Three-year randomised study of high-purity or intermediate-purity factor VIII concentrates in symptom-free HIV-seropositive haemophiliacs: effects on immune status

Seremetis, Stephanie; Aledort, LM; Lau, Tty; Bergman, Garrett E.; Bona, Robert; Rickles, Frederick R.; Bray, Gordon L.; Kessler, Craig M.; Brettler, Doreen B.; Eyster, M. Elaine; Lusher, J.

doi:10.1016/0140-6736(93)91706-r

Cited by 79 publications

(62 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In the Seremetis et j al. [26] study, there was a high dropout rate, especially in the intermediate-purity arm. In a third randomized study by Mannucci et al [28], a high-purity (not monoclonal-antibody-purified) product was compared with an intermediate-1 purity product.…”

Section: In Vivo Propertiesmentioning

confidence: 99%

“…To sum up, there is some evidence that intermediate-pu rity concentrates have an impact on immune system varia bles, especially in vitro, and in several studies, treatment with monoclonal-antibody-purified concentrates in HIV-in fected individuals has been claimed to have a beneficial ef fect in terms of CD4 counts [26,27]. The studies are open to critisism, however, especially as the series are small, follow up times were restricted, and study designs not always well controlled, e.g.…”

Section: Immunomodulationmentioning

confidence: 99%

“…It has been claimed that highly purified concentrates, especially monoclonal antibody and recombinant products, are more inert vis-à-vis the immune system than less pure products. Two prospective randomized studies, one by Seremetis et al [26] and another by de Biasi et al [27], compari-! ng HIV-infected hemophiliacs treated with monoclonally purified products with those treated with intermediate-puri ty products, suggest that there is less rapid deterioration of CD4 cell counts in the groups treated with the purer prod ucts.…”

Section: In Vivo Propertiesmentioning

confidence: 99%

See 2 more Smart Citations

Why Prescribe Highly Purified Factor VIII and IX Concentrates?

Berntorp¹

1996

Vox Sanguinis

View full text Add to dashboard Cite

The aftermath of the HIV catastrophe and hepatitis virus transmission to hemophiliacs has been characterized by continuous efforts to improve the purity of factor VIII and factor IX concentrates, increasing sophistication of the virucidal methods used, and the introduction of recombinant factor VIII. The cost of hemophilia care is substantial and there is a large price difference between products depending on their purity; generally, the purer the concentrate, the higher the price. The use of expensive highly purified concentrates may be questioned if these products are not superior in terms of safety, efficacy or convenience. The properties of concentrates used in hemophilia care are discussed in this review, as are their safety and side effects. The available data do not clearly reveal any clinical difference between factor VIII concentrates, although the highly purified products may be of theoretical benefit. With regard to factor IX, purified products do not seem to carry any risk of the well-known thromboembolic complications which occur in certain situations after treatment with prothrombin complex concentrates.

show abstract

Section: In Vivo Propertiesmentioning

confidence: 99%

Section: Immunomodulationmentioning

confidence: 99%

Section: In Vivo Propertiesmentioning

confidence: 99%

See 1 more Smart Citation

Why Prescribe Highly Purified Factor VIII and IX Concentrates?

Berntorp¹

1996

Vox Sanguinis

View full text Add to dashboard Cite

show abstract

“…Recent studies have demonstrated that use of highly purified factor VIII concentrates seems to diminish the velocity of decay in numbers of CD4 cells in HIV-positive patients com pared to use of intermediately purified con centrates [83][84][85], Observant to these results, treatment strategies towards the HIV-infected hemophiliac have been influenced in many centers. However, it is unjustified to assume that the use of highly purified concentrates, per se, will be able to reduce or abolish the likelihood of AIDS in HIV-positive patients.…”

Section: Immunosuppressive Effects Of Plasma Derivativesmentioning

confidence: 99%

Safety of Plasma Derivatives

Ingerslev

1994

Pathophysiol Haemos Thromb

View full text Add to dashboard Cite

In clinical treatment practice of substitution therapy involving a plasma component, numerous aspects related to recipient’s safety are relevant to the physician. Since viral contaminants may be present in the donor blood, safety begins in the institution collecting raw plasma where donors are inquired about any unusual behavior that may potentially threaten safety. Other measures that could lead to exclusion of a donation are positive serological tests for HIV and hepatitis B and C. In this context, meticulously accurate logistics are mandatory. During the course of manufacture of plasma products, viral inactivation procedures have been adopted based on chemical and physical principles. The distinct effects of these depend on methodology and the types of virus in question. An important safety measure relates to establishing that the label value of content corresponds to the in vivo recovery of the reconstituted plasma derivative and, by inference, the clinical efficacy of the product. In patients deficient in plasma coagulation factors, treatment may trigger the development of functionally inhibiting alloantibodies against the factor needed for substitution which is a significant clinical complication. The reported incidences of such inhibitors have varied greatly. No clear relationship between their frequency and the type of concentrate used have been established. However, recent experience has shown an unexpected increase in inhibitors in a regional subset of previously stable patients when shifted from a dry-heat-inactivated concentrate to a pasteurized version of the same concentrate. Hence, the possible introduction of neoantigens is important. In the early era of concentrate use, side effects to treatment were often observed like alloimmune hemolytic anemia and various degrees of anaphylactoid reactions. With the appearance of concentrates of increased purity that contain less unwarranted proteins, side effects of this kind have been rare. In conclusion, safety of plasma derivatives by today’s standards is not a single entity, but a long chain of interdependent issues, each of which needs full attention to protect patients from mild and serious treatment complications.

show abstract

“…This issue might be important not only for the development of inhibitors, but also for replacement therapy in haemophiliacs with associated immune defects such as HIV. In this context, it is noteworthy that monoclonal antibody (Mab)-purified CFCs may stabilize the CD4 þ cell count in HIV-infected haemophiliacs, although it has not been possible to correlate this effect to improved clinical outcome (de Biasi et al, 1991;Goldsmith et al, 1991;Mannucci et al, 1992;Seremetis et al, 1993;Hilgartner et al, 1993).…”

mentioning

confidence: 99%

No effect of a new second‐generation B‐domain‐deleted recombinant product on lymphocyte transformation in vitro: a study of plasma‐derived and recombinant products

1997

View full text Add to dashboard Cite

Summary. Immunomodulatory effects of various factor VIII and factor IX clotting factor concentrates (CFCs) and of albumin were evaluated by a sensitive assay measuring the incorporation of 3 H-thymidine in phytohaemagglutinin-stimulated lymphocytes in the presence of monodansylthiacadaverine.In contrast to previous findings by others, we found lymphocyte transformation to be inhibited by all plasmaderived factor VIII concentrates at concentrations of 0 . 02, 0 . 2 and 2 . 0 IU/ml, including those purified by monoclonal antibodies (P < 0 . 05). Kryobulin TIM3 had the most pronounced effect. In addition, three plasma-derived human albumin preparations exerted a similar inhibitory effect as the factor VIII concentrates, whereas the corresponding plasma-derived factor IX concentrates only manifested minor immunomodulatory effects.Of the recombinant preparations, only Recombinate exerted an inhibitory effect at 0 . 02 and 0 . 2 IU/ml, whereas both Kogenate and Recombinate decreased 3 H-thymidine incorporation at 2 . 0 IU/ml (P ¼ 0 . 01). No immunomodulatory effect at all was observed with r-VIII SQ, a new B-domain-deleted recombinant factor VIII preparation free from added albumin. The significance of this finding regarding immunological side-effects including inhibitor development remains to be evaluated, but this second-generation recombinant product opens up new and interesting perspectives yet to be explored.

show abstract

Three-year randomised study of high-purity or intermediate-purity factor VIII concentrates in symptom-free HIV-seropositive haemophiliacs: effects on immune status

Cited by 79 publications

References 17 publications

Why Prescribe Highly Purified Factor VIII and IX Concentrates?

Why Prescribe Highly Purified Factor VIII and IX Concentrates?

Safety of Plasma Derivatives

No effect of a new second‐generation B‐domain‐deleted recombinant product on lymphocyte transformation in vitro: a study of plasma‐derived and recombinant products

Contact Info

Product

Resources

About