A minipool process for solvent–detergent treatment of cryoprecipitate at blood centres using a disposable bag system

Abstract

Viral inactivation treatment by TnBP, with or without Triton X-45, can be applied to minipools of cryoprecipitate, with good recovery of FVIII, VWF and fibrinogen. The viral inactivation and solvent-detergent removal process can be performed in a closed bag system and using simple blood establishment techniques and equipment. This technology could be considered for the improved viral safety of cryoprecipitate which is used to treat haemophilia A, von Willebrand disease or fibrinogen deficiency, or to prepare fibrin sealant.

Properties of a concentrated minipool solvent‐detergent treated cryoprecipitate processed in single‐use bag systems

“…The cryoprecipitate was re‐suspended using a minimal volume (8 mL) of a glucose/saline solution, which was selected since it is readily available worldwide as a pharmaceutical‐grade solution. The resuspended cryoprecipitate was then further processed into the S/D‐treatment bag [11]. Our objective was twofold: first, to increase the concentration of the three major therapeutic proteins of cryoprecipitate (FVIII, VWF and fibrinogen) so that lower injection volumes could be infused for the treatment of patients.…”

“…In the initial description of the minipool S/D technology [11], a standard production process was used to prepare the cryoprecipitate, leaving a relatively large volume of cryo‐poor plasma (ca. 15–20 mL) to ensure its re‐suspension.…”

Cryoprecipitate transfusion: current perspectives

“…8,27 The development of blood programs strengthening both blood availability and safety is a real need worldwide. 41 In countries where cryoprecipitate is the only available option, improving safety becomes paramount, and treatments using solvent/detergent, [42][43][44] which do not reduce hemostatic potency, are options that must be considered. …”

The Simultaneous Human FVIII/vWF Purification and Virus Inactivation Combined in Chromatographic Column

“…The incubation time was depending from virus type, R/D concentration and detergent nature and can continue from 2-5 min [9] to 6-24 hrs [9,10] to achieve a satisfied virus reduction. Normally the temperature of the treatment process was limited by the fast FVIII denaturation and did not exceed 30 [2][3][4][5], less often 2-8 [1,3,10] or 37˚C [6][7][8][9][10].…”

“…This method includes following S/D combinations: tri-n-butyl (TnBP) or di-n-propyl (DnPP) phosphates, or octoxynol and polysorbates (Tweens) 20/80 or Tritons (X-45 or X-100) or sodium cholate/ desoxycholate [1][2][3][4][5][6][7][8]. The S/D concentration was the most critical parameter, typically 0.3% solvent and 1% detergent, most frequently 1% [6], less often 0.3% and 0.2%, respectively [7,8]. A concentration as low as 0.15% TnBP/0.5% Triton X-100 was still completely effective, but an extended incubation period was required [3].…”