 Katsumi A, Tuley E A, Bodó I, Sadler J E. Localization of disulfide bonds in the cystine knot domain of human von Willebrand factor. J Biol Chem. 2000; 275(33) 25585-25594
- 22 Purvis A R, Gross J, Dang L T et al.. Two Cys residues essential for von Willebrand factor multimer assembly in the Golgi. Proc Natl Acad Sci U S A. 2007; 104(40) 15647-15652
- 23 Wagner D D, Fay P J, Sporn L A, Sinha S, Lawrence S O, Marder V J. Divergent fates of von Willebrand factor and its propolypeptide (von Willebrand antigen II) after secretion from endothelial cells. Proc Natl Acad Sci U S A. 1987; 84(7) 1955-1959
- 24 Verweij C L, Hart M, Pannekoek H. Expression of variant von Willebrand factor (VWF) cDNA in heterologous cells: requirement of the pro-polypeptide in VWF multimer formation. EMBO J. 1987; 6(10) 2885-2890
- 25 Wise R J, Pittman D D, Handin R I, Kaufman R J, Orkin S H. The propeptide of von Willebrand factor independently mediates the assembly of von Willebrand multimers. Cell. 1988; 52(2) 229-236
- 26 Sporn L A, Marder V J, Wagner D D. Inducible secretion of large, biologically potent von Willebrand factor multimers. Cell. 1986; 46(2) 185-190
- 27 Mannucci P M. Platelet von Willebrand factor in inherited and acquired bleeding disorders. Proc Natl Acad Sci U S A. 1995; 92(7) 2428-2432
- 28 Huang R H, Wang Y, Roth R et al.. Assembly of Weibel-Palade body-like tubules from N-terminal domains of von Willebrand factor. Proc Natl Acad Sci U S A. 2008; 105(2) 482-487
- 29 Berriman J A, Li S, Hewlett L J et al.. Structural organization of Weibel-Palade bodies revealed by cryo-EM of vitrified endothelial cells. Proc Natl Acad Sci U S A. 2009; 106(41) 17407-17412
- 30 Michaux G, Abbitt K B, Collinson L M, Haberichter S L, Norman K E, Cutler D F. The physiological function of von Willebrand’s factor depends on its tubular storage in endothelial Weibel-Palade bodies. Dev Cell. 2006; 10(2) 223-232
- 31 Schorer A E, Moldow C F, Rick M E. Interleukin 1 or endotoxin increases the release of von Willebrand factor from human endothelial cells. Br J Haematol. 1987; 67(2) 193-197
- 32 Paleolog E M, Crossman D C, McVey J H, Pearson J D. Differential regulation by cytokines of constitutive and stimulated secretion of von Willebrand factor from endothelial cells. Blood. 1990; 75(3) 688-695
- 33 Padilla A, Moake J L, Bernardo A et al.. P-selectin anchors newly released ultralarge von Willebrand factor multimers to the endothelial cell surface. Blood. 2004; 103(6) 2150-2156
- 34 Huang J, Roth R, Heuser J E, Sadler J E. Integrin alpha(v)beta(3) on human endothelial cells binds von Willebrand factor strings under fluid shear stress. Blood. 2009; 113(7) 1589-1597
- 35 Chauhan A K, Goerge T, Schneider S W, Wagner D D. Formation of platelet strings and microthrombi in the presence of ADAMTS-13 inhibitor does not require P-selectin or beta3 integrin. J Thromb Haemost. 2007; 5(3) 583-589
- 36 Dong J F, Moake J L, Nolasco L et al.. ADAMTS-13 rapidly cleaves newly secreted ultralarge von Willebrand factor multimers on the endothelial surface under flowing conditions. Blood. 2002; 100(12) 4033-4039
- 37 Bernardo A, Ball C, Nolasco L, Choi H, Moake J L, Dong J F. Platelets adhered to endothelial cell-bound ultra-large von Willebrand factor strings support leukocyte tethering and rolling under high shear stress. J Thromb Haemost. 2005; 3(3) 562-570
- 38 Groot E, Fijnheer R, Sebastian S A, de Groot P G, Lenting P J. The active conformation of von Willebrand factor in patients with thrombotic thrombocytopenic purpura in remission. J Thromb Haemost. 2009; 7(6) 962-969
- 39 Martin C, Morales L D, Cruz M A. Purified A2 domain of von Willebrand factor binds to the active conformation of von Willebrand factor and blocks the interaction with platelet glycoprotein Ibalpha. J Thromb Haemost. 2007; 5(7) 1363-1370
- 40 Siedlecki C A, Lestini B J, Kottke-Marchant K K, Eppell S J, Wilson D L, Marchant R E. Shear-dependent changes in the three-dimensional structure of human von Willebrand factor. Blood. 1996; 88(8) 2939-2950
- 41 Shankaran H, Alexandridis P, Neelamegham S. Aspects of hydrodynamic shear regulating shear-induced platelet activation and self-association of von Willebrand factor in suspension. Blood. 2003; 101(7) 2637-2645
- 42 Schneider S W, 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(19) 7899-7903
- 43 Choi H, Aboulfatova K, Pownall H J, Cook R, Dong J F. Shear-induced disulfide bond formation regulates adhesion activity of von Willebrand factor. J Biol Chem. 2007; 282(49) 35604-35611
- 44 Li Y, Choi H, Zhou Z et al.. Covalent regulation of ULVWF string formation and elongation on endothelial cells under flow conditions. J Thromb Haemost. 2008; 6(7) 1135-1143
- 45 Xie L, Chesterman C N, Hogg P J. Reduction of von Willebrand factor by endothelial cells. Thromb Haemost. 2000; 84(3) 506-513
- 46 Xie L, Chesterman C N, Hogg P J. Control of von Willebrand factor multimer size by thrombospondin-1. J Exp Med. 2001; 193(12) 1341-1349
- 47 Pimanda J E, Annis D S, Raftery M, Mosher D F, Chesterman C N, Hogg P J. The von Willebrand factor-reducing activity of thrombospondin-1 is located in the calcium-binding/C-terminal sequence and requires a free thiol at position 974. Blood. 2002; 100(8) 2832-2838
- 48 Chen J, Fu X, Wang Y et al.. Oxidative modification of von Willebrand factor by neutrophil oxidants inhibits its cleavage by ADAMTS13. Blood. 2009; , October 7 (Epub ahead of print)
- 49 Porter S, Clark I M, Kevorkian L, Edwards D R. The ADAMTS metalloproteinases. Biochem J. 2005; 386(Pt 1) 15-27
- 50 Anderson P J, Kokame K, Sadler J E. Zinc and calcium ions cooperatively modulate ADAMTS13 activity. J Biol Chem. 2006; 281(2) 850-857
- 51 Gardner M D, Chion C K, de Groot R, Shah A, Crawley J T, Lane D A. A functional calcium-binding site in the metalloprotease domain of ADAMTS13. Blood. 2009; 113(5) 1149-1157
- 52 Mannucci P M, Canciani M T, Forza I, Lussana F, Lattuada A, Rossi E. Changes in health and disease of the metalloprotease that cleaves von Willebrand factor. Blood. 2001; 98(9) 2730-2735
- 53 Tsai H M, Sarode R, Downes K A. Ultralarge von Willebrand factor multimers and normal ADAMTS13 activity in the umbilical cord blood. Thromb Res. 2002; 108(2–3) 121-125
- 54 Uemura M, Tatsumi K, Matsumoto M et al.. Localization of ADAMTS13 to the stellate cells of human liver. Blood. 2005; 106(3) 922-924
- 55 Zhou W, Inada M, Lee T P et al.. ADAMTS13 is expressed in hepatic stellate cells. Lab Invest. 2005; 85(6) 780-788
- 56 Suzuki M, Murata M, Matsubara Y et al.. Detection of von Willebrand factor-cleaving protease (ADAMTS-13) in human platelets. Biochem Biophys Res Commun. 2004; 313(1) 212-216
- 57 Liu L, Choi H, Bernardo A et al.. Platelet-derived VWF-cleaving metalloprotease ADAMTS-13. J Thromb Haemost. 2005; 3(11) 2536-2544
- 58 Turner N, Nolasco L, Tao Z, Dong J F, Moake J. Human endothelial cells synthesize and release ADAMTS-13. J Thromb Haemost. 2006; 4(6) 1396-1404
- 59 Davis A K, Makar R S, Stowell C P, Kuter D J, Dzik W H. ADAMTS13 binds to CD36: a potential mechanism for platelet and endothelial localization of ADAMTS13. Transfusion. 2009; 49(2) 206-213
- 60 Vomund A N, Majerus E M. ADAMTS13 bound to endothelial cells exhibits enhanced cleavage of von Willebrand factor. J Biol Chem. 2009; 284(45) 30925-30932
- 61 Turner N A, Nolasco L, Ruggeri Z M, Moake J L. Endothelial cell ADAMTS-13 and VWF: production, release and VWF string cleavage. Blood. 2009; 114(24) 5102-5111
- 62 Shang D, Zheng X W, Niiya M, Zheng X L. Apical sorting of ADAMTS13 in vascular endothelial cells and Madin-Darby canine kidney cells depends on the CUB domains and their association with lipid rafts. Blood. 2006; 108(7) 2207-2215
- 63 Zhou Z, Jing H, Tao Z et al.. Effects of naturally occurring mutations in CUB-1 domain on synthesis, stability, and activity of ADAMTS-13. Thromb Res. 2009; 124(3) 323-327
- 64 Ricketts L M, Dlugosz M, Luther K B, Haltiwanger R S, Majerus E M. O-fucosylation is required for ADAMTS13 secretion. J Biol Chem. 2007; 282(23) 17014-17023
- 65 Zhou W, Tsai H M. N-Glycans of ADAMTS13 modulate its secretion and von Willebrand factor cleaving activity. Blood. 2009; 113(4) 929-935
- 66 Cao W J, Niiya M, Zheng X W, Shang D Z, Zheng X L. Inflammatory cytokines inhibit ADAMTS13 synthesis in hepatic stellate cells and endothelial cells. J Thromb Haemost. 2008; 6(7) 1233-1235
- 67 Nguyen T C, Liu A, Liu L et al.. Acquired ADAMTS-13 deficiency in pediatric patients with severe sepsis. Haemtologica. 2007; 92 121-124
- 68 Kremer Hovinga J A, Zeerleder S, Kessler P et al.. ADAMTS-13, von Willebrand factor and related parameters in severe sepsis and septic shock. J Thromb Haemost. 2007; 5(11) 2284-2290
- 69 Zheng X, Nishio K, Majerus E M, Sadler J E. Cleavage of von Willebrand factor requires the spacer domain of the metalloprotease ADAMTS13. J Biol Chem. 2003; 278(32) 30136-30141
- 70 Majerus E M, Anderson P J, Sadler J E. Binding of ADAMTS13 to von Willebrand factor. J Biol Chem. 2005; 280(23) 21773-21778
- 71 Zhou W, Dong L, Ginsburg D, Bouhassira E E, Tsai H M. Enzymatically active ADAMTS13 variants are not inhibited by anti-ADAMTS13 autoantibodies: a novel therapeutic strategy?. J Biol Chem. 2005; 280(48) 39934-39941
- 72 Feys H B, Anderson P J, Vanhoorelbeke K, Majerus E M, Sadler J E. Multi-step binding of ADAMTS13 to VWF. J Thromb Haemost. 2009; 7(12) 2088-2095
- 73 Soejima K, Matsumoto M, Kokame K et al.. ADAMTS-13 cysteine-rich/spacer domains are functionally essential for von Willebrand factor cleavage. Blood. 2003; 102(9) 3232-3237
- 74 Ai J, Smith P, Wang S, Zhang P, Zheng X L. The proximal carboxyl-terminal domains of ADAMTS13 determine substrate specificity and are all required for cleavage of von Willebrand factor. J Biol Chem. 2005; 280(33) 29428-29434
- 75 Gao W, Anderson P J, Majerus E M, Tuley E A, Sadler J E. 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(50) 19099-19104
- 76 de Groot R, Bardhan A, Ramroop N, Lane D A, Crawley J T. Essential role of the disintegrin-like domain in ADAMTS13 function. Blood. 2009; 113(22) 5609-5616
- 77 Zhang P, Pan W, Rux A H, Sachais B S, Zheng X L. The cooperative activity between the carboxyl-terminal TSP1 repeats and the CUB domains of ADAMTS13 is crucial for recognition of von Willebrand factor under flow. Blood. 2007; 110(6) 1887-1894
- 78 Tao Z, Peng Y, Nolasco L et al.. Recombinant CUB-1 domain polypeptide inhibits the cleavage of ULVWF strings by ADAMTS13 under flow conditions. Blood. 2005; 106(13) 4139-4145
- 79 Tao Z, Wang Y, Choi H et al.. Cleavage of ultralarge multimers of von Willebrand factor by C-terminal-truncated mutants of ADAMTS-13 under flow. Blood. 2005; 106(1) 141-143
- 80 Akiyama M, Takeda S, Kokame K, Takagi J, Miyata T. Crystal structures of the noncatalytic domains of ADAMTS13 reveal multiple discontinuous exosites for von Willebrand factor. Proc Natl Acad Sci U S A. 2009; 106(46) 19274-19279
- 81 Dong J F, Moake J L, Bernardo A et al.. ADAMTS-13 metalloprotease interacts with the endothelial cell-derived ultra-large von Willebrand factor. J Biol Chem. 2003; 278(32) 29633-29639
- 82 Kokame K, Matsumoto M, Fujimura Y, Miyata T. VWF73, a region from D1596 to R1668 of von Willebrand factor, provides a minimal substrate for ADAMTS-13. Blood. 2004; 103(2) 607-612
- 83 Wu J J, Fujikawa K, McMullen B A, Chung D W. Characterization of a core binding site for ADAMTS-13 in the A2 domain of von Willebrand factor. Proc Natl Acad Sci U S A. 2006; 103(49) 18470-18474
- 84 Zanardelli S, Crawley J T, Chion C K, Lam J K, Preston R J, Lane D A. ADAMTS13 substrate recognition of von Willebrand factor A2 domain. J Biol Chem. 2006; 281(3) 1555-1563
- 85 Jenkins P V, Pasi K J, Perkins S J. Molecular modeling of ligand and mutation sites of the type A domains of human von Willebrand factor and their relevance to von Willebrand’s disease. Blood. 1998; 91(6) 2032-2044
- 86 Tsai H M, Sussman I I, Nagel R L. Shear stress enhances the proteolysis of von Willebrand factor in normal plasma. Blood. 1994; 83(8) 2171-2179
- 87 Tsai H M. Shear stress and von Willebrand factor in health and disease. Semin Thromb Hemost. 2003; 29(5) 479-488
- 88 Baldauf C, Schneppenheim R, Stacklies W, et al.. Shear-induced unfolding activates von Willebrand factor A2 domain for proteolysis. J Thromb Haemost. 2009; 7(12) 2096-2105
- 89 Zhang X, Halvorsen K, Zhang C Z, Wong W P, Springer T A. Mechanoenzymatic cleavage of the ultralarge vascular protein von Willebrand factor. Science. 2009; 324(5932) 1330-1334
- 90 Wu T, Lin J, Cruz M A, Dong J F, Zhu C. Force-induced cleavage of single VWF A1A2A3-tridomains by ADAMTS-13. Blood. 2010; 115(2) 370-378
- 91 Nishio K, Anderson P J, Zheng X L, Sadler J E. Binding of platelet glycoprotein Ibalpha to von Willebrand factor domain A1 stimulates the cleavage of the adjacent domain A2 by ADAMTS13. Proc Natl Acad Sci U S A. 2004; 101(29) 10578-10583
- 92 Shim K, Anderson P J, Tuley E A, Wiswall E, Sadler J E. Platelet-VWF complexes are preferred substrates of ADAMTS13 under fluid shear stress. Blood. 2008; 111(2) 651-657
- 93 Cao W, Krishnaswamy S, Camire R M, Lenting P J, Zheng X L. Factor VIII accelerates proteolytic cleavage of von Willebrand factor by ADAMTS13. Proc Natl Acad Sci U S A. 2008; 105(21) 7416-7421
- 94 Zanardelli S, Chion A C, Groot E et al.. A novel binding site for ADAMTS13 constitutively exposed on the surface of globular VWF. Blood. 2009; 114(13) 2819-2828
- 95 Franchini M, Montagnana M, Targher G, Lippi G. Reduced von Willebrand factor-cleaving protease levels in secondary thrombotic microangiopathies and other diseases. Semin Thromb Hemost. 2007; 33(8) 787-797
- 96 Furlan M, Robles R, Solenthaler M, Wassmer M, Sandoz P, Lämmle B. Deficient activity of von Willebrand factor-cleaving protease in chronic relapsing thrombotic thrombocytopenic purpura. Blood. 1997; 89(9) 3097-3103
- 97 Furlan M, Robles R, Galbusera M et al.. von Willebrand factor-cleaving protease in thrombotic thrombocytopenic purpura and the hemolytic-uremic syndrome. N Engl J Med. 1998; 339(22) 1578-1584
- 98 Furlan M, Robles R, Morselli B, Sandoz P, Lämmle B. Recovery and half-life of von Willebrand factor-cleaving protease after plasma therapy in patients with thrombotic thrombocytopenic purpura. Thromb Haemost. 1999; 81(1) 8-13
- 99 Kokame K, Matsumoto M, Soejima K et al.. Mutations and common polymorphisms in ADAMTS13 gene responsible for von Willebrand factor-cleaving protease activity. Proc Natl Acad Sci U S A. 2002; 99(18) 11902-11907
- 100 Antoine G, Zimmermann K, Plaimauer B et al.. ADAMTS13 gene defects in two brothers with constitutional thrombotic thrombocytopenic purpura and normalization of von Willebrand factor-cleaving protease activity by recombinant human ADAMTS13. Br J Haematol. 2003; 120(5) 821-824
- 101 Assink K, Schiphorst R, Allford S et al.. Mutation analysis and clinical implications of von Willebrand factor-cleaving protease deficiency. Kidney Int. 2003; 63(6) 1995-1999
- 102 Savasan S, Lee S K, Ginsburg D, Tsai H M. ADAMTS13 gene mutation in congenital thrombotic thrombocytopenic purpura with previously reported normal VWF cleaving protease activity. Blood. 2003; 101(11) 4449-4451
- 103 Schneppenheim R, Budde U, Oyen F et al.. von Willebrand factor cleaving protease and ADAMTS13 mutations in childhood TTP. Blood. 2003; 101(5) 1845-1850
- 104 Matsumoto M, Kokame K, Soejima K et al.. Molecular characterization of ADAMTS13 gene mutations in Japanese patients with Upshaw-Schulman syndrome. Blood. 2004; 103(4) 1305-1310
- 105 Licht C, Stapenhorst L, Simon T, Budde U, Schneppenheim R, Hoppe B. Two novel ADAMTS13 gene mutations in thrombotic thrombocytopenic purpura/hemolytic-uremic syndrome (TTP/HUS). Kidney Int. 2004; 66(3) 955-958
- 106 Uchida T, Wada H, Mizutani M Research Project on Genetics of Thrombosis et al. Identification of novel mutations in ADAMTS13 in an adult patient with congenital thrombotic thrombocytopenic purpura. Blood. 2004; 104(7) 2081-2083
- 107 Pimanda J E, Maekawa A, Wind T, Paxton J, Chesterman C N, Hogg P J. Congenital thrombotic thrombocytopenic purpura in association with a mutation in the second CUB domain of ADAMTS13. Blood. 2004; 103(2) 627-629
- 108 Furlan M, Lämmle B. Aetiology and pathogenesis of thrombotic thrombocytopenic purpura and haemolytic uraemic syndrome: the role of von Willebrand factor-cleaving protease. Best Pract Res Clin Haematol. 2001; 14(2) 437-454
- 109 Tao Z, Anthony K, Peng Y et al.. Novel ADAMTS-13 mutations in an adult with delayed onset thrombotic thrombocytopenic purpura. J Thromb Haemost. 2006; 4(9) 1931-1935
- 110 Motto D G, Chauhan A K, Zhu G et al.. Shigatoxin triggers thrombotic thrombocytopenic purpura in genetically susceptible ADAMTS13-deficient mice. J Clin Invest. 2005; 115(10) 2752-2761
- 111 Karmali M A, Steele B T, Petric M, Lim C. Sporadic cases of haemolytic-uraemic syndrome associated with faecal cytotoxin and cytotoxin-producing Escherichia coli in stools. Lancet. 1983; 1(8325) 619-620
- 112 Nolasco L H, Turner N A, Bernardo A et al.. Hemolytic uremic syndrome-associated Shiga toxins promote endothelial-cell secretion and impair ADAMTS13 cleavage of unusually large von Willebrand factor multimers. Blood. 2005; 106(13) 4199-4209
- 113 Chauhan A K, Walsh M T, Zhu G, Ginsburg D, Wagner D D, Motto D G. The combined roles of ADAMTS13 and VWF in murine models of TTP, endotoxemia, and thrombosis. Blood. 2008; 111(7) 3452-3457
- 114 Studt J D, Hovinga J A, Antoine G et al.. Fatal congenital thrombotic thrombocytopenic purpura with apparent ADAMTS13 inhibitor: in vitro inhibition of ADAMTS13 activity by hemoglobin. Blood. 2005; 105(2) 542-544
- 115 Donadelli R, Banterla F, Galbusera M International Registry of Recurrent and Familial HUS/TTP et al. In-vitro and in-vivo consequences of mutations in the von Willebrand factor cleaving protease ADAMTS13 in thrombotic thrombocytopenic purpura. Thromb Haemost. 2006; 96(4) 454-464
- 116 Kokame K, Miyata T. Genetic defects leading to hereditary thrombotic thrombocytopenic purpura. Semin Hematol. 2004; 41(1) 34-40
- 117 Plaimauer B, Fuhrmann J, Mohr G et al.. Modulation of ADAMTS13 secretion and specific activity by a combination of common amino acid polymorphisms and a missense mutation. Blood. 2006; 107(1) 118-125
- 118 Bongers T N, De Maat M P, Dippel D W, Uitterlinden A G, Leebeek F W. Absence of Pro475Ser polymorphism in ADAMTS-13 in Caucasians. J Thromb Haemost. 2005; 3(4) 805
- 119 Ruan C, Dai L, Su J, Wang Z, Ruan C. The frequency of P475S polymorphism in von Willebrand factor-cleaving protease in the Chinese population and its relevance to arterial thrombotic disorders. Thromb Haemost. 2004; 91(6) 1257-1258
- 120 Terrell D R, Williams L A, Vesely S K, Lämmle B, Hovinga J A, George J N. The incidence of thrombotic thrombocytopenic purpura-hemolytic uremic syndrome: all patients, idiopathic patients, and patients with severe ADAMTS-13 deficiency. J Thromb Haemost. 2005; 3(7) 1432-1436
- 121 Egerman R S, Witlin A G, Friedman S A, Sibai B M. Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome in pregnancy: review of 11 cases. Am J Obstet Gynecol. 1996; 175(4 Pt 1) 950-956
- 122 McCrae K R, Cines D B. Thrombotic microangiopathy during pregnancy. Semin Hematol. 1997; 34(2) 148-158
- 123 Gerth J, Schleussner E, Kentouche K, Busch M, Seifert M, Wolf G. Pregnancy-associated thrombotic thrombocytopenic purpura. Thromb Haemost. 2009; 101(2) 248-251
- 124 Rieger M, Mannucci P M, Kremer Hovinga J A et al.. ADAMTS13 autoantibodies in patients with thrombotic microangiopathies and other immunomediated diseases. Blood. 2005; 106(4) 1262-1267
- 125 Austin S K, Starke R D, Lawrie A S, Cohen H, Machin S J, Mackie I J. The VWF/ADAMTS13 axis in the antiphospholipid syndrome: ADAMTS13 antibodies and ADAMTS13 dysfunction. Br J Haematol. 2008; 141(4) 536-544
- 126 Matsuyama T, Kuwana M, Matsumoto M, Isonishi A, Inokuma S, Fujimura Y. Heterogeneous pathogenic processes of thrombotic microangiopathies in patients with connective tissue diseases. Thromb Haemost. 2009; 102(2) 371-378
- 127 Shimizu M, Nomura S, Ishii K et al.. The significance of ADAMTS13 in a patient with thrombotic thrombocytopenic purpura complicated autoimmune hepatitis. Thromb Haemost. 2009; 101(3) 599-600
- 128 Kiki I, Gundogdu M, Albayrak B, Bilgiç Y. Thrombotic thrombocytopenic purpura associated with Brucella infection. Am J Med Sci. 2008; 335(3) 230-232
- 129 Rossi F C, Angerami R N, de Paula E V et al.. A novel association of acquired ADAMTS13 inhibitor and acute dengue virus infection. Transfusion. 2009; , September 24 (Epub ahead of print)
- 130 Yagita M, Uemura M, Nakamura T, Kunitomi A, Matsumoto M, Fujimura Y. Development of ADAMTS13 inhibitor in a patient with hepatitis C virus-related liver cirrhosis causes thrombotic thrombocytopenic purpura. J Hepatol. 2005; 42(3) 420-421
- 131 Uemura M, Fujimura Y, Matsumoto M et al.. Comprehensive analysis of ADAMTS13 in patients with liver cirrhosis. Thromb Haemost. 2008; 99(6) 1019-1029
- 132 Bennett C L, Connors J M, Carwile J M et al.. Thrombotic thrombocytopenic purpura associated with clopidogrel. N Engl J Med. 2000; 342(24) 1773-1777
- 133 Bennett C L, Kim B, Zakarija A SERF-TTP Research Group et al. Two mechanistic pathways for thienopyridine-associated thrombotic thrombocytopenic purpura: a report from the SERF-TTP Research Group and the RADAR Project. J Am Coll Cardiol. 2007; 50(12) 1138-1143
- 134 Zakarija A, Kwaan H C, Moake J L et al.. Ticlopidine- and clopidogrel-associated thrombotic thrombocytopenic purpura (TTP): review of clinical, laboratory, epidemiological, and pharmacovigilance findings (1989–2008). Kidney Int Suppl. 2009; 112 S20-S24
- 135 Vesely S K, George J N, Lämmle B et al.. ADAMTS13 activity in thrombotic thrombocytopenic purpura-hemolytic uremic syndrome: relation to presenting features and clinical outcomes in a prospective cohort of 142 patients. Blood. 2003; 102(1) 60-68
- 136 Shelat S G, Smith P, Ai J, Zheng X L. Inhibitory autoantibodies against ADAMTS-13 in patients with thrombotic thrombocytopenic purpura bind ADAMTS-13 protease and may accelerate its clearance in vivo. J Thromb Haemost. 2006; 4(8) 1707-1717
- 137 Shelat S G, Ai J, Zheng X L. Molecular biology of ADAMTS13 and diagnostic utility of ADAMTS13 proteolytic activity and inhibitor assays. Semin Thromb Hemost. 2005; 31(6) 659-672
- 138 Ferrari S, Mudde G C, Rieger M, Veyradier A, Kremer Hovinga J A, Scheiflinger F. IgG subclass distribution of anti-ADAMTS13 antibodies in patients with acquired thrombotic thrombocytopenic purpura. J Thromb Haemost. 2009; 7(10) 1703-1710
- 139 Klaus C, Plaimauer B, Studt J D et al.. Epitope mapping of ADAMTS13 autoantibodies in acquired thrombotic thrombocytopenic purpura. Blood. 2004; 103(12) 4514-4519
- 140 Luken B M, Kaijen P H, Turenhout E A et al.. Multiple B-cell clones producing antibodies directed to the spacer and disintegrin/thrombospondin type-1 repeat 1 (TSP1) of ADAMTS13 in a patient with acquired thrombotic thrombocytopenic purpura. J Thromb Haemost. 2006; 4(11) 2355-2364
- 141 Luken B M, Turenhout E A, Kaijen P H et al.. Amino acid regions 572-579 and 657-666 of the spacer domain of ADAMTS13 provide a common antigenic core required for binding of antibodies in patients with acquired TTP. Thromb Haemost. 2006; 96(3) 295-301
- 142 Moake J L, Byrnes J J. Thrombotic microangiopathies associated with drugs and bone marrow transplantation. Hematol Oncol Clin North Am. 1996; 10(2) 485-497
- 143 Elliott M A, Nichols Jr W L, Plumhoff E A et al.. Posttransplantation thrombotic thrombocytopenic purpura: a single-center experience and a contemporary review. Mayo Clin Proc. 2003; 78(4) 421-430
- 144 Oleksowicz L, Bhagwati N, DeLeon-Fernandez M. Deficient activity of von Willebrand’s factor-cleaving protease in patients with disseminated malignancies. Cancer Res. 1999; 59(9) 2244-2250
- 145 Mannucci P M, Karimi M, Mosalaei A, Canciani M T, Peyvandi F. Patients with localized and disseminated tumors have reduced but measurable levels of ADAMTS-13 (von Willebrand factor cleaving protease). Haematologica. 2003; 88(4) 454-458
- 146 Medina P J, Sipols J M, George J N. Drug-associated thrombotic thrombocytopenic purpura-hemolytic uremic syndrome. Curr Opin Hematol. 2001; 8(5) 286-293
- 147 Sugimoto T, Saigo K, Shin T et al.. Von Willebrand factor-cleaving protease activity remains at the intermediate level in thrombotic thrombocytopenic purpura. Acta Haematol. 2005; 113(3) 198-203
- 148 Zakarija A, Bennett C. Drug-induced thrombotic microangiopathy. Semin Thromb Hemost. 2005; 31(6) 681-690
- 149 Bernardo A, Ball C, Nolasco L, Moake J F, Dong J F. Effects of inflammatory cytokines on the release and cleavage of the endothelial cell-derived ultralarge von Willebrand factor multimers under flow. Blood. 2004; 104(1) 100-106
- 150 Crawley J T, Lane D A, Woodward M, Rumley A, Lowe G D. Evidence that high von Willebrand factor and low ADAMTS-13 levels independently increase the risk of a non-fatal heart attack. J Thromb Haemost. 2008; 6(4) 583-588
- 151 Fuchigami S, Kaikita K, Soejima K et al.. Changes in plasma von Willebrand factor-cleaving protease (ADAMTS13) levels in patients with unstable angina. Thromb Res. 2008; 122(5) 618-623
- 152 Bongers T N, de Bruijne E L, Dippel D W et al.. Lower levels of ADAMTS13 are associated with cardiovascular disease in young patients. Atherosclerosis. 2009; 207(1) 250-254
- 153 Gombos T, Makó V, Cervenak L et al.. Levels of von Willebrand factor antigen and von Willebrand factor cleaving protease (ADAMTS13) activity predict clinical events in chronic heart failure. Thromb Haemost. 2009; 102(3) 573-580
- 154 Bongers T N, de Maat M P, van Goor M L et al.. High von Willebrand factor levels increase the risk of first ischemic stroke: influence of ADAMTS13, inflammation, and genetic variability. Stroke. 2006; 37(11) 2672-2677
- 155 Vergouwen M D, Bakhtiari K, van Geloven N, Vermeulen M, Roos Y B, Meijers J C. Reduced ADAMTS13 activity in delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage. J Cereb Blood Flow Metab. 2009; 29(10) 1734-1741
- 156 Matsuyama T, Uemura M, Ishikawa M et al.. Increased von Willebrand factor over decreased ADAMTS13 activity may contribute to the development of liver disturbance and multiorgan failure in patients with alcoholic hepatitis. Alcohol Clin Exp Res. 2007; 31(1, suppl) S27-S35
- 157 Uemura M, Fujimura Y, Matsuyama T et al.. Potential role of ADAMTS13 in the progression of alcoholic hepatitis. Curr Drug Abuse Rev. 2008; 1(2) 188-196
- 158 Morioka C, Uemura M, Matsuyama T et al.. Plasma ADAMTS13 activity parallels the APACHE II score, reflecting an early prognostic indicator for patients with severe acute pancreatitis. Scand J Gastroenterol. 2008; 43(11) 1387-1396
- 159 de Mast Q, Groot E, Lenting P J et al.. Thrombocytopenia and release of activated von Willebrand Factor during early Plasmodium falciparum malaria. J Infect Dis. 2007; 196(4) 622-628
- 160 de Mast Q, Groot E, Asih P B de MQ et al. ADAMTS13 deficiency with elevated levels of ultra-large and active von Willebrand factor in P. falciparum and P. vivax malaria. Am J Trop Med Hyg. 2009; 80(3) 492-498
- 161 Larkin D, de Laat B, Jenkins P V et al.. Severe Plasmodium falciparum malaria is associated with circulating ultra-large von Willebrand multimers and ADAMTS13 inhibition. PLoS Pathog. 2009; 5(3) e1000349
- 162 Nguyen T C, Han Y Y, Kiss J E et al.. Intensive plasma exchange increases a disintegrin and metalloprotease with thrombospondin motifs-13 activity and reverses organ dysfunction in children with thrombocytopenia-associated multiple organ failure. Crit Care Med. 2008; 36(10) 2878-2887
- 163 Zhou Z, Han H, Cruz M A, López J A, Dong J F, Guchhait P. Haemoglobin blocks von Willebrand factor proteolysis by ADAMTS-13: a mechanism associated with sickle cell disease. Thromb Haemost. 2009; 101(6) 1070-1077
- 164 Chauhan A K, Motto D G, Lamb C B et al.. Systemic antithrombotic effects of ADAMTS13. J Exp Med. 2006; 203(3) 767-776
- 165 Zhao B Q, Chauhan A K, Canault M et al.. von Willebrand factor-cleaving protease ADAMTS13 reduces ischemic brain injury in experimental stroke. Blood. 2009; 114(15) 3329-3334
Zhou ZhouM.D. Ph.D.
Thrombosis Division, Section of Cardiovascular Research, Department of Medicine
Baylor College of Medicine, Houston, TX
eMail: zz144319@bcm.tmc.edu