Coagulation Factors in Therapeutic Apheresis Plasma Held for 18 Hours at Ambient Temperature Prior to Pathogen Inactivation (INTERCEPT™).

Background. A photochemical treatment (PCT) using amotosalen HCl (S-59) and UVA light inactivates pathogens and leukocytes in therapeutic single donor apheresis fresh frozen plasma (INTERCEPT™, I-FFP) prepared within 8 hr of collection. Previous studies demonstrated a broad spectrum of pathogen inactivation (

Aims. We measured coagulation factors in apheresis plasma stored for 18 hr at ambient temperature, processed with pathogen inactivation, and frozen.

Methods. Fifteen jumbo plasma units (650 mL), were collected by apheresis with AB16 anticoagulant from group A, B, AB and O donors (MCS+. Haemonetics, Braintree, MA). Plasma collections were held at ambient blood bank temperature (20 – 24 °C) prior to further processing. After 18 hr, baseline samples for assay of coagulation factors were withdrawn before PCT. Plasma (635 mL plasma) was mixed with 15 mL of 6 mM amotosalen (150 uM: final concentration) and illuminated with a 3 J/cm² UVA treatment. Following illumination (~ 8 min) and passage through a flow compound adsorption device (~20 min) to reduce levels of residual S-59, treated plasma units (650 mL) were divided into 3 equal storage units of ≥ 200 mL. Before freezing, post-treatment samples were withdrawn for factor assays. Treated plasma units were flash frozen at −80°C, and transferred to −30°C for 12-month storage. Plasma units were withdrawn to measure total protein, albumin, IgG, IgM, IgA, fibrinogen, factors II, V, VII, VIII, IX, X, XI, XII, VIII-vWF, Proteins C and S, AT III, plasminogen, alpha-2 antiplasmin, D-dimers, PT, and APTT.

Results. Baseline coagulation factor levels (Mean ± SD) were in therapeutic ranges after 18 hr storage at ambient temperature. After PCT, all units had residual platelets < 1x10⁹/L, WBC < 1x10⁴/L, and RBC < 1 x 10⁹/L. After PCT, total protein (59 ± 4 g/L), albumin (38 ± 2 g/L), IgG (9.0 ± 1.7g/L), IgA (1.6 ± 0.8 g/L) and IgM (0.9 ± 0.5 g/L) were unchanged from baseline. Mean values for fibrinogen (g/L), coagulation factors (IU/dL), coagulation inhibitors (IU/dL) were variably reduced from baseline, but within the ranges defined for therapeutic plasma (Table). Treated plasma showed no evidence of activation.

Conclusions. Apheresis plasma held for 18 hr before processing with the INTERCEPT system for pathogen inactivation retained coagulation factor activity levels in conformance with French national standards for therapeutic frozen plasma (FP). Approximately 36 units (200 mL) could be prepared per hr with this system. A single UVA platform is compatible with the operational requirements of a regional blood center producing 12,000 doses (200 mL) of therapeutic FP and 12,000 doses of platelets per year.

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