Blood donors on medication. Are deferral periods necessary?

OBJECTIVES: Drugs and their metabolites in transfused blood components may cause effects in the recipient. If the treated disorder is not to be regarded as an exclusion criterion from blood donation, donors on medication should be deferred for a period consistent with the drug's pharmacokinetics. GENERAL PRINCIPLES AND METHODS: Peak plasma drug concentrations of 3% or less of the therapeutic concentration were regarded to be safe for the recipient of a blood product. For teratogenic drugs a much lower safety level of less than 0.000001% has been proposed. For the calculation of deferral periods, both the type of blood component to be prepared and the drug's pharmacokinetics for a given formulation were considered. SUGGESTED WAITING PERIODS: For drugs with known teratogenic risks, we suggest a deferral period of 28 plasma-elimination half-lives. For non-teratogenic drugs, a simple, conservative approach could be based on waiting for five plasma-elimination half-lives, thus reaching the required 3% safety level already in any donor. If, however, the type of blood component to be prepared is also considered, a more differentiated approach appears to be appropriate: for blood components containing 50 ml or less plasma from a single donor, donor medication may be disregarded because of the high dilution in the recipient's plasma volume, whereas for blood components with higher plasma contents (250 ml on average) from a single donor on medication the 3% safety level will be achieved by observing the deferral period of five plasma-elimination half-lives mentioned. A guideline for 191 drugs and drug classes has been elaborated accordingly.

Pathophysiological effects of endothelial cytotoxic activity derived from sera of patients with progressive systemic sclerosis.

Endothelial cytotoxic activity prepared from sera of patients with progressive systemic sclerosis (PSS) causes changes in endothelial cell physiology in vitro and in vivo. In the presence of endothelial cytotoxic activity human endothelial cell migration and fibronectin production in vitro were strongly reduced. Repeated intravenous injection of 1 ml partially purified endothelial cytotoxic activity IV once a week into rabbits caused a significant increase of serum FVIIIR: Ag, changes in endothelial cells morphology, and generalized dilatation of capillaries. Taken together, these results support the hypothesis that endothelial cytotoxic activity is a slow acting material which may initiate the obliterative vasculopathy in PSS by chronic damage of endothelial cells.

Identification of an LtB4-protein complex as evidence of endothelial cell cytotoxic activity (ECA) in progressive systemic sclerosis (PSS).

A low molecular weight LtB4-carrier complex has been identified as endothelial cytotoxic activity (ECA) in progressive systemic sclerosis (PSS) patients' sera. ECA is thought to play a key role in the initiation of obliterative vasculopathy, a basic tissue lesion of this disease.

[Analysis of T-cell subpopulations. Pathophysiological concept and significance for clinical medicine]. / Analyse von T-Zell-Subpopulationen. Pathophysiologisches Konzept und Bedeutung für die Klinik.

Two T-lymphocyte subsets develop in the thymus which differ in the expression of glycoproteins on their cell surface. About 60% of the circulating T cells express the glycoprotein T4, while about 30% have the glycoprotein T8. T4 and T8 cells can be determined in the peripheral blood or various organs with monoclonal antibodies. T4 and T8 cells differ in their antigen recognition, have different functions, and can cause various pathohistological changes. T4 cells recognize the antigen in association with the HLA-D/DR/DP determinants. Upon antigenic stimulation they liberate various factors and initiate and amplify an immune response (T4 = helper/inducer T-cells). They can also be cytotoxic and are mediating effector functions via macrophage activation. T8 cells recognize the antigen in association with HLA-A/B/C determinants. They exert their cytotoxic or suppressive effector functions mainly in viral infections. The T4 or T8 cell-mediated pathohistological changes are discussed in the light of the well studied T-cell infiltrations in lepra lepromatosa or lepra tuberculosa. The T4/T8 cell dyscrasia in the peripheral blood, described in a variety of infectious, autoimmune or immunodeficiency diseases, may be due to enhanced proliferation, selective sequestration, reduced production or the elimination of a subset. T-cell subset analysis in joints, bronchial lavages and tissues has clarified the pathomechanism in a variety of autoimmune diseases, although the etiology remains obscure. For example, in rheumatoid arthritis, multiple sclerosis, and sarcoidosis, a T4 cell-mediated reaction with macrophage activation can be found. T4/T8 cell analysis may also be of value in dissecting heterogenous diseases, e.g. systemic lupus erythematosus. Of value is also the additional demonstration of membrane components reflecting T-cell activation (IL-2 receptor or DR-antigen expression) which serves to identify the activated T-cell subset in peripheral blood. Finally, T4/T8 cell analysis can be helpful in deciding treatment, as the T-cell subsets have a different sensitivity to immunosuppressive drugs.

Rat malarial glomerulonephritis. An experimental model of post-infectious glomerular injury.

This paper describes the immunopathologic findings in acute malaria-associated glomerulonephritis in the rat. Young Sprague-Dawley rats were infected with Plasmodium berghei berghei. The subsequent parasitemia and elevation of circulating Clq-reactive immune complexes were transient while the appearance of anti-plasmodial antibody in the serum was persistent. Sequential examination of renal tissue and urine revealed the following glomerular alterations: (a) granular, predominantly mesangial deposits of IgG, IgM, and C 3, (b) electron dense deposits in the mesangial matrix, (c) glomerular deposition of plasmodial antigen(s) and of anti-plasmodial antibody as demonstrated by acid elution studies, (d) hypercellularity of the glomerular tufts and (e) increased urinary excretion of high molecular weight proteins. All renal abnormalities were transitory, disappearing within one to three months. The results indicate that this form of acute malarial glomerulonephritis in rats is mediated by immune complexes involving plasmodial antigen. The disease resembles the transient glomerular injury complicating cases of Plasmodium falciparum infection in humans. As an easily reproducible model, rat malarial glomerulonephritis appears most suitable for further immunopathologic and functional studies of post-infectious glomerular disease.