Inhibition of Human T Lymphocyte Proliferation in vitro by
Commercial Factor VIII Concentrates

Wang, Y.; Beck, Eugene A.; Furlan, M.; Weck, A.L. de

doi:10.1159/000465787

Cited by 3 publications

(4 citation statements)

References 6 publications

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“…Con A, or PWM, the factor VIII concentrate caused a decrease in the proliferative response (table III). This is consistent with other data reported in the literature [11]. However, the concentra tion of factor VIII required to inhibit blastogenesis by more than 50% was 2.7 U/ml which is at least 10-fold higher than the concentrations required to induce proli feration in a 7-day antigen-dependent-type assay.…”

Section: Resultssupporting

confidence: 92%

“…There is no evidence for a direct mitogenic effect (table III). Con sistent with other publications [11], the factor VIII prod uct was inhibitory to T cell mitogenesis. The in vivo relevance of the inhibitory effect on mitogenesis is not obvious, as the concentration of factor VIII required to induce a significant (3=50%) inhibition is rarely reached during therapy as plasma levels after infusions typically Normal PBMC were incubated with mitogen and factor VIII product for 3 days and assessed for proliferation by tntiated thymid ine uptake.…”

Section: Resultssupporting

confidence: 83%

“…Background prolifera tion (without factor VIII or lectins) was 0.4 and 0.3x103cpm in experiments 1 and 2. reach 0.4 U/ml. Similarly Wang et al [ 11 ] required factor VIII levels of 1.0-2.4 U/ml to achieve significant inhibi tion of proliferation.…”

Section: Resultsmentioning

confidence: 96%

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T Lymphocytes from Hemophiliacs Proliferate after Exposure to Factor VIII Product

Matheson¹,

Green²,

Poon³

et al. 1986

Vox Sanguinis

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Chronic exposure of hemophiliacs to allogeneic proteins via factor VIII concentrate for control of bleeding could lead to a state of chronic antigen stimulation. Immune function from eight hemophiliacs requiring large amounts of factor VIII concentrate was assessed. It was found that 5 of 8 had a positive blastogenic response to low concentrations of factor VIII in a 7-day thymidine uptake assay. Separation of lymphocyte subpopulations indicated that the reactivity was contained in the T cell-enriched fraction. There was no blast transformation noted secondary to the factor VIII product in 20 controls tested in a 7-day assay nor was there any mitogenic effect of the factor VIII in a 3-day assay. In fact, high concentrations of factor VIII impaired that T lymphocytes from hemophiliacs are antigenically primed to some constituent in the lyophilized factor VIII concentrate.

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Section: Resultssupporting

confidence: 92%

Section: Resultssupporting

confidence: 83%

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T Lymphocytes from Hemophiliacs Proliferate after Exposure to Factor VIII Product

Matheson¹,

Green²,

Poon³

et al. 1986

Vox Sanguinis

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“…Since chronic hepatitis C is present in 60-100% of adult hemophiliacs, it can be specu lated whether hepatitis C could be the com mon causative factor responsible for signs of immunosuppression in hemophilia in general [77], In support of this, a recent long-term study of immunologic parameters in HIVand HCV-antibody-negative children demon strated long-term stability in this cohort by means of lymphocyte subsets, lymphocyte proliferative activity, immunoglobulins, and recall antigen skin test response [78], and nor mal results of CD4 and CD8 cells and im mune globulin status detected in HIV-and HCV-antibody-negative hemophiliacs [79]. However, suspicion has been raised that allo genic protein impurities of factor concen trates [80] plus undefined material of lower molecular weight might be involved in sup pression of immune competent cells [81,82].…”

Section: Immunosuppressive Effects Of Plasma Derivativesmentioning

confidence: 99%

Safety of Plasma Derivatives

Ingerslev

1994

Pathophysiol Haemos Thromb

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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.

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T-Lymphozytenpopulation und -proliferation vor und während Substitution mit Faktor VIII-Konzentrat

Fey¹,

Walker²,

Pichler³

et al. 1986

2. Rundtischgespräch Therapiebedingte Infektionen Und Immundefekte Bei Hämophilen

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Inhibition of Human T Lymphocyte Proliferation in vitro by Commercial Factor VIII Concentrates

Cited by 3 publications

References 6 publications

T Lymphocytes from Hemophiliacs Proliferate after Exposure to Factor VIII Product

T Lymphocytes from Hemophiliacs Proliferate after Exposure to Factor VIII Product

Safety of Plasma Derivatives

T-Lymphozytenpopulation und -proliferation vor und während Substitution mit Faktor VIII-Konzentrat

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