Eduardo Muñiz-Díaz

Functional Effects of the ABO Locus Polymorphism on Plasma Levels of von Willebrand Factor, Factor VIII, and Activated Partial Thromboplastin Time

Lower levels of factor VIII and von Willebrand factor (vWF) have been reported in individuals with blood type O compared with individuals with other ABO blood types. However, this relationship has been demonstrated only by association studies and not by linkage studies. Also, it is not clear whether the ABO locus exerts a functional effect directly on these plasma factors or whether the ABO locus is in linkage disequilibrium with another locus that controls these factors. To distinguish between these 2 possibilities, we applied new statistical methods combining linkage and association tests in a pedigree-based sample. In contrast to most previous studies that used the ABO phenotypes, our study used the ABO genotypes, permitting us to distinguish AO from AA and BO from BB. Our results clearly showed significant linkage between the ABO locus and vWF antigen (P=0.00075). In addition, factor VIII coagulant activity and activated partial thromboplastin time showed suggestive linkage with the ABO locus (P=0.10 and P=0.13). All 3 plasma phenotypes showed significant differences between OO and non-OO genotypes. In addition, vWF antigen exhibited significant differences between O heterozygotes and non-OO homozygotes. This study is unique because it used a combined linkage and association test, which indicated that the ABO locus itself has a functional effect on these plasma phenotypes.

Associations between Fc gamma receptor IIA polymorphisms and the risk and prognosis of meningococcal disease

BACKGROUND In vitro studies have shown that the neutrophil Fc gamma receptor IIA (FcgammaRIIA) polymorphism influences the phagocytic capacity of neutrophils and the removal of encapsulated bacteria from the bloodstream. In particular, the R/R131 allotype is associated with less phagocytic activity. SUBJECTS AND METHODS We performed a case-control study to determine the influence of the FcgammaRIIA polymorphism (R/R131, R/H131, H/H131) on the risk and outcome of meningococcal disease. The polymorphisms were measured in 130 patients with microbiologically proven meningococcal disease diagnosed from 1987 to 1998 (cases) and 260 asymptomatic sex-matched blood donors (controls). Clinical manifestations and complications of meningococcal disease were recorded, and a prognostic score (based on age, hemorrhagic diathesis, neurologic signs, and the absence of preadmission antibiotic) therapy was calculated. RESULTS The distributions of FcgammaRIIA allotypes were similar in cases and controls. However, among patients with meningococcal infection, fulminant meningococcal disease (odds ratio [OR] = 3.9; 95% confidence interval [CI]: 1.0 to 16; P = 0.04) and meningococcemia without meningitis (OR = 3.0; 95% CI: 1.4 to 7.8; P = 0.004) were more common in those with the FcgammaRIIA-R/R131 allotype. Complications were also significantly more frequent in these patients. Of the 42 patients with the R/R131 allotype, 31 (74%) had an adverse prognostic score, compared with 7% (4 of 59) of those with the R/H131 allotype and 3% (1 of 29) of those with the H/H131 allotype (P <0.0001). CONCLUSION The FcgammaRIIA-R/R131 allotype is associated with more severe forms of meningococcal disease.

Aprotinin versus desmopressin for patients undergoing operations with cardiopulmonary bypass: A double-blind placebo-controlled study

BACKGROUND Aprotinin reduces blood loss in operations done with cardiopulmonary bypass, whereas the use of desmopressin remains controversial. We compared aprotinin, desmopressin, and placebo in a double-blind, randomized trial to evaluate bleeding and transfusion requirements. METHODS AND RESULTS One hundred forty-nine patients (48 received aprotinin, 50 desmopressin, 51 placebo) were included. Blood loss and transfusion requirements were recorded and levels of Factor VIII coagulant activity, von Willebrands factor, thrombin-antithrombin complexes, and D-dimer were measured. Overall blood loss was 195 +/- 146 ml/m2 in the aprotinin group, 400 +/- 192 ml/m2 in the desmopressin group, and 489 +/- 361 ml/m2 in the placebo group (95% confidence intervals: difference between desmopressin and aprotinin 98 to 312 ml/m2, p < 0.001; difference between placebo and aprotinin 190 to 398 ml/m2, p < 0.001). Twenty-six percent of patients treated with aprotinin, 66% of those treated with desmopressin, and 56% of those treated with placebo were given transfusion (95% confidence intervals: difference between aprotinin versus placebo plus desmopressin 51% to 71%, p < 0.001). Fibrinolytic activation throughout cardiopulmonary bypass was markedly higher with placebo or desmopressin administration. D-dimer level correlated with overall blood loss in patients receiving desmopressin or placebo, but not in those receiving aprotinin. CONCLUSION Aprotinin administration reduces blood loss and transfusion requirements in cardiopulmonary bypass. This benefit may be explained by a lower activation of fibrinolysis.

Relevance of genetically determined host factors to the prognosis of meningococcal disease

To assess the relevance of genetically determined host factors for the prognosis of meningococcal disease, Fc gamma receptor IIA (FcγRIIA), the tumor necrosis factor alpha (TNF-α) gene promoter region, and plasminogen-activator-inhibitor-1 (PAI-1) gene polymorphisms were studied in 145 patients with meningococcal disease and in 290 healthy controls matched by sex. Distribution of FcγRIIA, TNF-α, and PAI-1 alleles was not significantly different between patients and controls. Patients with the FcγRIIA-R/R 131 allotype scored ≥1 point in the Barcelona prognostic system more frequently than patients with other allotypes (odds ratio, 18.6; 95% confidence interval, 7.1–49.0, P<0.0001), and they had a higher risk of sequelae (odds ratio, 3.5; 95% confidence interval, 1.1–11.7; P=0.03). Fc gamma receptor IIA polymorphism was associated with markers of disease severity, but TNF-α and PAI-1 polymorphisms were not.

Refractariedad a las transfusiones de plaquetas

La refractariedad es una de las complicaciones inducidas por las transfusiones de plaquetas que, en ocasiones, puede resultar muy grave. En general, se acepta que el paciente es refractario cuando tras dos transfusiones consecutivas no se produce el incremento esperado en la cifra de plaquetas 1,2 . No es posible estimar el indice real de refractariedad entre los pacientes repetidamente transfundidos porque los criterios empleados para catalogar al paciente como refractario no son uniformes. Sin embargo, existe un acuerdo unanime al senalar que en los ultimos anos se viene observando un descenso del indice de refractariedad. En 1991 se estimaba que aproximadamente un 50% de los pacientes politransfundidos se hacian refractarios 3 , y 6 anos despues este indice se redujo hasta un 16% 4 . Las causas

New types of granulocyte inclusions in hereditary macrothrombocytopenias

ment d’Hematologia, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Núria Pujol-Moix, Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain; Mercè Durfort, Departament de Biologia Cellular, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain. Correspondence to: Dr. Núria Pujol-Moix, Hospital de la Santa Creu i Sant Pau, Departament d’Hematologia, Sant Antoni M. Claret 167, 08025-Barcelona, Spain. Tel.: +34-93-2919246; Fax: +34-93-2919192. E-mail: npujol@hsp.santpau.e s Letter to the Editor