The novel plasma-derived FV concentrate was effective to correct "in vitro" severe FV deficiency in patients. The optimal FV concentration to fully normalize both global clotting times and thrombin generation parameters using the novel plasma-derived FV concentrate was 25 IU/dL.

Several highly purified products, suitable for haemophilia A and von Willebrand disease management, can be obtained, through the same chromatographic process, on an industrial scale.

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The von Willebrand ristocetin cofactor assay is still the main cleared measurement test used to evaluate von Willebrand factor (vWF) activity in concentrate samples containing vWF. Although the assay's performance has been improved over the years, the test reliability is still affected by a high interassay and interlaboratory variability; moreover, it requires skilled technicians and significant time. An automated HemosIL vWF:activity test, already set up on plasma samples, was then applied to factor VIII/vWF concentrates to verify its suitability in routine analysis of concentrate samples. As first step precision, linearity and accuracy were assessed. Then, 40 commercial batches of a high purity factor VIII/vWF concentrate were examined with this new method. The Spearman's correlation between the results obtained with the HemosIL vWF:activity assay and vWF activities determined by established procedures was evaluated. Comparisons of the means between HemosIL vWF:activity and the other tests were calculated with the Wilcoxon and Bland-Altman tests. Validation study showed satisfying within-run and between-run precision values. Activities determined with HemosIL vWF:activity had good correlation with those determined as ristocetin cofactor, Imubind (vWF:Imubind) and collagen-binding. Wilcoxon test, used to compare the means between the HemosIL vWF:activity and the other activity assessments, proved no significant variation with vWF:Imubind, but displayed a slight variation with von Willebrand ristocetin cofactor and von Willebrand factor:collagen-binding. This automated HemosIL vWF:activity test could be included in routine determination of vWF activity in concentrate samples and supports traditional von Willebrand ristocetin cofactor because it is reliable, reproducible and sensitive.

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We investigated and optimized a purification process, suitable for industrial scale, to obtain pharmaceutical grade apo-Tf (apo-transferrin), preserving its physiological properties and functions. Apo-Tf was obtained from fraction IV subfraction 1 and IV subfraction 4 (fraction IV-1,4), a waste product of the Cohn fractionation process, performing a single chromatographic run and two viral inactivation/removal steps. The structural integrity and the biological activity of the final product were extensively tested. The yield of apo-Tf produced was 80% on laboratory scale and 90% in scale-up lots, and the purity was higher than 95%. The purified protein preserves iron- and receptor-binding activities and shows a normal glycosylation pattern. The single chromatographic step process presented here provides an efficient means to prepare commercial quantities of the protein. The final product is sterile and two viral inactivation/removal steps were introduced into the process.

We are writing to share our data on a plasma-derived double−viralinactivated factor VIII (FVIII) concentrate (Antihaemophilic factor [Human]) in an effort to help patients with thrombotic thrombocytopenic purpura (TTP), a rare form of thrombotic microangiopathy associated with microangiopathic haemolytic anaemia and multiorgan dysfunction, typically involving the brain, kidneys, heart and gastrointestinal tract. 1,2 This condition is due to a deficiency of ADAMTS13, an enzyme responsible for the cleavage of ultra-large von Willebrand factor (VWF) multimers. 1,3 In the absence of functional ADAMTS13, ultra-large VWF multimers can accumulate and interact with platelets to produce occlusive microvascular thrombosis. 3 Thrombotic thrombocytopenic purpura can be congenital (hereditary) or mediated by an immune response (acquired) and can be fatal if not appropriately addressed. 1,2 ADAMTS13 replacement with fresh frozen plasma (FFP) for on-demand or prophylactic treatment is the standard of care for patients with congenital TTP. 4 Treatment of acquired TTP usually involves the infusion of FFP or exchange plasmapheresis in order to putatively remove anti-ADAMTS13 autoantibodies and replace functional ADAMTS13 in combination with corticosteroid therapy to suppress the immune response. 2,5 In both congenital and acquired TTP, allergic reactions, including anaphylaxis, as well as development of overload complications of FFP, present a therapeutic limitation of FFP administration. 4

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