What are the consequences of TTP?

Abbreviations

ADAMTS13; A disintegrin and metalloproteinase with a thrombospondin motifs 13

QoL; Quality of life

TTP; Thrombotic thrombocytopenic purpura

VWF; Von Willebrand factor

Glossary

ADAMTS13; ADAMTS13 (A Disintegrin And Metalloprotease with ThromboSpondin motifs 13) is a constitutively active enzyme (plasma metalloprotease) that catalyzes the breakdown of ultra large and high molecular weight von Willebrand factor (VWF) into smaller multimers, reducing their thrombogenic potential, and maintaining hemostasis.^1,14

Incidence; The rate of new cases or events over a specified period for the population at risk for a certain event.

Microangiopathic hemolytic anemia (MAHA); Process of red blood cell destruction within the microvasculature accompanied by thrombocytopenia due to platelet activation and consumption. Thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS) are primary forms of thrombotic microangiopathies.¹⁵

Prevalence; The proportion of a particular population found to be affected by a medical condition at a specific time.

Schistocyte; Circulating fragments of red blood cells commonly seen in blood smears from patients with thrombotic microangiopathies including TTP.¹⁶

Thrombocytopenia; Refers to a state of reduced peripheral platelets below normal levels (150x10⁹/L) and can be caused by a wide variety of aetiologies that either decrease platelet production or increase platelet consumption.¹⁷

Thrombotic microangiopathy (TMA); TMA includes a diverse set of syndromes that can be hereditary or acquired, which can occur in children and adults with sudden or gradual onset.

TMA syndromes, despite being diverse, have a common set of clinical and pathological features: MAHA, thrombocytopenia, organ injury, vascular damage manifested by arteriolar and capillary thrombosis with characteristic abnormalities in the endothelium and vessel wall.¹⁸

Thrombotic thrombocytopenic purpura (TTP); TTP is a type of MAHA presenting with moderate or severe thrombocytopenia. There is associated organ dysfunction, including neurologic, cardiac, gastrointestinal and renal involvement; oliguria or anuric renal failure requiring renal replacement therapy is not typically a feature. TTP is confirmed by a severe deficiency (<10%) of ADAMTS13 activity.²

von Willebrand factor (VWF); VWF plays two key roles in hemostasis: 1) in primary (platelet-mediated) hemostasis, VWF binds to collagen and platelets thus promoting platelet activation and aggregation, and 2) in secondary (coagulation factor mediated) hemostasis VWF binds factor VIII (FVIII) protecting FVIII from rapid clearance. When VWF binds to collagen following vascular injury, it releases FVIII, leading to FVIII activation and initiation of the coagulation cascade.^19,20

References

1. Kremer Hovinga, J.A., et al., Thrombotic thrombocytopenic purpura. Nat Rev Dis Primers, 2017. 3: p. 17020.
2. Scully, M., et al., Consensus on the standardization of terminology in thrombotic thrombocytopenic purpura and related thrombotic microangiopathies. J Thromb Haemost, 2017. 15(2): p. 312-322.
3. Alwan, F., et al., Characterization and treatment of congenital thrombotic thrombocytopenic purpura. Blood, 2019. 133(15): p. 1644-1651.
4. Blombery, P. and M. Scully, Management of thrombotic thrombocytopenic purpura: current perspectives. J Blood Med, 2014. 5: p. 15-23.
5. Scully, M.A. and S.R. Cataland, Fast Facts: Thrombotic Thrombocytopenic Purpura: Prompt action saves lives. 2020.
6. Holmes, S., et al., Survival after acute episodes of immune-mediated thrombotic thrombocytopenic purpura (iTTP) - cognitive functioning and health-related quality of life impact: a descriptive cross-sectional survey of adults living with iTTP in the United Kingdom. Hematology, 2021. 26(1): p. 465-472.
7. George, J.N., TTP: long-term outcomes following recovery. Hematology Am Soc Hematol Educ Program, 2018. 2018(1): p. 548-552.
8. Alwan, F., et al., Cerebral MRI findings predict the risk of cognitive impairment in thrombotic thrombocytopenic purpura. Br J Haematol, 2020. 191(5): p. 868-874.
9. Shaw, R.J. and T. Dutt, Mind and matter: The neurological complications of thrombotic thrombocytopenic purpura. Br J Haematol, 2022. 197(5): p. 529-538.
10. Deford, C.C., et al., Multiple major morbidities and increased mortality during long-term follow-up after recovery from thrombotic thrombocytopenic purpura. Blood, 2013. 122(12): p. 2023-2029.
11. Upreti, H., et al., Reduced ADAMTS13 activity during TTP remission is associated with stroke in TTP survivors. Blood, 2019. 134(13): p. 1037-1045.
12. Chaturvedi, S., H. Abbas, and K.R. McCrae, Increased morbidity during long-term follow-up of survivors of thrombotic thrombocytopenic purpura. Am J Hematol, 2015. 90(10): p. E208.
13. Sukumar, S., et al., Cardiovascular disease is a leading cause of mortality among TTP survivors in clinical remission. Blood Adv, 2022. 6(4): p. 1264-1270.
14. Markham-Lee, Z., N.V. Morgan, and J. Emsley, Inherited ADAMTS13 mutations associated with Thrombotic Thrombocytopenic Purpura: a short review and update. Platelets, 2023. 34(1): p. 2138306.
15. Arnold, D.M., C.J. Patriquin, and I. Nazy, Thrombotic microangiopathies: a general approach to diagnosis and management. CMAJ, 2017. 189(4): p. E153-E159.
16. Zini, G., et al., ICSH recommendations for identification, diagnostic value, and quantitation of schistocytes. Int J Lab Hematol, 2012. 34(2): p. 107-116.
17. Gauer, R.L. and M.M. Braun, Thrombocytopenia. Am Fam Physician, 2012. 85(6): p. 612-622.
18. George, J.N. and C.M. Nester, Syndromes of thrombotic microangiopathy. N Engl J Med, 2014. 371(7): p. 654-666.
19. Rauch, A., et al., On the versatility of von Willebrand factor. Mediterr J Hematol Infect Dis, 2013. 5(1): p. e2013046.
20. Stockschlaeder, M., R. Schneppenheim, and U. Budde, Update on von Willebrand factor multimers: focus on high-molecular-weight multimers and their role in hemostasis. Blood Coagul Fibrinolysis, 2014. 25(3): p. 206-216.