The USTMA created this consensus document to guide hematologists in the Diagnosis and treatment of immune mediated TTP (iTTP).

High clinical suspicion of immune mediated TTP (iTTP) is defined as:

Thrombocytopenia:  platelet count < 100,000 and

Microangiopathic hemolytic anemia1-2: two or more of the following criteria’s

  • elevated absolute reticulocytes count > 100,000/uL

  • elevated indirect bilirubin  

  • undetectable haptoglobin

  • elevated LDH

  • schistocytes in blood smear:

  • Direct Antiglobulin Test ( DAT or Coombs): negative

ADAMTS-13 activity < 10% and the presence of ADAMTS-13 inhibitor or antibody

 

If the diagnosis is uncertain and/or ADAMTS-13 is not available, the USTMA suggests the use of the PLASMIC score4, a clinical prediction tool, as an adjunct to clinical judgment and to guide initial management of patients with TMA (thrombotic microangiopathy). The PLASMIC score does NOT confirm or exclude the diagnosis of iTTP and does not take in consideration patients with comorbidities5.

 

Testing

 Lab tests prior to initiation of plasma exchange:

  • For all patients send: ADAMTS-13 activity, ADAMTS-13 antibody or inhibitor titer, and a citrate tube in case of additional testing is needed

  • Other supporting tests based on clinical presentation:

  • DIC panel

  • Troponin as a prognostic indicator

  • Hepatitis B panel

  • Pregnancy test

Additional testing in the pediatric population:

  • Lupus anticoagulant

  • ANA, ds DNA and antiphospholipid antibodies

  • C3 and C4

  • Shiga Toxin PCR

If ADAMTS-13 is normal and/or creatinine is > 2.25 then

  • Shiga Toxin and stool cultures

 

If you still have questions about the diagnosis, then the USTMA suggests referring the patient to the closest academic center to assist with further evaluation.

 

Immediate transfer should be made to a center with plasmapheresis capabilities once the diagnosis of iTTP is suspected even if the diagnosis is not yet confirmed.

References:

1. Burns ER, Lou Y, Pathak A. Morphologic Diagnosis of Thrombotic Thrombocytopenic Purpura. American Journal of Hematology 75:18–21 (2004)

2. Barcellini W, Fattizzo B.Clinical Applications of Hemolytic Markers in the Differential Diagnosis and Management of Hemolytic Anemia. Dis Markers. 2015; 2015: 635670.

3. ISTH TTP guidelines https://www.isth.org

4. Bendapudi P.K., Hurwitz S., Fry A., Marques M.B., Waldo S.W., Li A. Derivation and external validation of the PLASMIC score for rapid assessment of adults with thrombotic microangiopathies: a cohort study. Lancet Haematol. 2017;4:157–164.

5.Chiasakul T, Cuker A. Clinical and laboratory diagnosis of TTP: an integrated approach. Am Soc Hematol Educ Program 2018 (1): 530–538.