Cryoprecipitate-Poor Plasma Instead of Fresh Frozen Plasma As Replacement Therapy in Thrombotic Thrombocytopenic Purpura: A Systematic Review and Meta-Analysis

Background: Thrombotic thrombocytopenic purpura (TTP) is a life-threatening condition characterized by the presence of small-vessel thrombi enriched with platelets, leading to thrombocytopenia, thrombotic microangiopathy (TMA), and on occasion, resulting in end-organ damage. The standard therapeutic plasma exchange (TPE) approach, initiated after suspicion of TTP, is done with fresh frozen plasma (FFP). Yet, the use of cryoprecipitate-poor plasma (CPP) has been suggested as alternative in recent decades given its absence of von Willebrand factor, which would benefit the pathophysiology of TTP. However, its efficacy over FFP remains unclear. Therefore, we aimed to conduct a meta-analysis to compare the safety and efficacy of CPP versus FFP in patients with TTP.

Methods: We systematically searched PubMed, Cochrane Central and Embase for clinical studies published up to June 2023, comparing CPP to FFP as replacement fluids in TPP or TMA patients. Outcomes assessed were overall mortality, relapse rate, response to treatment and number of TPE sessions. We pooled outcomes as odds ratios (OR) and mean differences (MD) with 95% confidence intervals (CI). We also performed a subgroup analysis with randomized controlled trials (RCTs). Statistical analysis was performed with Review Manager version 5.4.1. Heterogeneity was assessed with I ² statistics. The protocol was registered in PROSPERO (ID: CRD42023440665).

Results: A total of eight articles met inclusion criteria, of which three were RCTs. The combined dataset involved 290 patients, of which 144 (49.7%) were in CPP group and 146 (50.3%) in the FFP group. CPP significantly reduced overall mortality compared to FFP (OR 0.27; 95% CI 0.13-0.59; p=0.001; I ²=0%; Figure 1A). However, our subgroup analysis of RCTs showed no significant difference in overall mortality between groups (OR 0.49; 95% CI 0.13-1.84; p=0.29; I ²=0%; Figure 1B). Additionally, there were no significant differences between groups regarding relapses (OR 0.81; 95% CI 0.37-1.77; p=0.60; I ²=0%; Figure 1C), response to treatment (OR 2.20; 95% CI 0.69-7.07; p=0.18; I ²=44%; Figure 1D) or number of TPE sessions (MD 1.63; 95% CI -2.83 - 6.08; p=0.47; I ²=55%; Figure 1E).

Conclusion: Our meta-analysis shows that the safety and efficacy of CPP in TTP patients is at least similar to FFP in reducing mortality, relapse rate, and improving response to treatment. The reduced mortality with CPP found in the whole pool of studies, along with the trend towards reduced mortality found in the RCT-only analysis indicates the potential benefit of CPP over FFP. However, larger population-based randomized trials should contribute to narrow confidence intervals and decrease bias of observational studies, providing clearer conclusions for treatment efficacy in the future.