Effects of pathogen reduction technology and storage duration on the ability of cryoprecipitate to rescue induced coagulopathies in vitro

Abstract

Background Fibrinogen concentrates and cryoprecipitate are currently used for fibrinogen supplementation in bleeding patients with dysfibrinogenemia. Both products provide an abundant source of fibrinogen but take greater than 10 min to prepare for administration. Fibrinogen concentrates lack coagulation factors (i.e., factor VIII [FVIII], factor XIII [FXIII], von Willebrand factor [VWF]) important for robust hemostatic function. Cryoprecipitate products contain these factors but have short shelf lives (<6 h). Pathogen reduction (PR) of cryoprecipitate would provide a shelf‐stable immediately available adjunct containing factors important for rescuing hemostatic dysfunction. Study Design and Methods Hemostatic adjunct study products were psoralen‐treated PR‐cryoprecipitated fibrinogen complex (PR‐Cryo FC), cryoprecipitate (Cryo), and fibrinogen concentrates (FibCon). PR‐Cryo FC and Cryo were stored for 10 days at 20–24°C. Adjuncts were added to coagulopathies (dilutional, 3:7 whole blood [WB]:normal saline; or lytic, WB + 75 ng/ml tissue plasminogen activator), and hemostatic function was assessed by rotational thromboelastometry and thrombin generation. Results PR of cryoprecipitate did not reduce levels of FVIII, FXIII, or VWF. PR‐Cryo FC rescued dilutional coagulopathy similarly to Cryo, while generating significantly more thrombin than FibCon, which also rescued dilutional coagulopathy. Storage out to 10 days at 20–24°C did not diminish the hemostatic function of PR‐Cryo FC. Discussion PR‐Cryo FC provides similar and/or improved hemostatic rescue compared to FibCon in dilutional coagulopathies, and this rescue ability is stable over 10 days of storage. In hemorrhaging patients, where every minute delay is associated with a 5% increase in mortality, the immediate availability of PR‐Cryo FC has the potential to improve outcomes.

Preparation and Storage of Cryoprecipitate Derived from Amotosalen and UVA-Treated Apheresis Plasma and Assessment of In Vitro Quality Parameters

“…This is in contrast to our results of PR-Cryo, where we saw moderate but significant reductions after 120 h at RT in FVIII, Fb and vWF contents, respectively, but the European requirements were fulfilled. Our global coagulation results based on thrombolastography and thrombin generation show stable coagulation and no significant loss up to 120 h, as described in recent literature [16,17].…”

“…Moreover, Cushing et al showed that PR cryoprecipitate could be stored at ambient temperature for up to five days without losing clotting-factor levels or fibrin clot strength [ 15 ]. A similar study of Thomas et al proved the ability of PR-Cryo to rescue dilutional and lytical coagulopathy in comparison with fibrinogen concentrates and non-PR-Cryo in an in vitro study with a storage time of even 10 days at room temperature [ 16 ].…”

Factor VIII: A Dynamic Modulator of Hemostasis and Thrombosis in Trauma

“…Another in vitro study utilized a 3:7 ratio of whole blood/saline mixture, and tested pathogen-reduced CP (PR-CP; Cerus), standard CP, and hFC. 73 In this model, FVIII, FXIII, and VWF were not decreased in PR-CP compared to CP, and PR-CP and CP were more efficacious than hFC in restoring TF-activated EXTEM-CT and thrombin generation. PR-CP was reported to be stable in fibrinogen, FVIII/VWF, and FXIII content for 10 days at 20°C-24°C, which makes it a rapidly available alternative to CP and hFC.…”

Platelet dysfunction after trauma: From mechanisms to targeted treatment

“…Cryoprecipitate also contains other pro-hemostatic factors, such as FXIII, FVIII and VWF, and is associated with superior clotting kinetics in vitro. 137,138 In vitro data suggest that cryoprecipitate increases thrombin generation. 137 More data is necessary to evaluate to role of fibrinogen concentrate and cryoprecipitate on platelet dysfunction.…”

“…The mechanism by which fibrinogen improves outcomes could be, in part, due to promoting platelet adhesion and aggregation. Cryoprecipitate also contains other pro‐hemostatic factors, such as FXIII, FVIII and VWF, and is associated with superior clotting kinetics in vitro 137,138 . In vitro data suggest that cryoprecipitate increases thrombin generation 137 .…”