Distinguishing and Managing TTP, HUS, and MAHA

Diagnostic Approach

The American College of Cardiology recommends urgent ADAMTS13 activity testing to differentiate TTP, HUS, and MAHA, with severely deficient activity (<10%) indicating TTP, which requires immediate plasma exchange initiation 1, 2
Initial laboratory evaluation should include peripheral blood smear for schistocytes, ADAMTS13 activity level and inhibitor titer, complete blood count, LDH, haptoglobin, reticulocyte count, indirect bilirubin, serum creatinine, direct antiglobulin test, and stool studies for Shiga toxin/E. coli O157:H7 if diarrhea is present 1, 2, 3, 4, 5, 6, 7, 8
The PLASMIC score can be used for risk stratification in suspected TTP when ADAMTS13 results are pending, with intermediate-to-high risk in adults requiring immediate plasma exchange initiation 2, 9

For TTP, the American Society of Hematology recommends prednisone 0.5-1 mg/kg/day, hematology consultation, and holding immune checkpoint inhibitors, with permanent discontinuation in severe cases 1, 5
For atypical HUS, the European Renal Association recommends eculizumab therapy, with a dosing regimen of 900 mg weekly for 4 doses, then 1200 mg at week 5, and 1200 mg every 2 weeks thereafter 6, 8
For MAHA, treatment is focused on addressing the underlying cause, with supportive care and monitoring of laboratory parameters such as hemoglobin, platelet count, LDH, and haptoglobin 4, 6

Weekly hemoglobin levels during steroid taper, then less frequently, to monitor treatment response 5, 6
Platelet counts, LDH, and haptoglobin to assess treatment response and detect potential complications 4, 6

Platelet transfusion is contraindicated in TTP unless life-threatening bleeding occurs, as it may worsen thrombosis 6
Drug-induced TMA can occur with certain medications, such as chemotherapy, tacrolimus, cyclosporine, sirolimus, quinine, and antibiotics, and a detailed medication history is essential 1, 5

The risk of hemorrhage from a percutaneous kidney biopsy rises markedly when platelet counts are below 50 × 10³/µL, making thrombocytopenic patients especially vulnerable. 10
Platelet transfusion before invasive procedures should be reserved for situations of life‑threatening bleeding; routine prophylactic transfusion in severe thrombocytopenia is not recommended. 11

A platelet count of at least 50 × 10³/µL (preferably >100 × 10³/µL) should be confirmed prior to attempting a renal biopsy. 10
Coagulation studies must show normal prothrombin time (PT) and activated partial thromboplastin time (aPTT), and bleeding time should be ≤10–15 minutes. 10

Kidney biopsy can be considered once the acute thrombotic microangiopathy episode is controlled with plasma exchange and the platelet count has recovered to ≥50 × 10³/µL; many experts suggest waiting until counts exceed 150 × 10³/µL for added safety. [11][10]

In patients with underlying systemic lupus erythematosus, performing a biopsy after hemodynamic stabilization helps differentiate primary lupus nephritis from TMA, which guides long‑term immunosuppressive therapy. 12
When the clinical response to initial plasma exchange is atypical or incomplete, or when alternative renal pathologies (e.g., lupus nephritis, complement‑mediated HUS) are suspected, a delayed biopsy provides definitive histologic clarification. 12