tacrolimus and Blood-Coagulation-Disorders

The heterogeneous Brazilian population, with European, African and Amerindian ancestral roots is a model case for exploring the impact of population admixture on the frequency distribution of polymorphisms in pharmacogenes, and the design and interpretation of pharmacogenomics trials. Examples drawn from studies carried out by researchers of the Brazilian pharmacogenomics network, support the following conclusions: the distribution of polymorphisms varies across geographical regions and self-reported 'race/color' categories, and is best modeled as continuous functions of individual proportions of European and African ancestry; the differential frequency of polymorphisms impacts the calculations of sample sizes required for adequate statistical power in clinical trials performed in different segments of the Brazilian population; and extrapolation of pharmacogenomics data from well-defined ethnic groups to Brazilians is plagued with uncertainty. Data for warfarin and tacrolimus are reviewed to highlight the advantages and challenges of performing pharmacogenomic trials in Brazilians.

Topics: Blood Coagulation Disorders; Brazil; Ethnicity; Genetics, Population; Haplotypes; Humans; Immunosuppression Therapy; Pharmacogenetics; Polymorphism, Single Nucleotide; Tacrolimus; Warfarin

We performed 13 pediatric liver transplants from ABO-incompatible living related maternal or paternal donors using a combination of preoperative removal of isohemagglutinin and postoperative immunosuppressive therapy with FK506 and prophylactic OKT3. Tissue near-infrared spectroscopy was applied to evaluate hemodynamics using the hemoglobin of red cells in the sinusoids as an index. The data obtained indicated that the preoperative removal of isohemagglutinin prevented hyperacute humoral rejection with hemorrhagic infiltration in the sinusoids in 10 successful cases. The incidence of acute rejection was not significantly different among ABO-identical, -compatible, and -incompatible groups. The estimated 1-year survival rate of the ABO-incompatible group was 77%.

Topics: ABO Blood-Group System; Blood Circulation; Blood Coagulation Disorders; Child, Preschool; Female; Graft Rejection; Graft Survival; Hemodynamics; Hemoglobins; Humans; Incidence; Liver Transplantation; Male; Muromonab-CD3; Spectrophotometry, Infrared; Tacrolimus; Tissue Donors