The burden of thrombotic thrombocytopenic purpura (TTP)

Short- and long-term implications threaten patients with aTTP

Short-term implications

Mortality

  • Untreated, aTTP has an acute mortality rate of up to 90%1-3
  • Approximately 55% to 80% of deaths among patients with aTTP occur within 2 weeks of diagnosis4-6
  • Significantly higher rates of in-hospital mortality have also been reported in patients with TTP and CV complications (19.7% vs 4.1%)7

Health-related quality of life

  • Rates of depression (10% to 73%) are considerably higher in patients following an episode of TTP, compared with both healthy individuals and reference populations8-12

Morbidity

  • Most common complications in patients hospitalized with TTP are CV complications (25%), such as stroke (10%), heart failure (8%), and acute coronary syndrome (6%)7

Economic burden

  • Short-term treatment of acute thromboembolism such as stroke, acute MI, or TIA requires multiple healthcare resources, including hospitalization with diagnostic tests (eg, CT scans), administration of thrombolytic and/or other drugs, admittance to intensive care/critical care unit, and/or ongoing specialist nursing care (eg, physiotherapy, speech therapy)13-15

An increased time at risk of microvascular thrombosis can lead to irreversible organ damage to the heart, brain, and kidneys16

Long-term implications

Mortality

  • 23-fold increase in mortality was observed in patients who did not reach a platelet recovery rate of 5 × 109/L per day by day 3 of PEX17
  • Inability to normalize platelet count over 7 days of PEX was associated with a significantly increased risk of death18

Health-related quality of life

  • Long-term outcomes are driven by the consequences of platelet aggregation, leading to systemic microvascular thrombosis7,19

Morbidity

  • Recovery following an acute episode of aTTP is not a resolution of symptoms but the beginning of a long-term morbidity burden: hypertension, stroke, and depression requiring pharmacological treatment were significantly greater for TTP survivors versus the age- and sex-matched US population8,9,20

Economic burden

  • Other long-term consequences that have been reported include neurocognitive impairment, depression, hypertension, headaches, and SLE; all require healthcare resources on an ongoing basis11,20

Long-term morbidity leads to suboptimal health-related quality of life, in both mental (anxiety, depression) and physical functioning, and potentially reduces life expectancy8,20

aTTP=acquired thrombotic thrombocytopenic purpura; CT=computed tomography; CV=cardiovascular; MI=myocardial infarction; PEX=plasma exchange; SLE=systemic lupus erythematosus; TIA=transient ischemic attack; TTP=thrombotic thrombocytopenic purpura.
References:
  1. 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
  2. Kremer Hovinga JA, Vesely SK, Terrell DR, Lämmle B, George JN. Survival and relapse in patients with thrombotic thrombocytopenic purpura. Blood. 2010;115(8):1500-1511. doi:10.1182/blood-2009-09-243790
  3. Sayani FA, Abrams CS. How I treat refractory thrombotic thrombocytopenic purpura. Blood. 2015;125(25):3860-3867. doi:10.1182/blood-2014-11-551580
  4. 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
  5. 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
  6. Chaturvedi S, Bhatia N. Predictors of survival in thrombotic thrombocytopenic purpura. Haematologica. 2013;98(5):e58. doi:10.3324/haematol.2012.079400
  7. Balasubramaniyam N, Yandrapalli S, Kolte D, Pemmasani G, Janakiram M, Frishman WH. Cardiovascular complications and their association with mortality in patients with thrombotic thrombocytopenic purpura. Am J Med. 2021;134(2):e89-e97. doi:10.1016/j.amjmed.2020.06.020
  8. Chaturvedi S, Abbas H, McCrae KR. Increased morbidity during long-term follow-up of survivors of thrombotic thrombocytopenic purpura. Am J Hematol. 2015;90(10):E208. doi:10.1002/ajh.24138
  9. Falter T, Schmitt V, Herold S, et al. Depression and cognitive deficits as long-term consequences of thrombotic thrombocytopenic purpura. Transfusion. 2017;57(5):1152-1162. doi:10.1111/trf.14060
  10. Han B, Page EE, Stewart LM, et al. Depression and cognitive impairment following recovery from thrombotic thrombocytopenic purpura. Am J Hematol. 2015;90(8):709-714. doi:10.1002/ajh.24060
  11. Riva S, Mancini I, Maino A, et al. Long-term neuropsychological sequelae, emotional wellbeing and quality of life in patients with acquired thrombotic thrombocytopenic purpura. Haematologica. 2020;105(7):1957-1962. doi:10.3324/haematol.2019.226423
  12. Alwan F, Mahdi D, Tayabali S, et al. Cerebral MRI findings predict the risk of cognitive impairment in thrombotic thrombocytopenic purpura. Br J Haematol. 2020;191(5):868-874. doi:10.1111/bjh.17126
  13. Hughes PA. Comprehensive care of adults with acute ischemic stroke. Crit Care Nurs Clin N Amer. 2011;23(4):661-675. doi:10.1016/j.ccell.2011.08.009
  14. Reed GW, Rossi JE, Cannon CP. Acute myocardial infarction. Lancet. 2017;389(10065):197-210. doi:10.1016/s0140-6736(16)30677-8
  15. Lau CS, Mak A. The socioeconomic burden of SLE. Nat Rev Rheumatol. 2009;5(7):400-404. doi:10.1038/nrrheum.2009.106
  16. 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
  17. Liu C, Kallogjeri D, Dynis M, Grossman BJ. Platelet recovery rate during plasma exchange predicts early and late responses in patients with thrombotic thrombocytopenic purpura. Transfusion. 2013(5):1096-1107. doi:10.1111/j.1537-2995.2012.03857.x
  18. Staley EM, Cao W, Pham HP, et al. Clinical factors and biomarkers predict outcome in patients with immune-mediated thrombotic thrombocytopenic purpura. Haematologica. 2019;104(1):166-175. doi:10.3324/haematol.2018.198275
  19. 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
  20. Deford CC, Reese JA, Schwartz LH, et al. Multiple major morbidities and increased mortality during long-term follow-up after recovery from thrombotic thrombocytopenic purpura. Blood. 2013;122(12):2023-2029. doi:10.1182/blood-2013-04-496752