How to diagnose thrombotic thrombocytopenic purpura (TTP)

Diagnosing TTP rapidly is critical and can save a life1

When a patient presents with2
Severe thrombocytopenia

Severe thrombocytopenia

(often platelets <30 × 109/L)

Microangiopathic hemolytic anaemia (MAHA

Microangiopathic hemolytic anemia (MAHA)

characterized by the presence of schistocytes in blood smear

With no identified cause

With no identified cause

The risk of death is acute and imminent if TTP remains undiagnosed and untreated1,3,4
Mortality occurs in 90% of treated patients.

of untreated patients1,3,4

Mortality can occur within hours of the acute event if untreated.

of the acute event if untreated1

Why TTP can be difficult to diagnose

TTP is rare and presents similarly to other thrombotic microangiopathies (TMAs), making it a challenge to diagnose. All TMAs result in thrombosis of capillaries and arterioles due to endothelial injury.5,6

A delay in diagnosing TTP can leave patients at risk for organ damage and death. The uncertainty around what’s happening to these patients can cause fear and frustration.5,7-9

It's critical to differentiate TTP from other TMAs quickly so patients can get started on appropriate treatment
Diagnosing TTP in adults: Step-by-step1,7,10-15
Presentation
Neurological symptoms

Headache and/or confusion and/or seizures and/or other cerebral abnormalities

Gastrointestinal symptoms

Abdominal pain, nausea, and diarrhea

Cardiac symptoms

Chest pain and/or hypotension and/or myocardial infarction and/or congestive heart failure and/or sudden cardiac arrest and/or other cardiac abnormalities

Renal impairment

Hematuria and proteinuria; creatinine <2 mg/dL; typically not severe

Diagnosing aTTP?

Clinical Diagnosisinfo icon
SUSPECTED TMA
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MAHA* and thrombocytopenia confirmed
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Known underlying or associated condition?
NO
YESinfo icon
  • DIC
  • Infection
  • Malignancy
  • Preeclampsia/HELLP syndrome
  • Severe hypertension
  • Systemic rheumatic disease
  • Hematopoietic cell transplant
  • Solid organ transplant
This list is not inclusive of all potential conditions.
DIC=disseminated intravascular coagulation; HELLP=Hemolysis, Elevated Liver enzymes and Low Platelets.
Kidney injury
NO/MINIMAL
ACUTEinfo icon
CHRONICinfo icon
Message 1
  • Drug-induced TMA (immune)
  • Shiga-toxin HUS
  • Complement-mediated TMA
  • Metabolism-mediated TMA
  • Coagulation-mediated TMA
  • TTP (less likely)
HUS=hemolytic uremic syndrome; TMA=thrombotic microangiopathy; TTP=thrombotic thrombocytopenic purpura.
Drug-induced TMA (non-immune)
TMA=thrombotic microangiopathy.
TTP clinical diagnosis

With a clinical diagnosis, TTP treatment should begin immediately while awaiting confirmatory diagnosis. This helps ensure patients receive care promptly.

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Begin TTP treatment
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ADAMTS13info icon  test results
<10%
10%-20%info icon
>20%info icon
Use clinical judgment to guide treatment or consider other diagnoses
Consider other diagnoses
TTP confirmed
*Evidence of MAHA includes hemoglobin and hematocrit below reference range, low haptoglobin, elevated LDH, and presence of schistocytes in blood smear.
Kidney injury has been reported in 25% of patients with aTTP in the Oklahoma TTP-HUS Registry.15
Dr Maria Scully

Diagnosing TTP

Dr Marie Scully shares details on how to make a prompt differential diagnosis of TTP.

Important TTP lab markers
The presence of schistocytes on the blood smear is the morphologic hallmark of the disease, but the absence of schistocytes does not rule out TTP.

The presence of schistocytes on the blood smear is the morphologic hallmark of the disease, but the absence of schistocytes does not rule out TTP.2,16

Although serum creatinine is typically <2.0 mg/dL at presentation, the Oklahoma TTP-HUS Registry reported kidney injury 25% of the time

Although serum creatinine is typically <2.0 mg/dL at presentation, the Oklahoma TTP-HUS Registry reported kidney injury 25% of the time.2,15

While not diagnostic, elevated LDH may be predictive of severe organ damage, and elevated troponin may indicate cardiovascular risk

While not diagnostic, elevated LDH may be predictive of severe organ damage, and elevated troponin may indicate cardiovascular risk.1,2

ADAMTS13 activity <10% confirms a TTP diagnosis and supports TTP treatment, but ADAMTS13 levels of 10% to 20%donotruleoutTTP. TTPmanagementwillrelyon clinical judgement.

ADAMTS13 activity <10% confirms a TTP diagnosis and supports TTP treatment, but ADAMTS13 levels of 10% to 20% do not rule out TTP. TTP management will rely on clinical judgment.2,7,13

ADAMTS13 <10% confirms TTP.
Test as soon as possible when TMA is suspected.2,7,13
LDH=lactose dehydrogenase; MAHA=microangiopathic hemolytic anemia; TMA=thrombotic microangiopathy; 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. Joly BS, Coppo P, Veyradier A. Thrombotic thrombocytopenic purpura. Blood. 2017;129(21):2836-2846. doi:10.1182/blood-2016-10-709857
  3. 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
  4. Sayani FA, Abrams CS. How I treat refractory thrombotic thrombocytopenic purpura. Blood. 2015;125(25):3860-3867. doi:10.1182/blood-2014-11-551580
  5. 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
  6. Tsai H-M. Pathophysiology of thrombotic thrombocytopenic purpura. Int J Hematol. 2010;91(1):1-19. doi:10.1007/s12185-009-0476-1
  7. 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
  8. Grall M, Azoulay E, Galicier L, et al. Thrombotic thrombocytopenic purpura misdiagnosed as autoimmune cytopenia: causes of diagnostic errors and consequence on outcome. Experience of the French Thrombotic Microangiopathies Reference Centre. Am J Hematol. 2017;92(4):381-387. doi:10.1002/ajh.24665
  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. Sukumar S, Lämmle B, Cataland SR. Thrombotic thrombocytopenic purpura: pathophysiology, diagnosis, and management. J Clin Med. 2021;10(3):536. doi:10.3390/jcm10030536
  11. Wiernek SL, Jiang B, Gustafson GM, Dai X. Cardiac implications of thrombotic thrombocytopenic purpura. World J Cardiol. 2018;10(12):254-266.
  12. Hawkins BM, Abu-Fadel M, Vesely SK, George JN. Clinical cardiac involvement in thrombotic thrombocytopenic purpura: a systematic review. Transfusion. 2008;48:382-392. doi:10.1111/j.1537-2995.2007.01534.x
  13. Supplement to (Acquired TTP): George JN. The remarkable diversity of thrombotic thrombocytopenic purpura: a perspective. Blood Adv. 2018;2(12):1510-1516. doi:10.1182/bloodadvances.2018018432
  14. Supplement to (Approach to Patient): George JN. The remarkable diversity of thrombotic thrombocytopenic purpura: a perspective. Blood Adv. 2018;2(12):1510-1516. doi:10.1182/bloodadvances.2018018432
  15. George JN. The remarkable diversity of thrombotic thrombocytopenic purpura: a perspective. Blood Adv. 2018;2(12):1510-1516. doi:10.1182/bloodadvances.2018018432
  16. 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