TTP/HUS Thrombotic Microangiopathy Management (ISTH 2024)

Algorithm Steps

1. ▶

   Start

   Suspected Thrombotic Microangiopathy (TMA)

   MAHA + thrombocytopenia

   1. ⚠

      Warning

      TMA Recognition

      Classic pentad (rarely complete)

      • CORE FEATURES:
      • 1. Microangiopathic hemolytic anemia (MAHA)
      • - Schistocytes on smear
      • - Elevated LDH
      • - Low haptoglobin
      • - Indirect hyperbilirubinemia
      • - Negative Coombs
      • 2. Thrombocytopenia
      • CLASSIC PENTAD (TTP):
      • - MAHA, Thrombocytopenia
      • - Fever, Neurologic changes, Renal dysfunction
      1. ●

         Action

         Initial Workup

         Confirm MAHA and rule out mimics

         • STAT LABS:
         • - CBC with smear (schistocytes)
         • - LDH, haptoglobin, indirect bilirubin
         • - Coombs (direct antiglobulin test)
         • - BMP, creatinine
         • - PT/INR, PTT, fibrinogen, D-dimer
         • - Pregnancy test
         • SEND:
         • - ADAMTS13 activity + inhibitor
         • - Complement (C3, C4)
         • - Stool culture/shiga toxin (if diarrhea)
         1. ●

            Action

            PLASMIC Score

            Predicts severe ADAMTS13 deficiency

            • 1 point each:
            • - Platelet count <30,000
            • - Hemolysis (retic >2.5%, haptoglobin undetectable, indirect bili >2)
            • - No active cancer
            • - No transplant history
            • - MCV <90 fL
            • - INR <1.5
            • - Creatinine <2.0
            • INTERPRETATION:
            • - 0-4: Low probability TTP
            • - 5: Intermediate
            • - 6-7: HIGH probability TTP
            1. ◆

               Decision

               Likely Etiology?

               Based on clinical picture

               1. ●

                  Action

                  TTP (Acquired or Congenital)

                  ADAMTS13 deficiency

                  • ADAMTS13 <10% confirms TTP
                  • Don't wait for results if high suspicion
                  • ACQUIRED TTP:
                  • - Autoantibody to ADAMTS13
                  • - More common
                  • CONGENITAL TTP (Upshaw-Schulman):
                  • - Inherited ADAMTS13 deficiency
                  • - Rare
                  1. ⚠

                     Warning

                     TTP Treatment

                     PLASMA EXCHANGE IS LIFESAVING

                     • PLASMA EXCHANGE (PLEX):
                     • - Start ASAP (don't wait for ADAMTS13)
                     • - 1-1.5 plasma volumes daily
                     • - Continue until platelets >150 x 2 days
                     • CORTICOSTEROIDS:
                     • - Methylprednisolone 1g IV x 3 days
                     • - Then prednisone 1 mg/kg
                     • CAPLACIZUMAB (anti-vWF):
                     • - 11 mg IV then 11 mg SC daily
                     • - Reduces time to remission
                     • RITUXIMAB:
                     • - For refractory/relapsing
                     • - 375 mg/m² weekly x 4
                     1. ●

                        Action

                        Monitoring

                        Track response to therapy

                        • DAILY:
                        • - Platelet count
                        • - LDH
                        • - Hemoglobin
                        • RESPONSE CRITERIA:
                        • - Platelets >150,000 x 2 days
                        • - Normalizing LDH
                        • - No new symptoms
                        • REFRACTORY:
                        • - No improvement after 3-5 PLEX
                        • - Add rituximab
                        1. ✓

                           Outcome

                           Outcomes

                           Prognosis

                           • TTP with PLEX: Survival >90%
                           • TTP without treatment: 90% mortality
                           • aHUS with eculizumab: Excellent renal outcomes
                           • STEC-HUS: Usually self-limited
                           • Relapse risk: 20-40% for TTP
               2. ●

                  Action

                  HUS

                  Typical (STEC) vs Atypical (aHUS)

                  • TYPICAL HUS (STEC-HUS):
                  • - Shiga toxin-producing E. coli
                  • - Bloody diarrhea prodrome
                  • - Children > adults
                  • - Supportive care, usually resolves
                  • ATYPICAL HUS (aHUS):
                  • - Complement dysregulation
                  • - No diarrhea prodrome
                  • - Renal failure prominent
                  • - Needs complement inhibitor
                  1. ●

                     Action

                     aHUS Treatment

                     Complement inhibition

                     • ECULIZUMAB:
                     • - Anti-C5 monoclonal antibody
                     • - 900 mg IV weekly x 4, then 1200 mg q2 weeks
                     • - Meningococcal vaccine REQUIRED
                     • RAVULIZUMAB:
                     • - Longer-acting C5 inhibitor
                     • - Less frequent dosing
                     • SUPPORTIVE:
                     • - Dialysis if needed
                     • - BP control
                     • - Avoid nephrotoxins
               3. ●

                  Action

                  Secondary TMA

                  Treat underlying cause

                  • CAUSES:
                  • - Drug-induced (quinine, gemcitabine, calcineurin inhibitors)
                  • - Malignant hypertension
                  • - Transplant-associated
                  • - Pregnancy (HELLP, preeclampsia)
                  • - Cancer-associated
                  • - Infection (HIV, COVID)
                  • TREATMENT: Address underlying cause