Open Access Open Access  Restricted Access Subscription or Fee Access

Thrombotic thrombocytopenic purpura: A Narrative Review of Diagnosis and Treatment by drugs and novel agents.

Asad Jamal Ansari, Shweta S, Mohammad Monawwar, Nishat Fatima

Abstract


Thrombotic thrombocytopenic purpura (TTP) is an infrequent but fatal disease, is primarily caused by autoantibodies against the von Willebrand factor (VWF) cleaving metalloprotease ADAMTS13. Overall, severe deficiency of plasma ADAMTS13 action (< 10 IU dL-1) with or without noticeable inhibitory autoantibodies counter to ADAMTS13 supports the diagnosis of TTP. The International Working Group for TTP released a consensus statement on the standardization of terminology in these disorders which we use in this publication. Plasma exchange and corticosteroids remain to be the support of treatment, though, repurposed drugs and novel agents are evolving as effectual treatment options. In this review, new therapeutic expansions in immune mediated thrombotic thrombocytopenic purpura (TTP) counting bortezomib, N-acetylcysteine, caplacizumab, rituximab, and recombinant ADAMTS13, amongst others, are abridged.


Keywords


ADAMTS13, bortezomib, caplacizumab, N-acetylcysteine, rituximab, Thrombotic thrombocytopenic purpura

Full Text:

PDF

References


Scully M, Hunt BJ, Benjamin S, Liesner R, Rose P, Peyvandi F, Cheung B, Machin SJ. British Committee for Standards in Haematology. Guidelines on the diagnosis and management of thrombotic thrombocytopenic purpura and other thrombotic microangiopathies. Br J Haematol. 2012;158(3):323-35.

Shatzel JJ, Taylor JA. Syndromes of thrombotic microangiopathy. Medical Clinics. 2017 Mar 1;101(2):395-415.

Scully M, Cataland S, Coppo P, de la Rubia J, Friedman KD, Kremer Hovinga J, Lammle B, Matsumoto M, Pavenski K, Sadler E, Sarode R. International Working Group for Thrombotic Thrombocytopenic Purpura. Consensus on the standardization of terminology in thrombotic thrombocytopenic purpura and related thrombotic microangiopathies. J Thromb Haemost. 2017;15(2):312-22.

Page EE, Kremer Hovinga JA, Terrell DR, Vesely SK, George JN. Thrombotic thrombocytopenic purpura: diagnostic criteria, clinical features, and long-term outcomes from 1995 through 2015. Blood advances. 2017 Apr 11;1(10):590-600.

Sarode R, Gottschall JL, Aster RH, McFarland JG. Thrombotic thrombocytopenic purpura: early and late responders. American journal of hematology. 1997 Feb;54(2):102-7.

Sayani FA, Abrams CS. How I treat refractory thrombotic thrombocytopenic purpura. Blood. 2015 Jun 18;125(25):3860-7.

Bendapudi PK, Li A, Hamdan A, Uhl L, Kaufman R, Stowell C, Dzik W, Makar RS. Impact of severe ADAMTS13 deficiency on clinical presentation and outcomes in patients with thrombotic microangiopathies: the experience of the Harvard TMA Research Collaborative. British journal of haematology. 2015 Dec;171(5):836-44.

Ayanambakkam A, Kremer Hovinga JA, Vesely SK, George JN. Diagnosis of thrombotic thrombocytopenic purpura among patients with ADAMTS13 Activity 10%‐20%. American Journal of Hematology. 2017 Nov;92(11):E644-6.

Chiasakul T, Cuker A. Clinical and laboratory diagnosis of TTP: an integrated approach. Hematology. 2018 Nov 30;2018(1):530-8.

Mackie I, Langley K, Chitolie A, Liesner R, Scully M, Machin S, Peyvandi F. Discrepancies between ADAMTS13 activity assays in patients with thrombotic microangiopathies. Thrombosis and haemostasis. 2013;109(03):488-96.

Mancini I, Valsecchi C, Lotta LA, Deforche L, Pontiggia S, Bajetta M, Palla R, Vanhoorelbeke K, Peyvandi F. FRETS-VWF73 rather than CBA assay reflects ADAMTS13 proteolytic activity in acquired thrombotic thrombocytopenic purpura patients. Thrombosis and haemostasis. 2014 Aug;112(08):297-303.

Binder NB, Griffiths M, Vetr H. A rapid and simple assay for the determination of Adamts-13 activity. Blood.2016;128 (22): 1399.

Joly BS, Coppo P, Veyradier A. Thrombotic thrombocytopenic purpura. Blood. 2017 May 25;129(21):2836-46.

Moschcowitz E. Hyaline thrombosis of the terminal arterioles and capillaries: a hitherto undescribed disease. InProc. NY Pathol Soc. 1924;Vol. 24;pp. 21-24).

AMOROSI EL, ULTMANN JE. Thrombotic thrombocytopenic purpura: report of 16 cases and review of the literature. Medicine. 1966 Mar 1;45(2):139-60.

Zheng XL, Kaufman RM, Goodnough LT, Sadler JE. Effect of plasma exchange on plasma ADAMTS13 metalloprotease activity, inhibitor level, and clinical outcome in patients with idiopathic and nonidiopathic thrombotic thrombocytopenic purpura. Blood. 2004 Jun 1;103(11):4043-9.

Bell WR, Braine HG, Ness PM, Kickler TS. Improved survival in thrombotic thrombocytopenic purpura–hemolytic uremic syndrome: clinical experience in 108 patients. New England Journal of Medicine. 1991 Aug 8;325(6):398-403.

Moake JL, Rudy CK, Troll JH, Weinstein MJ, Colannino NM, Azocar J, Seder RH, Hong SL, Deykin D. Unusually large plasma factor VIII: von Willebrand factor multimers in chronic relapsing thrombotic thrombocytopenic purpura. New England Journal of Medicine. 1982 Dec 2;307(23):1432-5.

Alwan F, Vendramin C, Vanhoorelbeke K, Langley K, McDonald V, Austin S, Clark A, Lester W, Gooding R, Biss T, Dutt T. Presenting ADAMTS13 antibody and antigen levels predict prognosis in immune-mediated thrombotic thrombocytopenic purpura. Blood, The Journal of the American Society of Hematology. 2017 Jul 27;130(4):466-71.

Matsumoto M, Bennett CL, Isonishi A, Qureshi Z, Hori Y, Hayakawa M, Yoshida Y, Yagi H, Fujimura Y. Acquired idiopathic ADAMTS13 activity deficient thrombotic thrombocytopenic purpura in a population from Japan. PLoS One. 2012 Mar 12;7(3):e33029.

Scully M, Yarranton H, Liesner R, Cavenagh J, Hunt B, Benjamin S, Bevan D, Mackie I, Machin S. Regional UK TTP registry: correlation with laboratory ADAMTS 13 analysis and clinical features. British journal of haematology. 2008 Sep;142(5):819-26.

Mariotte E, Azoulay E, Galicier L, Rondeau E, Zouiti F, Boisseau P, Poullin P, de Maistre E, Provôt F, Delmas Y, Perez P. Epidemiology and pathophysiology of adulthood-onset thrombotic microangiopathy with severe ADAMTS13 deficiency (thrombotic thrombocytopenic purpura): a cross-sectional analysis of the French national registry for thrombotic microangiopathy. The Lancet Haematology. 2016 May 1;3(5):e237-45.

Crawley JT, de Groot R, Xiang Y, Luken BM, Lane DA. Unraveling the scissile bond: how ADAMTS13 recognizes and cleaves von Willebrand factor. Blood. 2011 Sep 22;118(12):3212-21.

Joly BS, Coppo P, Veyradier A. An update on pathogenesis and diagnosis of thrombotic thrombocytopenic purpura. Expert review of hematology. 2019 Jun 3;12(6):383-95.

Moake JL, Rudy CK, Troll JH, Weinstein MJ, Colannino NM, Azocar J, Seder RH, Hong SL, Deykin D. Unusually large plasma factor VIII: von Willebrand factor multimers in chronic relapsing thrombotic thrombocytopenic purpura. New England Journal of Medicine. 1982 Dec 2;307(23):1432-5.

Levy GG, Nichols WC, Lian EC, Foroud T, McClintick JN, McGee BM, Yang AY, Siemieniak DR, Stark KR, Gruppo R, Sarode R. Mutations in a member of the ADAMTS gene family cause thrombotic thrombocytopenic purpura. Nature. 2001 Oct;413(6855):488-94.

Dent JA, Berkowitz SD. Ware J, Kasper CK, Ruggeri ZM: Identification of a cleavage site directing the immunochemical detection of molecular abnormalities in type IIA von Willebrand factor. Proc Natl Acad Sci USA. 1990;87:6306.

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, The Journal of the American Society of Hematology. 2001 Sep 15;98(6):1662-6.

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. Thrombosis and haemostasis. 1999;81(01):8-13.

Zheng XL. Structure–function and regulation of ADAMTS‐13 protease. Journal of Thrombosis and Haemostasis. 2013 Jun;11:11-23.

Tsai HM, Lian EC. Antibodies to von Willebrand factor–cleaving protease in acute thrombotic thrombocytopenic purpura. New England Journal of Medicine. 1998 Nov 26;339(22):1585-94.

Roose E, Schelpe AS, Joly BS, Peetermans M, Verhamme P, Voorberg J, Greinacher A, Deckmyn H, De Meyer SF, Coppo P, Veyradier A. An open conformation of ADAMTS‐13 is a hallmark of acute acquired thrombotic thrombocytopenic purpura. Journal of Thrombosis and Haemostasis. 2018 Feb;16(2):378-88.

Brazelton J, Oster RA, McCleskey B, Fuller J, Adamski J, Marques MB. Increased troponin I is associated with fatal outcome in acquired thrombotic thrombocytopenic purpura. Journal of clinical apheresis. 2017 Oct;32(5):311-8.

Zafrani L, Mariotte E, Darmon M, Canet E, Merceron S, Boutboul D, Veyradier A, Galicier L, Azoulay E. Acute renal failure is prevalent in patients with thrombotic thrombocytopenic purpura associated with low plasma ADAMTS 13 activity. Journal of Thrombosis and Haemostasis. 2015 Mar;13(3):380-9.

Coppo P, Schwarzinger M, Buffet M, Wynckel A, Clabault K, Presne C, Poullin P, Malot S, Vanhille P, Azoulay E, Galicier L. Predictive features of severe acquired ADAMTS13 deficiency in idiopathic thrombotic microangiopathies: the French TMA reference center experience. PloS one. 2010 Apr 23;5(4):e10208.

Bendapudi PK, Hurwitz S, Fry A, Marques MB, Waldo SW, Li A, Sun L, Upadhyay V, Hamdan A, Brunner AM, Gansner JM. Derivation and external validation of the PLASMIC score for rapid assessment of adults with thrombotic microangiopathies: a cohort study. The Lancet Haematology. 2017 Apr 1;4(4):e157-64.

Zheng XL, Kaufman RM, Goodnough LT, Sadler JE. Effect of plasma exchange on plasma ADAMTS13 metalloprotease activity, inhibitor level, and clinical outcome in patients with idiopathic and nonidiopathic thrombotic thrombocytopenic purpura. Blood. 2004 Jun 1;103(11):4043-9.

Rock GA, Shumak KH, Buskard NA. Blan chette VS, Kelton JG, Nair RC, Spasoff RA, The Canadian Apheresis Study Group: Com parison of Plasma Exchange with Plasma Infusion in The Treatment of Thombotic Thrombocytopenic Purpura. N Engl J Med. 1991;325:393-7.

Zini G, d’Onofrio G, Briggs C, Erber W, Jou JM, Lee SH, McFadden S, Vives‐Corrons JL, Yutaka N, Lesesve JF. ICSH recommendations for identification, diagnostic value, and quantitation of schistocytes. International journal of laboratory hematology. 2012 Apr;34(2):107-16.

Ruutu T, Barosi G, Benjamin RJ, Clark RE, George JN, Gratwohl A, Holler E, Iacobelli M, Kentouche K, Lämmle B, Moake JL. Diagnostic criteria for hematopoietic stem cell transplant-associated microangiopathy: results of a consensus process by an International Working Group. haematologica. 2007 Jan 1;92(1):95-100.

Egan JA, Hay SN, Brecher ME. Frequency and significance of schistocytes in TTP/HUS patients at the discontinuation of plasma exchange therapy. Journal of Clinical Apheresis: The Official Journal of the American Society for Apheresis. 2004;19(4):165-7.

Furlan M, Robles R, Galbusera M, Remuzzi G, Kyrle PA, Brenner B, Krause M, Scharrer I, Aumann V, Mittler U, Solenthaler M. Von Willebrand factor–cleaving protease in thrombotic thrombocytopenic purpura and the hemolytic–uremic syndrome. New England Journal of Medicine. 1998 Nov 26;339(22):1578-84.

Laurence J. Atypical hemolytic uremic syndrome (aHUS): making the diagnosis. Clin Adv Hematol Oncol. 2012 Oct 1;10(10 Suppl 17):1-2.

Barrows BD, Teruya J. Use of the ADAMTS13 activity assay improved the accuracy and efficiency of the diagnosis and treatment of suspected acquired thrombotic thrombocytopenic purpura. Archives of Pathology and Laboratory Medicine. 2014 Apr;138(4):546-9.

Kokame K, Nobe Y, Kokubo Y, Okayama A, Miyata T. FRETS‐VWF73, a first fluorogenic substrate for ADAMTS13 assay. British journal of haematology. 2005 Apr;129(1):93-100.

Mackie I, Langley K, Chitolie A, Liesner R, Scully M, Machin S, Peyvandi F. Discrepancies between ADAMTS13 activity assays in patients with thrombotic microangiopathies. Thrombosis and haemostasis. 2013;109(03):488-96.

Kato S, Matsumoto M, Matsuyama T, Isonishi A, Hiura H, Fujimura Y. Novel monoclonal antibody‐based enzyme immunoassay for determining plasma levels of ADAMTS13 activity. Transfusion. 2006 Aug;46(8):1444-52.

Jin M, Cataland S, Bissell M, Wu HM. A rapid test for the diagnosis of thrombotic thrombocytopenic purpura using surface enhanced laser desorption/ionization time‐of‐flight (SELDI‐TOF)‐mass spectrometry. Journal of Thrombosis and Haemostasis. 2006 Feb;4(2):333-8.

Knovich MA, Craver K, Matulis MD, Lawson H, Owen J. Simplified assay for VWF cleaving protease (ADAMTS13) activity and inhibitor in plasma. American journal of hematology. 2004 Jul;76(3):286-90.

Meyer SC, Sulzer I, Lammle B, Kremer Hovinga JA. Hyperbilirubinemia interferes with ADAMTS-13 activity measurement by FRETS-VWF73 assay: diagnostic relevance in patients suffering from acute thrombotic microangiopathies. Journal of thrombosis and haemostasis. 2007 Apr 1;5(4):866-7.

Muia J, Gao W, Haberichter SL, Dolatshahi L, Zhu J, Westfield LA, Covill SC, Friedman KD, Sadler JE. An optimized fluorogenic ADAMTS 13 assay with increased sensitivity for the investigation of patients with thrombotic thrombocytopenic purpura. Journal of Thrombosis and Haemostasis. 2013 Aug;11(8):1511-8.

Coppo P, Schwarzinger M, Buffet M, Wynckel A, Clabault K, Presne C, Poullin P, Malot S, Vanhille P, Azoulay E, Galicier L. Predictive features of severe acquired ADAMTS13 deficiency in idiopathic thrombotic microangiopathies: the French TMA reference center experience. PloS one. 2010 Apr 23;5(4):e10208.

Rock GA, Shumak KH, Buskard NA, Blanchette VS, Kelton JG, Nair RC, Spasoff RA, Canadian Apheresis Study Group*. Comparison of plasma exchange with plasma infusion in the treatment of thrombotic thrombocytopenic purpura. New England Journal of Medicine. 1991 Aug 8;325(6):393-7.

Ruggenenti P, Galbusera M, Cornejo RP, Bellavita P, Remuzzi G. Thrombotic thrombocytopenic purpura: Evidence that infusion rather than removal of plasma induces remission of the disease. American journal of kidney diseases. 1993 Mar 1;21(3):314-8.

McClain RS, Terrell DR, Vesely SK, George JN. Plasma exchange complications in patients treated for thrombotic thrombocytopenia purpura–hemolytic uremic syndrome: 2011 to 2014. Transfusion. 2014 Dec;54(12):3257-9.

Vendramin C, McGuckin S, Alwan F, Westwood JP, Thomas M, Scully M. A single‐center prospective study on the safety of plasma exchange procedures using a double‐viral‐inactivated and prion‐reduced solvent/detergent fresh‐frozen plasma as the replacement fluid in the treatment of thrombotic microangiopathy. Transfusion. 2017 Jan;57(1):131-6.

Scully M, McDonald V, Cavenagh J, Hunt BJ, Longair I, Cohen H, Machin SJ. A phase 2 study of the safety and efficacy of rituximab with plasma exchange in acute acquired thrombotic thrombocytopenic purpura. Blood, The Journal of the American Society of Hematology. 2011 Aug 18;118(7):1746-53.

Froissart A, Veyradier A, Hié M, Benhamou Y, Coppo P, French Reference Center for Thrombotic Microangiopathies. Rituximab in autoimmune thrombotic thrombocytopenic purpura: a success story. European journal of internal medicine. 2015 Nov 1;26(9):659-65.

Scully M, Cohen H, Cavenagh J, Benjamin S, Starke R, Killick S, Mackie I, Machin SJ. Remission in acute refractory and relapsing thrombotic thrombocytopenic purpura following rituximab is associated with a reduction in IgG antibodies to ADAMTS‐13. British journal of haematology. 2007 Feb;136(3):451-61.

Froissart A, Buffet M, Veyradier A, Poullin P, Provôt F, Malot S, Schwarzinger M, Galicier L, Vanhille P, Vernant JP, Bordessoule D. Efficacy and safety of first-line rituximab in severe, acquired thrombotic thrombocytopenic purpura with a suboptimal response to plasma exchange. Experience of the French Thrombotic Microangiopathies Reference Center. Critical care medicine. 2012 Jan 1;40(1):104-11.

Lim W, Vesely SK, George JN. The role of rituximab in the management of patients with acquired thrombotic thrombocytopenic purpura. Blood, The Journal of the American Society of Hematology. 2015 Mar 5;125(10):1526-31.

Westwood JP, Webster H, McGuckin S, McDonald V, Machin SJ, Scully M. Rituximab for thrombotic thrombocytopenic purpura: benefit of early administration during acute episodes and use of prophylaxis to prevent relapse. Journal of Thrombosis and Haemostasis. 2013 Mar;11(3):481-90.

Sun L, Mack J, Li A, Ryu J, Upadhyay VA, Uhl L, Kaufman RM, Stowell CP, Dzik WS, Makar RS, Bendapudi PK. Predictors of relapse and efficacy of rituximab in immune thrombotic thrombocytopenic purpura. Blood advances. 2019 May 14;3(9):1512-8.

Cataland SR, Kourlas PJ, Yang S, Geyer S, Witkoff L, Wu H, Masias C, George JN, Wu HM. Cyclosporine or steroids as an adjunct to plasma exchange in the treatment of immune-mediated thrombotic thrombocytopenic purpura. Blood Advances. 2017 Oct 24;1(23):2075-82.

Dervenoulas J, Tsirigotis P, Bollas G, Pappa V, Xiros N, Economopoulos T, Pappa M, Mellou S, Kostourou A, Papageorgiou E, Raptis SA. Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS): treatment outcome, relapses, prognostic factors. A single-center experience of 48 cases. Annals of hematology. 2000 Feb 1;79(2):66-72.

Bendapudi PK, Li A, Hamdan A, Fry AM, Uhl L, Marques M, Kaufman R, Stowell CP, Dzik WS, Makar RS. Derivation and prospective validation of a predictive score for the rapid diagnosis of thrombotic thrombocytopenic purpura: the plasmic score. Blood.2014;124 (21): 231.

Jake Shortt MB, Opat SS. ADAMTS13 antibody depletion by bortezomib in thrombotic thrombocytopenic purpura. The New England journal of medicine. 2013 Jan 3;368(1):90.

Sorvillo N, Pos W, van den Berg LM, Fijnheer R, Martinez-Pomares L, Geijtenbeek TB, Herczenik E, Voorberg J. The macrophage mannose receptor promotes uptake of ADAMTS13 by dendritic cells. Blood, The Journal of the American Society of Hematology. 2012 Apr 19;119(16):3828-35.

Subklewe M, Sebelin-Wulf K, Beier C, Lietz A, Mathas S, Dörken B, Pezzutto A. Dendritic cell maturation stage determines susceptibility to the proteasome inhibitor bortezomib. Human immunology. 2007 Mar 1;68(3):147-55.

Eskazan AE. Bortezomib therapy in patients with relapsed/refractory acquired thrombotic thrombocytopenic purpura. Annals of hematology. 2016 Nov 1;95(11):1751-6.

Chen J, Reheman A, Gushiken FC, Nolasco L, Fu X, Moake JL, Ni H, López JA. N-acetylcysteine reduces the size and activity of von Willebrand factor in human plasma and mice. The Journal of clinical investigation. 2011 Feb 1;121(2):593-603.

Tersteeg C, Roodt J, Van Rensburg WJ, Dekimpe C, Vandeputte N, Pareyn I, Vandenbulcke A, Plaimauer B, Lamprecht S, Deckmyn H, Lopez JA. N-acetylcysteine in preclinical mouse and baboon models of thrombotic thrombocytopenic purpura. Blood, The Journal of the American Society of Hematology. 2017 Feb 23;129(8):1030-8.

Li GW, Rambally S, Kamboj J, Reilly S, Moake JL, Udden MM, Mims MP. Treatment of refractory thrombotic thrombocytopenic purpura with N‐acetylcysteine: a case report. Transfusion. 2014 May;54(5):1221-4.

Cabanillas G, Popescu-Martinez A. N-acetylcysteine for relapsing thrombotic thrombocytopenic purpura: more evidence of a promising drug. American Journal of Therapeutics. 2016 Sep 1;23(5):e1277-9.

Shortt J, Opat SS, Wood EM. N-Acetylcysteine for thrombotic thrombocytopenic purpura: is a von Willebrand factor-inhibitory dose feasible in vivo?. Transfusion. 2014 Sep;54(9):2362.

Acedillo RR, Govind M, Kashgary A, Clark WF. Treatment of severe, refractory and rapidly evolving thrombotic thrombocytopenic purpura. Case Reports. 2016 Jun 9;2016:bcr2016215491.

Allanby KD, Huntsman RG, Sacker LS. Thrombotic microangiopathy: Recovery of a case after heparin and magnesium therapy. The Lancet. 1966 Jan 29;287(7431):237-9.

Dong JF, Cruz MA, Aboulfatova K, Martin C, Choi H, Bergeron AL, Martini SR, Kroll MH, Kent TA. Magnesium maintains endothelial integrity, up-regulates proteolysis of ultra-large von Willebrand factor, and reduces platelet aggregation under flow conditions. Thrombosis and haemostasis. 2008;99(03):586-93.

Ravn HB, Vissinger H, Kristensen SD, Husted SE. Magnesium inhibits platelet activity-an in vitro study. Thrombosis and haemostasis. 1996 Jan;75(01):088-93.

Shechter M, Merz CN, Rude RK, Labrador MJ, Meisel SR, Shah PK, Kaul S. Low intracellular magnesium levels promote platelet-dependent thrombosis in patients with coronary artery disease. American heart journal. 2000 Aug 1;140(2):212-8.

Nadler JL, Malayan S, Luong H, Shaw S, Natarajan RD, Rude RK. Intracellular free magnesium deficiency plays a key role in increased platelet reactivity in type II diabetes mellitus. Diabetes care. 1992 Jul 1;15(7):835-41.

Hovinga JK, Studt JD, Biasiutti FD, Solenthaler M, Alberio L, Zwicky C, Fontana S, Taleghani BM, Tobler A, Lämmle B. Splenectomy in relapsing and plasma-refractory acquired thrombotic thrombocytopenic purpura. haematologica. 2004 Jan 1;89(3):320-4.

Dubois L, Gray DK. Splenectomy: Does it still play a role in the management of thrombotic thrombocytopenic purpura?. Canadian Journal of Surgery. 2010 Oct;53(5):349.

Lombardi AM, Di Pasquale I, Businaro MA, Cortella I, Ferrari S, Fabris F, Vianello F. Relapsing thrombotic thrombocytopenic purpura with low ADAMTS13 antigen levels: An indication for splenectomy?. Hematology reports. 2019 Feb 19;11(1).

Ulrichts H, Silence K, Schoolmeester A, de Jaegere P, Rossenu S, Roodt J, Priem S, Lauwereys M, Casteels P, Van Bockstaele F, Verschueren K. Antithrombotic drug candidate ALX-0081 shows superior preclinical efficacy and safety compared with currently marketed antiplatelet drugs. Blood, The Journal of the American Society of Hematology. 2011 Jul 21;118(3):757-65.

Callewaert F, Roodt J, Ulrichts H, Stohr T, van Rensburg WJ, Lamprecht S, Rossenu S, Priem S, Willems W, Holz JB. Evaluation of efficacy and safety of the anti-VWF Nanobody ALX-0681 in a preclinical baboon model of acquired thrombotic thrombocytopenic purpura. Blood, The Journal of the American Society of Hematology. 2012 Oct 25;120(17):3603-10.

Peyvandi F, Scully M, Kremer Hovinga JA, Cataland S, Knöbl P, Wu H, Artoni A, Westwood JP, Mansouri Taleghani M, Jilma B, Callewaert F. Caplacizumab for acquired thrombotic thrombocytopenic purpura. New England Journal of Medicine. 2016 Feb 11;374(6):511-22.

Peyvandi F, Scully M, Kremer Hovinga JA, Knöbl P, Cataland S, De Beuf K, Callewaert F, De Winter H, Zeldin RK. Caplacizumab reduces the frequency of major thromboembolic events, exacerbations and death in patients with acquired thrombotic thrombocytopenic purpura. Journal of thrombosis and haemostasis. 2017 Jul;15(7):1448-52.

Zheng L, Mao Y, Abdelgawwad MS, Kocher NK, Li M, Dai X, Li B, Zheng XL. Therapeutic efficacy of the platelet glycoprotein Ib antagonist anfibatide in murine models of thrombotic thrombocytopenic purpura. Blood advances. 2016 Nov 29;1(1):75-83.

Turner N, Sartain S, Moake J. Ultralarge von Willebrand factor–induced platelet clumping and activation of the alternative complement pathway in thrombotic thrombocytopenic purpura and the hemolytic-uremic syndromes. Hematology/Oncology Clinics. 2015 Jun 1;29(3):509-24.

Tsai E, Zhou W, 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. British journal of haematology. 2013 Aug;162(4):558.

Plaimauer B, Kremer Hovinga JA, Juno C, Wolfsegger MJ, Skalicky S, Schmidt M, Grillberger L, Hasslacher M, Knöbl P, Ehrlich H, Scheiflinger F. Recombinant ADAMTS13 normalizes von Willebrand factor‐cleaving activity in plasma of acquired TTP patients by overriding inhibitory antibodies. journal of Thrombosis and Haemostasis. 2011 May;9(5):936-44.

Jian C, Xiao J, Gong L, Skipwith CG, Jin SY, Kwaan HC, Zheng XL. Gain-of-function ADAMTS13 variants that are resistant to autoantibodies against ADAMTS13 in patients with acquired thrombotic thrombocytopenic purpura. Blood, The Journal of the American Society of Hematology. 2012 Apr 19;119(16):3836-43.


Refbacks

  • There are currently no refbacks.


Copyright (c) 2020 Research & Reviews: Journal of Oncology and Hematology