Thrombotic Thrombocytopenic Purpura Management (ISTH 2025)

Algorithm Steps

1. ▶

   Start

   Suspected TTP

   MAHA + thrombocytopenia without alternative explanation

   1. ●

      Action

      Initial Evaluation

      Confirm microangiopathic hemolytic anemia

      • CBC with smear (schistocytes)
      • Reticulocyte count (elevated)
      • LDH (markedly elevated)
      • Haptoglobin (low/absent)
      • Indirect bilirubin (elevated)
      • Direct Coombs (negative)
      • Creatinine, troponin
      1. ●

         Action

         Calculate PLASMIC Score

         Predict likelihood of ADAMTS13 <10%

         • Platelet count <30 (+1)
         • Hemolysis (retic>2.5%, haptoglobin absent, indirect bili>2) (+1)
         • No active cancer (+1)
         • No stem cell/organ transplant (+1)
         • MCV <90 (+1)
         • INR <1.5 (+1)
         • Creatinine <2.0 (+1)
         1. ◆

            Decision

            PLASMIC Score Result

            Risk stratify for TTP

            1. ●

               Action

               Score 0-4: Low Risk

               Consider alternative diagnoses

               • HUS (especially if diarrhea, Shiga toxin)
               • Drug-induced TMA
               • DIC
               • Severe preeclampsia/HELLP
               • Still send ADAMTS13
            2. ●

               Action

               Score 5: Intermediate

               Clinical judgment required

               • Send ADAMTS13 urgently
               • Consider empiric TPE if high suspicion
               • Close monitoring
               1. ●

                  Action

                  Initiate TTP Treatment

                  Start immediately for high-risk patients

                  • Plasma exchange (TPE) - 1-1.5 plasma volumes daily
                  • Corticosteroids (methylpred 1g IV x3 days or pred 1mg/kg)
                  • Caplacizumab 11mg IV then 11mg SQ daily
                  • Send ADAMTS13 activity and inhibitor BEFORE TPE
                  • Avoid platelet transfusion unless life-threatening bleeding
                  1. ◆

                     Decision

                     ADAMTS13 Result

                     Confirms or excludes TTP

                     1. ●

                        Action

                        ADAMTS13 <10%: Confirmed iTTP

                        Continue full TTP therapy

                        • Continue daily TPE until plt >150 x2 days
                        • Continue caplacizumab 30 days post-TPE
                        • Rituximab 375mg/m² weekly x4 if inhibitor present
                        • Taper steroids over weeks
                        • Monitor for relapse (ADAMTS13 q1-3 months)
                        1. ✓

                           Outcome

                           TTP Remission

                           Platelets normalized, ADAMTS13 recovering

                        2. ✓

                           Outcome

                           Refractory TTP

                           Consider twice-daily TPE, splenectomy, or N-acetylcysteine

                     2. ●

                        Action

                        ADAMTS13 >20%: Not TTP

                        Pursue alternative diagnosis

                        • Stop TPE if started empirically
                        • Consider: aHUS, drug-TMA, malignancy-associated
                        • For aHUS: complement testing, eculizumab
                        • Hematology consultation
            3. ⚠

               Warning

               Score 6-7: High Risk

               Treat as TTP - do not wait for ADAMTS13