Management of Thrombotic Thrombocytopenic Purpura (TTP)

Immediate Recognition and Stabilization

The American College of Physicians recommends immediate initiation of therapeutic plasma exchange (TPE) combined with corticosteroids and rituximab as soon as TTP is suspected, as delay in treatment significantly increases mortality 1
Rapid recognition and immediate hematology consultation are crucial, as delays directly correlate with increased morbidity and mortality 1

A peripheral blood smear should be performed to confirm schistocytes, which is critical for diagnosis 1
ADAMTS13 activity level and inhibitor titer should be measured, although treatment should not be delayed awaiting results 1
Laboratory markers such as LDH, haptoglobin, reticulocyte count, bilirubin, and urinalysis should be assessed 1
Coagulation studies, including PT, aPTT, and fibrinogen, should be performed 1
Blood type and antibody screen, direct antiglobulin test, and drug exposure history should be evaluated 1

The American Society of Hematology recommends administering methylprednisolone 1 g IV daily for 3 days, with the first dose given immediately after the first TPE session 1
Following initial high-dose therapy, transition to prednisone 1-2 mg/kg/day 1
Rituximab should be offered as part of initial therapy for acquired TTP 1
Complete the full course of rituximab if initiated 1

Caplacizumab should be considered for patients with severe ADAMTS13 deficiency, particularly if ADAMTS13 activity is severely reduced with elevated inhibitor or anti-ADAMTS13 IgG 1
Discontinue caplacizumab if no exacerbation occurs within 3-5 days after stopping TPE 1

Platelet transfusions should be avoided unless life-threatening hemorrhage occurs, as they may worsen thrombosis 1
RBC transfusion should be transfused only the minimum necessary to relieve symptoms or achieve hemoglobin 7-8 g/dL in stable patients 1
Coordinate with blood bank before any transfusions 1
Daily assessment of platelet count, hemoglobin, LDH, and clinical status during active TPE should be performed 1
Weekly monitoring of hemoglobin levels until steroid taper is complete should be done 1

Additional immunosuppression, such as cyclosporine, cyclophosphamide, vincristine, mycophenolate mofetil, or anti-thymocyte globulin, may be considered for patients not responding to standard therapy or presenting with life-threatening complications 1

The Kidney International guideline recommends using the PLASMIC score to risk-stratify patients, with a score ≥5 points indicating intermediate-to-high risk and warranting immediate treatment in adults 2
In patients with systemic lupus erythematosus presenting with thrombotic microangiopathy, TTP should be considered and ADAMTS13 testing performed, with comanagement with an experienced hematologist preferable when expertise is available 2
The PLASMIC score can be used to distinguish TTP from other conditions, such as antiphospholipid syndrome-related TMA and complement-mediated TMA, in patients with systemic lupus erythematosus 2

In acquired thrombotic thrombocytopenic purpura, roughly 40 % of patients do not demonstrate clinical or laboratory improvement during the first 4 weeks of therapy, but this early lack of response does not necessarily mean the treatment is ineffective or that outcomes will be worse. 3