Comparative hemolytic activity of undiluted organic water-miscible solvents for intravenous and intra-arterial injection.

In humans, nonaqueous solvents are administered intravascularly in two kinds of situations. They have been used in subcutaneous or intramuscular pharmaceutical formulations to dissolve water-insoluble drugs. The need for these vehicles had increased in recent years, since the drug development process has yielded many poorly water-soluble drugs. The use of water-miscible nonaqueous solvents in therefore one of the approaches for administering these products as reference solutions useful in formulation bioequivalence studies. The intravascular use of organic solvents has also gained importance owing to a new approach for the treatment of cerebral malformations using precipitating polymers dissolved in water-miscible organic solvents. At present, the solvent most commonly used for the liquid embolics to solubilize the polymers is dimethyl sulfoxide, which exhibits some local and hemodynamic toxicities. In order to find new, less toxic vehicles for pharmaceutical formulations for the intravenous and intra-arterial routes and for embolic materials, 13 water-miscible organic solvents currently used (diluted with water) for pharmaceutical applications, were evaluated in this study. Their hemolytic activity and the morphological changes induced when mixed with blood (1:99, 5:95, 10:90 solvent:blood) were estimated in vitro. From these data, the selected organic solvents could be subdivided into four groups depending on their hemolytic activity: very highly hemolytic solvents (ethyl lactate, dimethyl sulfoxide), highly hemolytic solvents (polyethylene glycol 200, acetone), moderately hemolytic solvents (tetrahydrofurfuryl alcohol, N-methyl-2-pyrrolidone, glycerol formal, ethanol, Solketal, glycofurol) and solvents with low hemolytic activity (propylene glycol, dimethyl isosorbide, diglyme).

Successful treatment of neonatal rhesus hemolytic anemia with high doses of recombinant human erythropoietin.

The authors report the use of high-dose recombinant erythropoietin (r-HuEPO) in a full-term newborn baby with severe postnatal rhesus hemolytic anemia (RHA). Hemoglobin (Hb) value and reticulocyte count at day 13 of life were 59 g/L and 234 x 10(9)/L, respectively. Three days after the r-HuEPO (870 U/kg/d) administration, reticulocyte count had increased more than 4-fold and Hb rose to 73 g/L. r-HuEPO was gradually decreased after 18 days of treatment. No major side effect was observed. In selected cases of severe anemia due to hemolytic disorders, transfusions may be avoided by the use of high doses of r-HuEPO.

Massive delayed hemolysis following peripheral blood stem cell transplantation with minor ABO incompatibility.

After hematopoietic stem cell transplantation, delayed immune hemolysis may occur when donor-derived B lymphocytes carried with the graft produce immune antibodies against the recipient's incompatible red cells. We report the occurrence of this syndrome in the context of minor blood group incompatibility between donor and recipient after peripheral blood stem cell (PBSC) transplantation. On day 12 post-transplant there was abrupt onset of hemolysis necessitating supportive treatment with hydration and transfusions. Because, as compared to bone marrow, PBSC grafts are enriched with lymphocytes, more frequent and intense delayed immune hemolysis may be anticipated when using PBSC. This complication is described most often when cyclosporine alone is used for immunosuppression following the graft. The addition of methotrexate, which with CyA forms the classic regimen for the prevention of graft-vs-host disease, may diminish the frequence and severity of this adverse reaction.

[Prevention of viral recurrence following liver transplantation for post-hepatitis B and B-delta cirrhosis]. / Prévention de la récidive virale après transplantation hépatique pour cirrhose post-hépatitique B et B-delta.

The incidence of recurrence of hepatitis B virus (HBV) following orthotopic liver transplantation (OLT) is as high as 80% when no attempt at prevention has been considered. HBV reinfection is associated with the reappearance of hepatitis B surface antigen (HBsAg) and HBV DNA in serum and, in most cases, with rapid severe graft damage. Immunoprophylaxis using polyclonal anti-HBs immunoglobulins reduces the risk of recurrence but this long-term therapy remains highly expensive. In this report, we use fresh frozen plasma (FFP) with high titers of anti-HBs immunoglobulins in an attempt to reduce HBV recurrence. From July 1987 to September 1993, 11 patients underwent OLT for HBV-related liver disease (18% of our OLT patients). FFP were administered to 6 patients continually for 7 to 46 months. Only one patient, under long-term immunosuppressive treatment before OLT, was reinfected 7 months after OLT. Rapid development of graft failure was observed with histologic manifestations of a fibrosing cholestatic hepatitis, leading to patient death after 12.5 months with concomitant bacterial infection. In this protocol, the rate of reappearance of HBsAg was 17%, a figure which can be favorably compared with other reports. All patients were subsequently tested for HCV and HIV and remained negative. In conclusion, FFP with high titers of anti-HBs immunoglobulins is at least as effective as polyclonal anti-HBs immunoglobulins in reducing the rate of HBV recurrence following OLT. The estimated cost of this new immunoprophylaxis method is less than 10% of the classical prophylaxis based on purified human polyclonal anti-HBs immunoglobulins.