Transmission of Non-A, Non-B Hepatitis by Heat-Treated Factor Viii Concentrate

Evidence for transmission of non-A non-B hepatitis (NANB) was sought in 41 patients with primary immune deficiency who were receiving human intravenous immune globulin (IGIV) over periods ranging from 6 to 15 months at a monthly dosage of 400 mg/kg body weight. One lot of a reduced and alkylated IGIV and three lots of a nonmodified preparation stabilized at pH 4.2 were used. No evidence of NANB was found, although transient elevations in serum glutamic pyruvic transaminase (alanine aminotransferase) were found in 6 of the patients. The possible causes of the elevated levels in these 6 patients are discussed.

Section: Definition Of Nanbmentioning

confidence: 99%

Section: Definition Of Nanbmentioning

confidence: 99%

Non-A Non-B Hepatitis and the Safety of Intravenous Immune Globulin, pH 4.2: A Retrospective Survey

Rousell¹,

Good²,

Pirofsky³

et al. 1988

“…Studies have shown the high incidence of non-A, non-B hepatitis (NANBH) in patients receiving such concentrates for the first time [1,2], and other reports document the transmission of hepatitis B [3] and HIV [4], Heat treatment is an effective means of inactivation of many viruses and can be applied to the lyophilised product. However, experi ence with dry heated factor VIII concentrates suggests that transmission of NANBH is not eliminated by heating for 72 h at 60°C [5] and that, despite the fact that HIV has been shown to be rapidly inactivated at 60 °C in some circum stances [6], patients receiving at least one factor VIII con centrate heated in the lyophilised state for 30 h at 60 °C have seroconverted [7]. Thus, heating at higher temper atures or for longer periods may be required to inactivate NANBH and HIV viruses.…”

Section: Introductionmentioning

confidence: 98%

Severely Heated Therapeutic Factor Vili Concentrate of High Specific Activity

Winkelman¹,

Owen²,

Evans³

et al. 1989

A new method for the manufacture of a heated factor VIII concentrate of high specific activity (2-6 IU factor VIII:C/mg protein) has been developed. Addition of heparin to cryoprecipitate extract at acid pH precipitated fibrinogen and fibronectin. Factor VIII was then recovered from the supernatant by precipitation with glycine and sodium chloride. After re-solution and desalting on Sephadex G-25, the concentrate was sterile-filtered and lyophilised. The dried product was stable to heating in the final container at 80°C for 72 h. Data from 25 consecutive batches of concentrate prepared from 1,200-1,500 kg plasma pools are presented. The mean final yield of heated product was 190 IU factor VIII:C/kg plasma. The concentrate has been found to be safe and effective in clinical use.

“…Pas teurization of AHF under a variety of conditions has led to mixed results with regard to virus safety [18][19][20][21][22][23][24] and has led to alteration of protein structure [25]. Tri(nbutyl)phosphate (TN BP)/detergent mixtures appear to be both virucidal and specific [17,26]; however, transmis sion studies in man have just begun.…”

Section: Introductionmentioning

confidence: 99%

Inactivation of Lipid-Enveloped Viruses in Labile Blood Derivatives by Unsaturated Fatty Acids

Horowitz¹,

Piët²,

Prince³

et al. 1988

Virus sterilization of blood plasma derivatives by addition of several naturally occurring fatty acids was evaluated using vesicular stomatitis virus and Sindbis virus as markers for lipid-enveloped virus inactivation and human immunodeficiency virus (HIV). Inactivation of ≥10^4 tissue culture infectious doses (TCID(50)) of marker viruses added to antihemophilic factor (AHF) concentrates, with 60-100% retention of AHF activity, was achieved with oleic, 1l-eicosenoic, linoleic, linolenic, palmitoleic and arachidonic acids. Elaidic, gamma-linolenic, palmitic, and arachidic acids and another fat-soluble compound previously reported to inactivate virus, butylated hydroxytoluene. were less effective. A long chain mono- but not a di- or triglyceride also displayed virucidal properties. Evaluation of the inactivation of HIV added to an immune globulin solution on exposure to 0.033% sodium oleate for 20 min indicated inactivation of ≥10^3,4 TCID(50). The degree of virus inactivation depended on the sample composition. A favorable balance was achieved between degree of virus inactivation and retention of protein function for AHF concentrate, prothrombin complex concentrate, antithrombin III concentrate, and immune globulin solution on incubation with 0.033% (w/v) sodium oleate at 24 °C for 4-6 h. Virus inactivation in whole plasma and plasma cryoprecipitate was not complete despite use of higher concentrations of sodium oleate and/or incubation at 37 °C. Reduced virus kill in these less purified derivatives probably is a consequence of their endogenous lipid and/or albumin.