What are the benefits and challenges of ADAMTS13 monitoring?

3 min

ADAMTS13
Diagnosis/monitoring
Treatment
Grey table with red bullets/black text explaining ADAMTS13 activity monitoring benefits for cTTP prognosis and management
Grey table with red bullets/black text explaining ADAMTS13 activity monitoring benefits for cTTP prognosis and management
Grey table with red bullets/black text explaining ADAMTS13 activity monitoring benefits for cTTP prognosis and management
Grey table with red bullets/black text explaining the challenges of cTTP diagnosis and ADAMTS13 activity monitoring
Grey table with red bullets/black text explaining the challenges of cTTP diagnosis and ADAMTS13 activity monitoring
Grey table with red bullets/black text explaining the challenges of cTTP diagnosis and ADAMTS13 activity monitoring

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Abbreviations, Glossary and References

Abbreviations

ADAMTS13; A disintegrin and metalloproteinase with a thrombospondin motifs 13

cTTP; Congenital TTP

iTTP; Immune-mediated TTP

QoL; Quality of life

TTP; Thrombotic thrombocytopenic purpura

 

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.8,9

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.10

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.11

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.12

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.13

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.14

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.15,16

 

 

References

  1. Sukumar, S., B. Lammle, and S.R. Cataland, Thrombotic Thrombocytopenic Purpura: Pathophysiology, Diagnosis, and Management. J Clin Med, 2021. 10(3): p. 536.
  2. Roose, E. and B.S. Joly, Current and Future Perspectives on ADAMTS13 and Thrombotic Thrombocytopenic Purpura. Hamostaseologie, 2020. 40(3): p. 322-336.
  3. 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.
  4. Kucukyurt, S. and A.E. Eskazan, Assessment and Monitoring of Patients with Immune-Mediated Thrombotic Thrombocytopenic Purpura (iTTP): Strategies to Improve Outcomes. J Blood Med, 2020. 11: p. 319-326.
  5. Novelli, C., et al., Clinical and Economic Impacts of a New Rapid ADAMTS-13 Assay for the Diagnosis of Suspected Thrombotic Thrombocytopenic Purpura. ISTH 2020 Congress, 2020.
  6. Mackie, I., et al., International Council for Standardization in Haematology (ICSH) recommendations for laboratory measurement of ADAMTS13. Int J Lab Hematol, 2020. 42(6): p. 685-696.
  7. Stratmann, J., J.N. Ward, and W. Miesbach, Evaluation of a rapid turn-over, fully-automated ADAMTS13 activity assay: a method comparison study. J Thromb Thrombolysis, 2020. 50(3): p. 628-631.
  8. 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.
  9. Kremer Hovinga, J.A., et al., Thrombotic thrombocytopenic purpura. Nat Rev Dis Primers, 2017. 3: p. 17020.
  10. 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.
  11. Zini, G., et al., ICSH recommendations for identification, diagnostic value, and quantitation of schistocytes. Int J Lab Hematol, 2012. 34(2): p. 107-116.
  12. Gauer, R.L. and M.M. Braun, Thrombocytopenia. Am Fam Physician, 2012. 85(6): p. 612-622.
  13. George, J.N. and C.M. Nester, Syndromes of thrombotic microangiopathy. N Engl J Med, 2014. 371(7): p. 654-666.
  14. 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.
  15. Rauch, A., et al., On the versatility of von Willebrand factor. Mediterr J Hematol Infect Dis, 2013. 5(1): p. e2013046.
  16. 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.
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