Mechanism of Disease

Each aTTP episode can be unpredictable with microthrombi-driven risks^2-5

The pathophysiology of aTTP poses a triple threat^2,6-11

PEX and immunosuppression directly address only 2 of the 3 aspects of the disease^2,7-9

ADAMTS13=a disintegrin and metalloproteinase with a thrombospondin type 1 motif, 13; ULvWF=ultra-large von Willebrand factor; vWF=von Willebrand factor.

Risk remains in aTTP if PEX and immunosuppression are used alone

Treating aTTP with PEX and immunosuppression alone does not have an immediate effect on platelet aggregation, leaving patients at risk of ongoing microvascular thrombosis and its acute and long-term consequences.¹²

MORTALITY REMAINS HIGH^9,13,14

Up to 20% of patients die despite receiving PEX and immunosuppression, with most deaths occurring within 14 days of diagnosis (median 9 days)^*

ORGAN DAMAGE CAUSED BY ISCHEMIA DUE TO MICROTHROMBI FORMATION IS COMMON¹³

Nearly 35% of in-hospital TTP deaths were related to ischemia, including MI and stroke, despite receiving PEX^†

EXACERBATION AND RELAPSE ARE UNPREDICTABLE AND POSE A THREAT TO PATIENTS^3,9,15-19

More than 50% of patients have ≥1 recurrence within 30 days of stopping PEX (median time to flare-up is 10 days)‡

84% of patients have a relapse in their lifetime, often within 1-2 years, but relapses can be seen up to 30 years later

INCREASED STROKE RISKS THROUGH CLINICAL REMISSION²⁰

Stroke after recovery with PEX occurred in 27.6% (8/29) of patients with ADAMTS13 activity ≤70% (P=0.007)^§

REFRACTORY DISEASE IS COMMON^7,16,21

Up to 42% of patients are refractory to PEX and immunosuppression, which is associated with worse outcomes

Mortality rates are similar for patients with de novo and relapsed disease.³
To help prevent early death, it is not recommended to wait for ADAMTS13 assay results to initiate treatment^1,11,22||

*Literature review of studies with more than 100 patients with TTP.
†Retrospective claims analysis of hospitalizations with TTP (N=8203).
‡Retrospective review of CNR-MAT Registry (N=388).
§Cohort study of 170 patients with aTTP from 1995 to 2018.
||In settings with timely access to plasma ADAMTS13 activity testing and for patients with a high clinical suspicion (≥90% pretest probability of aTTP).
ADAMTS13=a disintegrin and metalloproteinase with a thrombospondin type 1 motif, 13; CNR-MAT=French Reference Centre for Thrombotic Microangiopathies; MI=myocardial infarction.

Zheng XL, Vesely SK, Cataland SR, et al. ISTH guidelines for the diagnosis of thrombotic thrombocytopenic purpura. J Thromb Haemost. 2020;18(10):2486-2495. doi:10.1111/ jth.15006
Scully M, Cataland SR, Peyvandi F, et al; HERCULES Investigators. Caplacizumab treatment for acquired thrombotic thrombocytopenic purpura. N Engl J Med. 2019;380(4):335-346. doi:10.1056/NEJMoa1806311
Masias C, Wu H, McGookey M, Jay L, Cataland S, Yang S. No major differences in outcomes between the initial and relapse episodes in patients with thrombotic thrombocytopenic purpura: the experience from the Ohio State University Registry. Am J Hematol. 2018;93(3):E73-E75. doi:10.1002/ajh.25002
Schieppati F, Russo L, Marchetti M, et al. Low levels of ADAMTS-13 with high anti-ADAMTS-13 antibodies during remission of immune-mediated thrombotic thrombocytopenic purpura highly predict for disease relapse: a multi-institutional study. Am J Hematol. 2020;95(8):953-959. doi:10.1002/ajh.25845
Knoebl P, Cataland S, Peyvandi F, et al. Efficacy and safety of open-label caplacizumab in patients with exacerbations of acquired thrombotic thrombocytopenic purpura in the HERCULES study. J Thromb Haemost. 2020;18(2):479-484. doi:10.1111/jth.14679
Joly BS, Coppo P, Veyradier A. Thrombotic thrombocytopenic purpura. Blood. 2017;129(21):2836-2846. doi:10.1182/blood-2016-10-709857
Sayani FA, Abrams CS. How I treat refractory thrombotic thrombocytopenic purpura. Blood. 2015;125(25):3860-3867. doi:10.1182/blood-2014-11-551580
Scully M, Hunt BJ, Benjamin S, et al; 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):323-335. doi:10.1111/j.1365-2141.2012.09167.x
Kremer Hovinga JA, Coppo P, Lämmle B, Moake JL, Miyata T, Vanhoorelbeke K. Thrombotic thrombocytopenic purpura. Nat Rev Dis Primers. 2017;3:17020. doi:10.1038/ nrdp.2017.20
Holz J-B. The TITAN trial—assessing the efficacy and safety of an anti-von Willebrand factor Nanobody in patients with acquired thrombotic thrombocytopenic purpura. Transfus Apher Sci. 2012;46(3):343-346. doi:10.1016/j.transci.2012.03.027
Azoulay E, Bauer PR, Mariotte E, et al; Nine-i Investigators. Expert statement on the ICU management of patients with thrombotic thrombocytopenic purpura. Intensive Care Med. 2019;45(11):1518-1539. doi:10.1007/s00134-019-05736-5
Sargentini-Maier ML, De Decker P, Tersteeg C, et al. Clinical pharmacology of caplacizumab for the treatment of patients with acquired thrombotic thrombocytopenic purpura. Expert Rev Clin Pharmacol. 2019;12(6):537-545. doi:10.1080/17512433.2019.1607293
Goel R, King KE, Takemoto CM, Ness PM, Tobian AAR. Prognostic risk-stratified score for predicting mortality in hospitalized patients with thrombotic thrombocytopenic purpura: nationally representative data from 2007 to 2012. Transfusion. 2016;56(6):1451-1458. doi:10.1111/trf.13586
Benhamou Y, Assié C, Boelle P-Y, et al. Development and validation of a predictive model for death in acquired severe ADAMTS13 deficiency-associated idiopathic thrombotic thrombocytopenic purpura: the French TMA Reference Center experience. Haematologica. 2012;97(8):1181-1186. doi:10.3324/haematol.2011.049676
Grall M, Azoulay E, Galicier L, et al. Thrombotic thrombocytopenic purpura misdiagnosed as autoimmune cytopenia: causes of diagnostic errors and consequence on outcome. Experience of the French Thrombotic Microangiopathies Reference Centre. Am J Hematol. 2017;92(4):381-387. doi:10.1002/ajh.24665
Coppo P, Cuker A, George JN. Thrombotic thrombocytopenic purpura: toward targeted therapy and precision medicine. Res Pract Thromb Haemost. 2018;3(1):26-37. doi:10.1002/rth2.12160
Hie M, Gay J, Galicier L, et al. Preemptive rituximab infusions after remission efficiently prevent relapses in acquired thrombotic thrombocytopenic purpura. Blood. 2014;124(2):204-210. doi:10.1182/blood-2014-01-550244
Thejeel B, Garg AX, Clark WF, et al. Long-term outcomes of thrombotic microangiopathy treated with plasma exchange: a systematic review. Am J Hematol. 2016;91(6):623-630. doi:10.1002/ajh.24339
Falter T, Alber KJ, Scharrer I. Long term outcome and sequelae in patients after acute thrombotic thrombocytopenic purpura episodes. Hämostaseologie. 2013;33(2):113-120. doi:10.5482/HAMO-12-11-0019
Upreti H, Kasmani J, Dane K, et al. Reduced ADAMTS13 activity during TTP remission is associated with stroke in TTP survivors. Blood. 2019;134(13):1037-1045. doi:10.1182/blood.2019001056
Peyvandi F, Cataland S, Scully M, et al. Caplacizumab prevents refractoriness and mortality in acquired thrombotic thrombocytopenic purpura: integrated analysis. Blood Adv. 2021;5(8):2137-2141. doi:10.1182/bloodadvances.2020001834
Zheng XL, Vesely SK, Cataland SR, et al. ISTH guidelines for treatment of thrombotic thrombocytopenic purpura. J Thromb Haemost. 2020;18(10):2496-2502. doi:10.1111/ jth.15010
CABLIVI. Summary of Product Characteristics (SmPC). Sanofi.
Ulrichts H, Silence K, Schoolmeester A, et al. Antithrombotic drug candidate ALX-0081 shows superior preclinical efficacy and safety compared with currently marketed antiplatelet drugs. Blood. 2011;118(3):757-765. doi:10.1182/blood-2010-11-317859
Peyvandi F, Scully M, Kremer Hovinga JA, et al; TITAN Investigators. Caplacizumab for acquired thrombotic thrombocytopenic purpura. N Engl J Med. 2016;374(6):511-522. doi:10.1056/NEJMoa1505533
Bendapudi PK, Hurwitz S, Fry A, et al. Derivation and external validation of the PLASMIC score for rapid assessment of adults with thrombotic microangiopathies: a cohort study. Lancet Haematol. 2017;4(4):e157-e164. doi:10.1016/S2352-3026(17)30026-1

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Mechanism of Disease

Each aTTP episode can be unpredictable with microthrombi-driven risks2-5

Risk remains in aTTP if PEX and immunosuppression are used alone

References

Each aTTP episode can be unpredictable with microthrombi-driven risks^2-5