Education

Biography

Han-Mou Tsai M.D. is a hematologist specializing in thrombosis and hemostasis. His research interest has focused on translational investigation, pioneering the discovery of ADAMTS13 and its deficiency in thrombotic thrombocytopenic purpura. He was formerly Professor of Medicine at Albert Einstein College of Medicine, Bronx, NY; and Professor of Medicine and Pathology and M. Elaine Eyster MD Professor of Hematology at Pennsylvania State University Hershey Medical Center, Hershey, PA. He currently practices as a private consultant.

Research Interest

His Research Interest includes translational investigation

Professional Activities:

Awards and honors:

Research:

Proteolysis and homeostasis of von Willebrand factor. The work has led to the discovery and cloning of ADAMTS13 and of its deficiency, due to autoimmune inhibitors or genetic mutations, in TTP.

Clinical practice:

Publications

Peer-Reviewed Original Communications

1. Tsai HM, Nagel RL, Hatcher VB, Sussman, II. Endothelial cell-derived high molecular weight von Willebrand factor is converted into the plasma multimer pattern by granulocyte proteases. BiochemBiophys Res Commun 1989;158:980-985
2. Tsai HM, Nagel RL, Hatcher VB, Sussman II. Multimeric composition of endothelial cell-derived von Willebrand factor. Blood 1989;73:2074-206
3. Tsai HM, Sussman II, Nagel RL, Kaul DK. Desmopressin induces adhesion of normal human erythrocytes to the endothelial surfaces of a perfused microvascular preparation. Blood 1990;75:261-265
4. Tsai HM, Nagel RL, Sussman II. Subunit composition of plasma von Willebrand factor multimers. Evidence for a non-proteolytic mechanism resulting in apparent increase in proteolytic fragments. Thromb Res 1991;63:179-88 
5. Tsai HM, Nagel RL, Hatcher VB, Seaton AC, Sussman II. The high molecular weight form of endothelial cell von Willebrand factor is released by the regulated pathway. Brit J Haematol 1991;79:239-245
6. Kaul DK, Nagel RL, Chen D, Tsai HM. Sickle erythrocyte-endothelial interaction in microcirculation: the role of von Willebrand factor and implications for vasoocclusion. Blood 1993;81:2429-2438
7. Tsai HM, Sussman II, Nagel RL. Shear stress promotes proteolysis of von Willebrand factor. Blood 1994;83:2171-2179
8. Kaul DK, Tsai HM, Nagel RL, Chen D. Platelet-activating factor enhances adhesion of sickle erythrocytes to the vascular endothelium: The role of vascular integrin avb3 and von Willebrand factor, in Beuzard Y, Lubin B, Rosa J (eds): Sickle Cell Disease and Thalassemias: New Trends in Therapy (Proceedings of INSERM Symposium, Paris, September 19-22), France, Colloque INSERM/John LibbeyEurotext, 1995, p497
9. Tsai HM. Physiologic cleavage of von Willebrand factor by a plasma protease is dependent on its conformation and requires calcium ion. Blood 1996;87:4235-4244
10. Tsai HM, Sussman II, Ginsburg D, Lankhof H, Sixma JJ, Nagel RL. Proteolytic cleavage of recombinant type 2A von Willebrand factor mutants R834W and R834Q: Inhibition by doxycyline and by monoclonal antibody VP-1. Blood 1997;89:1954-1962
11. Lankhof H, Damas C, Schiphorst M, Ljsseldijk W, Madelon B, Furlan M, Tsai HM, de Groot PG, Sixma JJ. von Willebrand factor without the A2 domain is resistant to proteolysis. Thrombosis Haemostasis 1997;77:1008-1013
12. Tsai HM, Lian E. C.-Y. Antibodies to von Willebrand factor-cleaving protease in acute thrombotic thrombocytopenic purpura. N Engl J Med 1998;339:1585-1594
13. Kaul DK, Tsai HM, Liu XD, Nakada MT, Nagel RL, Coller BS. Monoclonal antibodies to αVβ3 (7E3 and LM609) inhibit sickle red cell-endothelium interactions induced by platelet-activating factor. Blood 2000;95:368-374
14. Tsai HM, Rice L, Sarode R, Chow TW, Moake JL. Antibody inhibitors to von Willebrand factor metalloproteinase and increased von Willebrand factor-platelet binding in ticlopidine-associated thrombotic thrombocytopenic purpura. Ann Intern Med 2000;132:794-799
15. Bennett CL, Connors JM, Carwile JM, Moake JL, Bell WR, McCarthy LJ, Sarode R, Tarantola S. Hatfield AJ, Michalets EL, Feldman MD, Davidson CJ, Tsai HM. Thrombotic thrombocytopenic purpura associated with clopidogrel. N Engl J Med 2000;342:1773-1777
16. Sarode R, Goldstein J, Sussman II, Nagel RL, Tsai HM. Role of A and B blood group antigens in the expression of von Willebrand factor adhesive activity. Brit J Haematol 2000;109: 857-864
17. Tsai HM. High titers of inhibitors of von Willebrand factor-cleaving meatlloproteinase in a fatal case of acute thrombotic thrombocytopenic purpura. Am J Hematol 2000;65:251-255
18. O'Brien JR, Tsai HM, Etherington MD. Defective von willebrand factor activity detected by the filterometer in three clinical conditions. Platelets 2000;11:388-394
19. Raghavachari M, Tsai H, Kottke-Marchant K, Marchant RE. Surface dependent structures of von Willebrand factor observed by AFM under aqueous conditions. Colloids Surf B Biointerfaces 2000;19:315-324
    
20. Tsai HM, Chandler WL, Sarode R, Hoffman R, Jelacic S, Habeeb RL, Watkins SL, Wong CS, Williams GD, Tarr PI. von Willebrand factor and von Willebrand factor-cleaving metalloprotease activity in Escherichia coli O157:H7-associated hemolytic uremic. Pediatric Res 2001;49:653-659
21. O’Brien JR, Tsai HM, Etherington MD. A comparison of von Willebrand factor antigen with platelet activity in vitro in normal and venous occlusion blood. Platelets 2001;12:27-33
22. Tsai HM, Li A, Rock G. Inhibitors of von Willebrand factor-cleaving protease in thrombotic thrombocytopenic purpura. Clin Lab 2001;47:387-392
23. Arai S, Allan C, Streiff M, Hutchins GM, Vogelsang GB, Tsai HM. Von Willebrand factor-cleaving protease activity and proteolysis of von Willebrand factor in bone marrow transplant-associated thrombotic microangiopathy. Hematology J 2001;2: 292-299
24. Buhler L, Goepfert C, Kitamura H, Basker M, Gojo S, Alwayn IP, Chang Q, Down JD, Tsai H, Wise R, Sachs DH, Cooper DK, Robson SC, Sackstein R. Porcine hematopoietic cell xenotransplantation in nonhuman primates is complicated by thrombotic microangiopathy. Bone Marrow Transplant. 2001;27:1227-1236
25. Levy GG, Nichols WC, Lian EC,  Foroud T, McClintick J, McGee B, Yang A, Siemieniak D, Stark KR, Gruppo R, Sarode R, Shurin S, Chandrasekaran V, Stabler SP, Sabio H, Bouhassira EE, Upshaw J, Ginsburg D, Tsai HM. Mutations in a novel member of the ADAMTS gene family cause thrombotic thrombocytopenic purpura. Nature 2001;413:488-494
26. Robson WL, Tsai HM. Thrombotic thrombocytopenic purpura attributable to von Willebrand factor-cleaving protease inhibitor in an 8-year-old boy. Pediatrics 2002;109:322-325
27. Tsai HM, Tarr PI. Rebuttal to von Willebrand factor-cleaving protease in childhood diarrhea-associated hemolytic uremic syndrome. ThrombHaemost 2002;87:548-550
28. Gutterman LA, Kloster B, Tsai HM. Rituximab therapy for refractory thrombotic thrombocytopenic purpura. Blood Cells Mol Dis 2002;28:385-391
29. Cosmai EM, Puzis L, Tsai HM, Lian EC. Thrombocytopenic purpura and cardiomyopathy in pregnancy reversed by combined plasma exchange and infusion. Eur J Haematol. 2002;68:239-242
30. Raff JP, Dobson C, Tsai HM. Transfusion of polymerized human hemoglobin solution in a patient with severe sickle cell anemia. Lancet 2002;360:464-465
31. Tsai HM. Deficiency of ADAMTS13 and thrombotic thrombocytopenic purpura. Transfusion 2002;42:1523-1524. (Letter)
    
32. Pham PT, Danovitch GM, Wilkinson AH, Gritsch HA, Pham PC, Eric TM, Kendrick E, Charles LR, Tsai HM. Inhibitors of ADAMTS13: a potential factor in the cause of thrombotic microangiopathy in a renal allograft recipient. Transplantation 2002;74:1077-1080
33. Tsai HM. ADAMTS13 deficiency and TTP. Blood 2002;100:3839 (Letter)
34. Morgensztern DM, Kharfan-Dabaja MA, Tsai HM, Lian ECY. Warm-antibody autoimmune hemolytic anemia devekoping after thrombotic thrombocytopenic purpura. ActaHaematol 2002;108:154-156.
35. Tarr PI, Tsai HM, Chandler W. Thrombotic microangiopathies. N Engl J M 2002;347:2171-2172 (Letter)
36. Jubinsky P, Moraille R, Tsai HM. Thrombotic thrombocytopenic purpura in a newborn. J Perinatology 2003;23:85-87
37. Tsai HM, Sarode R, Downes KA. Ultra large von Willebrand factor multimers and normal ADAMTS13 activity in the umbilical cord blood. Thromb Res 2003;109:121-125
38. Tsai HM, Shulman K. Rituximab induces remission of cerebral ischemia caused by thrombotic thrombocytopenic purpura. Eur J Haematol 2003;70:183-185
39. Forman RB, Benkel SA, Novik Y, Tsai HM. Presence of ADAMTS13 activity in a patient with metastatic cancer and thrombotic microangiopathy. ActaHaematol. 2003;109:150-152
40. Savaşan S, Lee SK, GinsburgD, Tsai HM. ADAMTS13 gene mutation in congenital thrombotic thrombocytopenic purpura with previously reported normal VWF cleaving protease activity. Blood 2003;101:4449-4451
41. Zhou W, Tsai HM. An Enzyme Immunoassay of ADAMTS13 distinguishes patients with thrombotic thrombocytopenic purpura from normal individuals and carriers of ADAMTS13 mutations. ThrombHaemost 2004;91:806-811
42. Yomtovian R, Niklinski W, Silver B, Sarode R, Tsai HM.  Rituximab for chronic recurring thrombotic thrombocytopenic purpura: a case report and review of the literature. Brit J Haematol 2004;124:787-795. PMID: 15009067
43. DownesKA, YomtovianR, TsaiHM, SilverB, RutherfordC, Sarode R.  Relapsed Thrombotic Thrombocytopenic Purpura Presenting as an Acute Cerebrovascular Accident. J ClinApher 2004; 19:86-89.
44. Schiff DE, Roberts WD, Willert J, Tsai HM. Thrombocytopenia and severe hyperbilirubinemia in the neonatal period secondary to congenital thrombotic thrombocytopenic purpura and ADAMTS13 deficiency. J Ped HematolOncol 2004;26:535-538.
45. Tsai HM. Type 2 A (group II) von Willebrand disease mutations increase the susceptibility of VWF to ADAMTS-13. J ThrombHaemost 2004;2:2057.PMID: 15550049 (Letter)
46. Zhou W, Inada M, Lee TP, Benten D, Lyubsky S, Bouhassira EE, Gupta S, Tsai HM.  ADAMTS13 is expressed in hepatic stellate cells. Lab Invest 2005; 85:780-788.PMID: 15806136
47. Motto DG, Chauhan AK, Zhu G, Homeister J, Lamb CB, Desch KC, Zhang W, Tsai HM, Wagner DD, Ginsburg D.  Shigatoxin triggers thrombotic thrombocytopenic purpura in genetically susceptible ADAMTS13-deficient mice. J Clin Invest 2005;115:2752-2761.PMID: 16200209 PMCID: PMC1240119
48. Zhou W, Dong L, Ginsburg D, Bouhassira EE, Tsai HM. Enzymatically-active ADAMTS13 variants are not inhibited by anti-ADAMTS13 autoantibodies – a novel therapeutic strategy? J BiolChem 2005;280:39934-41. PMID: 16203734PMCID: PMC2582217
49. TsaiHM, RaoufiM, ZhouW, GuintoE, GrafosN, RanzurmalN, GreenfieldRS, Rand JH. ADAMTS13-Binding IgG is present in patients with thrombotic thrombocytopenic purpura. ThrombHaemost 2006;95:886-892.PMCID: PMC2603189
50. Hirata S, Okamoto H, Ohta S, Kobashigawa T, Uesato M, Kawaguchi Y, Tateishi M, Hara M, Kamatani N, Tsai HM. Deficient activity of von Willebrand factor-cleaving protease in thrombotic thrombocytopenic purpura in the setting of adult-onset Still's disease. Rheumatology (Oxford) 2006; 45:1046-1047.PMID: 16720635
51. Manea M, Kristoffersson A, Tsai HM, Zhou W, Winqvist I, Oldaeus G, Billstrom R, Bjork P, Holmberg L, Karpman D. ADAMTS13 phenotype in plasma from normal individuals and patients with thrombotic thrombocytopenic purpura. Eur J Pediatr 2006;166:249-257.PMID: 17187257 PMCID: PMC1820762
52. Zhou W, Bouhassira EE, Tsai HM. An IAP retrotransposon in the ADAMTS13 gene creates ADAMTS13 variant proteins that are less effective in cleaving von Willebrand factor multimers. Blood 2007;110:886-893.PMID: 17426255 PMCID: PMC1924774
53. Dong L, Chandrasekaran V, Zhou W, Tsai HM. Evolution of ADAMTS13 antibodies in a patient with fatal thrombotic thrombocytopenic purpura. Am J Hematol2008;83:815-817.PMID: 18661493 PMCID: PMC2574606
54. Zhou W, Tsai HM. N-Glycans of ADAMTS13 modulate its secretion and von Willebrand factor cleaving activity. Blood2009;113:929-935.PMID: 18981290 PMCID: PMC2630278
55. Larrea L, Calabuig M, Roldan V, Rivera J, Tsai HM, Vicente V, Roig R. The Influence of riboflavin photochemistry on plasma coagulation factors. TransfusApherSc2009;41:199-204.PMID: 19782644 PMCID: PMC3158998
56. Tarr PI, Sadler JE, Chandler WL, George JN, Tsai HM. Should all adult patients with diarrhoea-associated HUS receive plasma exchange? Lancet 2012;11:379:516. PMID: 22325653
57. Chapin J, EylerS, Smith R, Tsai HM, Laurence J. Complement factor H mutations are present in ADAMTS13 deficient ticlopidine-associated TTP. Blood 2013;121:4012-4013. PMID: 23660864
58. Tsai E, Chapin J, Laurence J, Tsai HM. Use of eculizumab in the treatment of a case of refractory, ADAMTS13 deficient thrombotic thrombocytopenic purpura: additional data and clinical follow-up. Br J Haematol  2013; 162:558-9. PMID: 23692124
59. Tsai HM, Kuo E. Eculizumab therapy leads to rapid resolution of thrombocytopenia in atypical hemolytic uremic syndrome. AdvHematol2014;2014:295323.http://dx.doi.org/10.1155/2014/295323
60. Tsai HM. Does anticomplement therapy have a role in the management of malignant hypertension?J Clin Hypertension 2015.http://dx.doi.org/10.1111/jch.12664PMID: 26359936