A total of three studies (one hemovigilance study, one prospective cohort, one retrospective cohort) that represented a total of 1,304 patients in addition to a total of 941 transfusion reaction reports were included in this systematic review update. A discussion of laboratory, clinical, and safety measures is provided in section 5.1 below. The three clinical studies included reported on the use of Octaplas in a variety of clinical conditions. In one of these studies, Octaplas was used to treat acute TTP, while it was used to treat a variety of bleeding disorders in the other two studies.

Overall, our findings add little to our 2007 conclusion suggesting that Octaplas is effective in improving clinical outcomes, in bleeding disorders. Based on this systematic review update, Octaplas may be comparable with FFP in terms of treatment response and volume needed to treat acute TTP. There are still no adequately powered RCTs comparing Octaplas with other replacement fluids as the initial treatment for TTP. Our findings suggest that Octaplas may result in fewer adverse reactions, as compared with CPP in patients with acute TTP, and as compared with FFP or FP in treatment or prevention of bleeding. However, these results are based only on observational studies. No randomized trials are available to evaluate either the clinical effectiveness or the safety of Octaplas. Given the paucity of rigorous research evaluating the effectiveness of Octaplas as a substitute for FP, firm conclusions are not possible. This lack of evidence is illustrated by the persistent lack of randomized trials, as well as the overall poor quality and quantity of the included studies. All three observational studies had at least one deficiency, as determined by a predetermined set of key methodological quality criteria (Table 2).

5.1. Summary of Results

None of the three observational studies included in this review reported findings regarding levels of coagulation proteins in patients receiving Octaplas, but some clinical data were reported on clinical evolution and safety. However, important outcomes remain inadequately studied in the studies included. Bleeding outcomes such as hemostatic effectiveness were not evaluated. In addition, none of the included studies used a standardized or validated tool to evaluate bleeding.

The only study that focused on a particular condition relates to acute TTP.2 Response rate was similar between Octaplas and CPP, but there were two to three times fewer allergic or citrate reactions with Octaplas than with CPP, which was highly statistically significant. Other safety outcomes were similar between study groups (no HAV/HBV/HCV/HIV seroconversion, no TRALI, no death). The study size was small (32 patients, 50 transfusions), with a retrospective design. As a result, no definitive conclusions can be reached about either the effectiveness or the potential adverse effects of using Octaplas as an initial replacement fluid for plasma exchange in patients with TTP.

The other two studies were larger (hundreds of transfusions each), with prospective controlled designs and a focus on safety. The superior safety profile of Octaplas over FFP or wet plasma showed by a single-centre study conducted in Sweden over two years (zero adverse reactions reported)1 was also observed in a comparison of hemovigilance data from Norway and four other European countries (almost twice less serious immunologic reactions and no TRALI).3

From the identified studies, there is still a gap in current research with regard to important clinical and laboratory outcomes. While Octaplas and FFP may produce similar results in terms of changes in safety outcomes, there are differences in the composition of the products that may lead to some differences in laboratory outcomes. Based on the current evidence available, it is not possible to ascertain whether there are differences in clinically important outcomes such as bleeding, thrombosis, infections, or other transfusion reactions. Further research directly comparing FFP and Octaplas in RCTs is required to determine whether there are any clinically important differences associated with the use of Octaplas and FFP.

5.2. Study Limitations

Limitations associated with this systematic review update were noted during compilation of the evidence pertaining to the effectiveness and safety of Octaplas. First, limited information in terms of clinical indications, treatment regimens employed, outcomes reported, and approach to outcome reporting made meta-analysis of study-specific findings infeasible. As mentioned above, the quality of the published reports was poor, seriously limiting the strength of the conclusions that can be derived from the included studies. This was additionally compounded by the fact that the study designs used were hypothesis generating in nature. In addition, a viable assessment of publication bias using funnel plots was not performed, given that meta-analysis was not feasible in this systematic review, and one cannot rule out the possibility that there exist unpublished studies that may alter the conclusions of this systematic review. Lastly, in both our original review (2007) and this update, we excluded studies that tested S/D plasma products other than Octaplas. As such, this report is not a review of S/D products, but specifically Octaplas. As noted in the original report, other S/D plasmas are prepared using similar processes but there can be differences in the final products. Including the studies of other S/D plasma products might better characterize current evidence for S/D plasma, but this is unlikely, given the small number of studies examining other S/D products identified in our literature searches.

5.3. Generalizability of Findings

A number of factors limit the generalizability of the findings in this systematic review. The included studies evaluated Octaplas in patients with a variety of disorders, including patients with TTP, patients requiring intensive care, patients with thorax conditions, and patients with other unspecified bleeding disorders. The one TTP-specific study was small and retrospective, and the two larger prospective studies had mixed populations, with no subgroup analysis focusing on specific conditions. Even for the patient groups identified in the studies, the lack of RCTs testing Octaplas versus FFP limits the generalizability of any comparisons between Octaplas and FFP. For important indications such as TTP, cardiac surgery, and other surgeries, there is no evidence from RCTs comparing Octaplas and FFP. As a result, any generalization of the results from the individual studies and this systematic review must be tempered with caution.

5.4. Health Services Impact

The impact on health services of the use of Octaplas instead of FFP is difficult to assess, given the limited evidence available. Based on the included studies, the effectiveness of Octaplas as compared with FFP cannot be adequately assessed to determine whether there are any differences in clinical effectiveness or adverse events. Further research comparing Octaplas and FFP is required to determine the potential impact of Octaplas on health services.

5.5. Knowledge Gaps

From the included studies, there are important knowledge gaps in the current evidence. As discussed previously, the lack of direct comparison between Octaplas and FFP in RCTs limits the ability to compare the effectiveness and safety of Octaplas and FFP. Important clinical outcomes have also not been adequately addressed, including the number of patients who have correction of their coagulation parameters (INR, aPTT, PT), bleeding outcomes, and adverse transfusion reactions.