Factor VIII manufactured from plasma—the ups and downs, and the up again: a personal journey—part 1: history of the development of plasma-derived factor VIII therapies

The discovery of cryoprecipitate as a modality for hemophilia A: Augmenting the allocation of credit

“…In addition, Pool's proximity to the plasma fractionation industry in the United States allowed her, together with her colleagues including EJ Hershgold, to rapidly develop potent lyophilized concentrates of Factor VIII using cryoprecipitate as starting material. As we have previously reported, 3,4 we would encourage similar recognition of the work of the French physician and hematologist Emile Rémigy, who characterized cryoprecipitate and used it to treat hemophilia A 10 years before Pool published her seminal work. Rémigy's work was published as a PhD thesis toward a Doctor of Medicine degree from the Faculty of Medicine in the University of Nancy in 1955 (Figure 1), and its publication in French, followed by Rémigy's death in a railroad accident in 1961, 5 precluded its recognition.…”

The legacy of haemophilia: Memories and reflections from three survivors

“…This was underpinned by an improved understanding of the stability of FVIII in plasma and during manufacture. 31,32 The manufacture of concentrates of Factor IX (FIX) also progressed rapidly, with the development of ion-exchange processes also able to extract FIX from the plasma after cryoprecipitate removal, again without hindering further fractionation. [33][34][35] The The amount of FVIII (10 6 units) supplied from National Health Service (domestic fractionation of plasma collected in the UK) and Commercially sourced plasma products is shown.…”

“…The preparation of cryoprecipitate as the preliminary fraction for FVIII manufacture allowed FVIII purification while not hindering the further fractionation of the residual plasma to other fractions such as albumin. This was underpinned by an improved understanding of the stability of FVIII in plasma and during manufacture 31,32 . The manufacture of concentrates of Factor IX (FIX) also progressed rapidly, with the development of ion‐exchange processes also able to extract FIX from the plasma after cryoprecipitate removal, again without hindering further fractionation 33–35 .…”