Algorithm for the initial treatment of acquired, autoimmune thrombotic thrombocytopenic purpura (TTP)
Algorithm for the initial treatment of acquired, autoimmune thrombotic thrombocytopenic purpura (TTP)
This algorithm applies to individuals with a presumptive diagnosis of acquired, autoimmune TTP that is caused by autoantibody-induced ADAMTS13 deficiency. It should not be used for individuals with drug-induced TMA, hereditary TTP, or other causes of MAHA and thrombocytopenia such as malignancy or DIC. Refer to UpToDate for additional details.
TTP: thrombotic thrombocytopenic purpura; PEX: therapeutic plasma exchange; TMA: thrombotic microangiopathy; DIC: disseminated intravascular coagulation; MAHA: microangiopathic hemolytic anemia. * Diagnosis is based on the finding of MAHA and thrombocytopenia without another explanation. Neurologic findings may be present but are not seen in all patients; renal impairment is rare. We risk-stratify patients based on clinical criteria. ADAMTS13 activity testing should be performed as soon as possible, ideally before PEX is initiated; however, results may not be available for several days. Refer to UpToDate for details of the diagnostic evaluation, including the use of the PLASMIC score and other criteria that give high confidence in the diagnosis of TTP, which is based on clinical criteria rather than solely on ADAMTS13 activity. ¶ The following therapies are used in addition to PEX:
Glucocorticoids are given to all patients based on their potential to improve ADAMTS13 levels. Dosing is based on risk stratification (refer to inset box):
High-risk disease – Methylprednisolone 1000 mg intravenously per day for 3 days followed by prednisone 1 mg/kg daily orally.
Standard-risk disease – Prednisone 1 mg/kg per day orally.
Rituximab is used as part of initial therapy unless there is a contraindication. This is based on emerging evidence that rituximab may reduce the risks of exacerbation and relapse and may hasten the response to therapy.
Caplacizumab is given to those with high-risk disease to avoid potentially life-threatening complications.
Δ Response criteria are based on platelet count, with the exact details individualized according to the judgment of the treating clinician; refer to UpToDate for further discussion of these criteria. ◊ ADAMTS13 activity <10% is consistent with a diagnosis of TTP. Rarely, patients may have a slightly higher value; examples include an individual who has already undergone PEX before the blood sample was obtained. ADAMTS13 activity >20% is generally consistent with response to treatment or a condition other than TTP; in some cases, individuals with slightly lower values (in the range of 10 to 20%) may have a condition other than TTP. If an individual has an increase in platelet count and ADAMTS13 activity >10 to 20%, therapy is individualized based on the clinical distinction between resolving TTP and another resolving cause of thrombocytopenia. Refer to UpToDate for further discussion of ADAMTS13 testing, test interference, and interpretation. § Refer to UpToDate for options if TTP does not respond to PEX, high-dose glucocorticoids, rituximab, and caplacizumab.
