Background
Randomized controlled trial. 102 patients with thrombotic thrombocytopenic purpura (TTP). Compared plasma exchange (PE) to plasma infusion (PI) as initial therapy. TTP is characterized by the pentad of thrombocytopenia, microangiopathic hemolytic anemia (MAHA), neurologic abnormalities, fever, and renal dysfunction. Prior to this trial, both PE and PI were used without head-to-head comparison. TTP pathophysiology involves deficiency of ADAMTS13 (a VWF-cleaving protease), leading to ultra-large VWF multimers that cause platelet aggregation and microvascular thrombosis. PE both removes anti-ADAMTS13 antibodies and replenishes ADAMTS13 activity; PI only replenishes ADAMTS13.
Interventions and follow up
Arm A: Plasma exchange (PE) — 1.5× plasma volume exchanged daily with fresh frozen plasma as replacement fluid
Arm B: Plasma infusion (PI) — 30 mL/kg/day of fresh frozen plasma
Primary endpoint: Response at 6 months (normal platelet count and LDH, absence of neurologic or renal abnormalities)
mFollow up: 6 month
Arm B: Plasma infusion (PI) — 30 mL/kg/day of fresh frozen plasma
Primary endpoint: Response at 6 months (normal platelet count and LDH, absence of neurologic or renal abnormalities)
mFollow up: 6 month
Results
Response at 6 months: 78% (PE) vs 51% (PI); P=.002
Early response at day 9: PE significantly superior (P=.033)
Survival at 6 months: 78% (PE) vs 63% (PI); P=.035
Time to response: Shorter with PE
Early response at day 9: PE significantly superior (P=.033)
Survival at 6 months: 78% (PE) vs 63% (PI); P=.035
Time to response: Shorter with PE
Adverse events
Main adverse events: Catheter-related complications with PE (central venous access required). Allergic reactions to FFP in both arms. Fluid overload risk with PI (volume limitations). Citrate toxicity with large-volume PE. Infection risk from central venous catheters. Cross-study use of steroids and antiplatelet agents not standardized.
Conclusions
Plasma exchange was superior to plasma infusion for response and survival in TTP, establishing daily PE as the cornerstone of initial TTP therapy and the standard of care for over two decades.
Key Limitations
Key Limitations: Relatively small trial (n=102). Steroid use was not standardized across patients. ADAMTS13 testing was not available — some patients may have had TMA of other etiologies (aHUS, drug-induced TMA). Modern TTP management also incorporates caplacizumab (TITAN, HERCULES trials) for adjunct von Willebrand factor inhibition. The optimal PE volume, endpoint of PE, and optimal plasma replacement fluid (FFP vs solvent-detergent plasma) have been refined in subsequent studies. Many patients required more than 1 PE course or had relapses.
Clinical Context
The Rock 1991 trial established daily plasma exchange as the foundational treatment for TTP. Modern TTP management builds on this: caplacizumab (anti-VWF nanobody) was added to PE + immunosuppression to accelerate platelet recovery and reduce TMA exacerbations (TITAN/HERCULES trials, both in this database). Rituximab is used for refractory/relapsing immune TTP to deplete anti-ADAMTS13 B-cell clones. ADAMTS13 activity <10% with inhibitor is now used to confirm immune TTP. Congenital TTP (Upshaw-Schulman, ADAMTS13 gene mutations) is treated with prophylactic plasma infusion without PE, as no antibody removal is needed.
References