What are the acute TTP episodes?

3 min

Acute episodes
  • Acute TTP is a life-threatening emergency associated with a mortality risk of 10–20% despite current treatment, and a high risk of recurrence and if untreated multi-organ ischemia.1,2
  • Intensive care unit (ICU) admission varies between 40% and 100% for acute TTP.3
  • Both cTTP and iTTP can present with ischemic stroke.4,5
Diagram of red outlined human body and internal organs with text box annotations of TTP symptoms linked to respective organs
Diagram of red outlined human body and internal organs with text box annotations of TTP symptoms linked to respective organs
Diagram of red outlined human body and internal organs with text box annotations of TTP symptoms linked to respective organs

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Abbreviations, Glossary and References

Abbreviations

CNS; Central nervous system

cTTP; Congenital TTP

ECG; Echocardiogram

ICU; Intensive care unit

iTTP; Immune-mediated TTP

MAHA; Microangiopathic hemolytic anemia

RBC; Red blood cells

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.2,7

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.8

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.9

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.10

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.11

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.12

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.13,14

 

References

  1. Joly, B.S., P. Coppo, and A. Veyradier, Thrombotic thrombocytopenic purpura. Blood, 2017. 129(21): p. 2836-2846.
  2. Kremer Hovinga, J.A., et al., Thrombotic thrombocytopenic purpura. Nat Rev Dis Primers, 2017. 3: p. 17020.
  3. Fodil, S. and L. Zafrani, Severe Thrombotic Thrombocytopenic Purpura (TTP) with Organ Failure in Critically Ill Patients. Journal of Clinical Medicine, 2022. 11(4): p. 1103.
  4. Beltrami-Moreira, M. and M.T. DeSancho, Delayed diagnosis of congenital thrombotic thrombocytopenic purpura in a patient with recurrent strokes. J Thromb Thrombolysis, 2022. 53(3): p. 734-738.
  5. Lin, C., et al., Identification of Biomarkers in Patients with Thrombotic Thrombocytopenic Purpura Presenting with Large and Small Ischemic Stroke. Cerebrovasc Dis Extra, 2021. 11(1): p. 29-36.
  6. Scully, M.A. and S.R. Cataland, Fast Facts: Thrombotic Thrombocytopenic Purpura: Prompt action saves lives. 2020.
  7. 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.
  8. 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.
  9. Zini, G., et al., ICSH recommendations for identification, diagnostic value, and quantitation of schistocytes. Int J Lab Hematol, 2012. 34(2): p. 107-116.
  10. Gauer, R.L. and M.M. Braun, Thrombocytopenia. Am Fam Physician, 2012. 85(6): p. 612-622.
  11. George, J.N. and C.M. Nester, Syndromes of thrombotic microangiopathy. N Engl J Med, 2014. 371(7): p. 654-666.
  12. 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.
  13. Rauch, A., et al., On the versatility of von Willebrand factor. Mediterr J Hematol Infect Dis, 2013. 5(1): p. e2013046.
  14. 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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