[The "Seville" Consensus Document on Alternatives to Allogenic Blood Transfusion. Sociedades españolas de Anestesiología (SEDAR), Medicina Intensiva (SEMICYUC), Hematología y Hemoterapia (AEHH), Transfusión sanguínea (SETS) Trombosis y Hemostasia (SETH)]. / Documento «Sevilla¼ de Consenso sobre Alternativas a la Transfusión de Sangre Alogénica.

The Consensus Document on Alternatives to Allogenic Blood Transfusion (AABT) has been drawn up by a panel of experts from 5 scientific societies. The Spanish Societies of Anesthesiology (SEDAR), Critical Care Medicine and Coronary Units (SEMICYUC), Hematology and Hemotherapy (AEHH), Blood Transfusion (SETS) and Thrombosis and Hemostasis (SETH) have sponsored and participated in this Consensus Document. Alternatives to blood transfusion have been divided into pharmacological and non-pharmacological, with 4 modules and 12 topics. The main objective variable was the reduction of allogenic blood transfusions and/or the number of transfused patients. The extent to which this objective was achieved by each AABT was evaluated using the Delphi method, which classifies the grade of recommendation from A (supported by controlled studies) to E (non-controlled studies and expert opinion). The experts concluded that most of the indications for AABT were based on middle or low grades of recommendation, "C", "D", or "E", thus indicating the need for further controlled studies.

Documento «Sevilla» de Consenso sobre Alternativas a la Transfusión de Sangre Alogénica / The «Seville» Consensus Document on Alternatives to Allogenic Blood Transfusion

El Documento de Consenso sobre Alternativas a la Transfusión de Sangre Alogénica (ATSA) ha sido elaborado por un panel de expertos pertenecientes a 5 sociedades científicas. Han participado y patrocinado las sociedades españolas de Anestesiología (SEDAR), Medicina Intensiva (SEMICYUC), Hematología y Hemoterapia (AEHH), Transfusión sanguínea (SETS) y Trombosis y Hemostasia (SETH). Las alternativas a la transfusión se han clasificado en farmacológicas y no farmacológicas, con un total de 4 módulos y 12 tópicos. La disminución de las transfusiones de sangre alogénica y/o el número de pacientes transfundidos fue la principal variable objetivo. El grado de cumplimiento de este objetivo, para cada ATSA, se llevó a cabo siguiendo la metodología Delphi, que clasifica el grado de recomendación desde «A» (apoyado por estudios controlados) hasta «E» (estudios no controlados y opinión de expertos). Los expertos concluyeron que la mayor parte de las indicaciones de las ATSA se sustentan en grados de recomendación medios y bajos, «C», «D» o «E», precisándose nuevos estudios controlados (AU)

The Consensus Document on Alternatives to Allogenic Blood Transfusion (AABT) has been drawn up by a panel of experts from 5 scientific societies. The Spanish Societies of Anesthesiology (SEDAR), Critical Care Medicine and Coronary Units (SEMICYUC), Hematology and Hemotherapy (AEHH), Blood Transfusion (SETS) and Thrombosis and Hemostasis (SETH) have sponsored and participated in this Consensus Document. Alternatives to blood transfusion have been divided into pharmacological and non-pharmacological, with 4 modules and 12 topics. The main objective variable was the reduction of allogenic blood transfusions and/or the number of transfused patients. The extent to which this objective was achieved by each AABT was evaluated using the Delphi method, which classifies the grade of recommendation from A (supported by controlled studies) to E (non-controlled studies and expert opinion). The experts concluded that most of the indications for AABT were based on middle or low grades of recommendation, «C», «D», or «E», thus indicating the need for further controlled studies (AU)

The c.-1639G > A polymorphism of the VKORC1 gene is a major determinant of the response to acenocoumarol in anticoagulated patients.

Much of the variability in the sensitivity to warfarin in anticoagulated patients is associated with the c.-1639G > A polymorphism of the vitamin K-epoxide reductase (VKORC1) gene. However, its association with the acenocoumarol dose in patients under anticoagulant therapy has not been studied. The c.-1639G > A genotype of VKORC1 was determined in 113 patients on stable anticoagulation requiring low (n = 42), medium (n = 42) or high (n = 21) acenocoumarol doses. To evaluate the association between acenocoumarol requirements and the c.-1639G > A variant, multivariate logistic regression models were fitted, adjusting for age, gender, and the c.430C > T and c.1075A > C variants of cytochrome P450 2C9 (CYP2C9). A total of 90.5% of the patients in the low acenocoumarol dose group carried the A allele of VKORC1:c.-1639G > A. The A allele independently increased the odds of requiring a low acenocoumarol dose [odds ratio (OR) 9.4; 95% confidence interval (CI) 1.9-46.4; P = 0.006], especially when the homozygous form was present (OR 44.2; 95% CI 5.5-354.6; P < 0.001). The A allele was less frequent in the high dose group showing an inverse association with the requirement for high doses (OR 0.04; 95% CI 0.01-0.22; P < 0.001). The A allele of the c.-1639G > A polymorphism of VKORC1 is therefore associated with a low-dose requirement for acenocoumarol in patients receiving anticoagulant therapy.

Differential effects of 2C9*3 and 2C9*2 variants of cytochrome P-450 CYP2C9 on sensitivity to acenocoumarol.

The 2C9*3 and 2C9*2 polymorphisms of cytochrome P-450 CYP2C9 are associated with hypersensitivity to warfarin and bleeding. The effect of these polymorphisms on sensitivity to acenocoumarol is unknown. Three groups of patients, with low, medium, or high acenocoumarol-dose requirements, were studied. Age influenced the acenocoumarol sensitivity. Bearing the 2C9*3 allele was associated with the need for a lower acenocoumarol dose (odds ratio [OR], 6.02; 95% confidence interval [CI], 1.50-24.18); 80% of carriers of the 2C9*3 allele required a low dose. The 2C9*2 allele was associated with a lower acenocoumarol-dose requirement (OR, 2.70; 95% CI, 1.11-6.58) because of a reduced risk of the need for a high acenocoumarol dose (4.8% of the patients in the high-dose group carried the 2C9*2 allele versus 34.1% and 30.2%, respectively, in the medium-dose and low-dose groups). Therefore, carriers of 2C9*3 may need a low initial loading dose of acenocoumarol. Because acenocoumarol sensitivity with the 2C9*2 variant does not seem to be clinically relevant, the drug could be an alternative to warfarin in 2C9*2 carriers.