What is TTP?

Thrombotic thrombocytopenic purpura (TTP)—
A rare, life-threatening medical emergency

TTP is a rare, life-threatening thrombotic microangiopathy (TMA). There are approximately 3 cases per million people.1,2

The name thrombotic thrombocytopenic purpura describes the 3 main characteristics of the disease.

Thrombotic

Thrombotic: characterized by the formation of microthrombi (blood clots) within a blood vessel, which clog the vessel and prevent blood circulation.

Thrombocy topenic

Thrombocytopenic: a lower-than-normal platelet count due to the consumption of platelets during microthrombi formation, which causes occlusion of microvasculature.

Purpura

Purpura: spots of variable size on the skin or in the mucous membranes, due to small hemorrhages; they can be dark red and as small as a pinhead (petechiae) or purplish and 2 to 3 cm in diameter (ecchymosis).

Types of TTP

Acquired TTP3,4

  • aTTP, also known as immune-mediated thrombotic thrombocytopenic purpura (iTTP)
  • The most common form of TTP; approximately 95% of TTP cases are aTTP
  • Caused by autoantibody inhibition of ADAMTS13info icon activity

Hereditary TTP4,5

  • Also known as congenital TTP, inherited TTP, familial TTP, or Upshaw–Schulman syndrome
  • Very rare form of TTP; mainly detected in children
  • Caused by mutations in the ADAMTS13 gene

Primary aTTP vs secondary aTTP2,6,7

Primary aTTP

  • Primary aTTP refers to acquired autoimmune TTP for which there is no obvious underlying/precipitating cause/disease
  • Primary aTTP accounts for the majority of cases of TTP

Secondary aTTP

  • Secondary aTTP refers to acquired autoimmune TTP for which a defined underlying disorder or trigger can be identified, including connective tissue disease (eg, systemic lupus erythematosus), HIV infection, cytomegalovirus infection, and/or a specific precipitating factor (eg, pregnancy or drugs)
  • Treatment of the underlying disorder and/or removal of the underlying precipitant may be required, as well as standard TTP therapy

TTP causes systemic microthrombi and consequent thrombocytopenia, hemolytic anemia, and organ ischemia. These symptoms—coupled with TTP’s rarity—can cause confusion with other TMAs, making TTP a challenge to diagnose.8-10

Signs and symptoms of aTTP include1,7-10

Petechiae, purpura, bruising (skin)

Headache, confusion, seizures, coma (neurological)

EKG abnormalities (cardiac)

Abdominal pain, diarrhea (gastrointestinal)

Proteinuria/hematuria (kidney)

Suspect aTTP?

The incidence of TTP is 2 to 6 per million individuals4

Rare diseases defined as

<500

cases
per
million11

Ultra-rare diseases defined as

<20

cases
per
million12

aTTP primarily affects young, healthy adults13,14

30 to 50 years of age on average

years of age on average

Up to 75% of people affected are women

of people affected are women

7 times higher TTP incidence in the Black population

higher aTTP incidence
in the Black population

If left untreated, TTP is rapidly fatal8,15-17

Over 90% acute mortality rate

acute mortality rate16,17

Approximately50%ofTTPdeathsoccurwithin24hoursof presentation.

of TTP deaths occur within
24 hours of presentation8

Even with plasma exchange therapy (PEX), mortality risk persists15,16,18

Up to

20%

acute mortality
associated with
episodes of aTTP16,18

9 days

median time
from diagnosis
to death

in acute phase of TTP in patients treated with PEX15,18

median time from diagnosis to death in acute phase of TTP in patients treated with PEX15,18

References:
  1. Joly BS, Coppo P, Veyradier A. Thrombotic thrombocytopenic purpura. Blood. 2017;129(21):2836-2846. doi:10.1182/blood-2016-10-709857
  2. Arnold DM, Patriquin CJ, Nazy I. Thrombotic microangiopathies: a general approach to diagnosis and management. CMAJ. 2017;189(4):E153-E159. doi:10.1503/cmaj.160142
  3. 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
  4. 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
  5. National Institutes of Health. Congenital thrombotic thrombocytopenic purpura. Updated July 12, 2018. Accessed February 15, 2022. https://rarediseases.info.nih.gov/diseases/9430/congenital-thrombotic-thrombocytopenic-purpura
  6. Sukumar S, Lämmle B, Cataland SR. Thrombotic thrombocytopenic purpura: pathophysiology, diagnosis, and management. J Clin Med. 2021;10(3):536. doi:10.3390/jcm10030536
  7. 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
  8. 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
  9. Gallan AJ, Chang A. A new paradigm for renal thrombotic microangiopathy. Semin Diagn Pathol. 2020;37(3):121-126. doi:10.1053/j.semdp.2020.01.002
  10. Tsai H-M. Pathophysiology of thrombotic thrombocytopenic purpura. Int J Hematol. 2010;91(1):1-19. doi:10.1007/s12185-009-0476-1
  11. Kaplan W, Wirtz VJ, Mantel-Teeuwisse A, Stolk P, Duthey B, Laing R. Rare diseases. In: Priority Medicines for Europe and the World. 2013 Update. Chap 6.19. World Health Organization. Accessed January 27, 2022. https://www.who.int/medicines/areas/priority_medicines/MasterDocJune28_FINAL_Web.pdf?ua=1
  12. Harari S, Humbert M. Ultra-rare disease: an European perspective. Eur Respir Rev. 2020;29(156):200195. doi:10.1183/16000617.0195-2020
  13. Terrell DR, Williams LA, Vesely SK, Lämmle B, Hovinga JAK, George JN. The incidence of thrombotic thrombocytopenic purpura-hemolytic uremic syndrome: all patients, idiopathic patients, and patients with severe ADAMTS-13 deficiency. J Thromb Haemost. 2005;3(7):1432-1436. doi:10.1111/j.1538-7836.2005.01436.x
  14. Reese JA, Muthurajah DS, Kremer Hovinga JA, Vesely SK, Terrell DR, George JN. Children and adults with thrombotic thrombocytopenic purpura associated with severe, acquired Adamts13 deficiency: comparison of incidence, demographic and clinical features. Pediatr Blood Cancer. 2013;60(10):1676-1682. doi:10.1002/pbc.24612
  15. 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
  16. 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
  17. Sayani FA, Abrams CS. How I treat refractory thrombotic thrombocytopenic purpura. Blood. 2015;125(25):3860-3867. doi:10.1182/blood-2014-11-551580
  18. Peyvandi F, Scully M, Kremer Hovinga JA, et al. Caplacizumab reduces the frequency of major thromboembolic events, exacerbations and death in patients with acquired thrombotic thrombocytopenic purpura. J Thromb Haemost. 2017;15(7):1448-1452. doi:10.1111/jth.13716