Vascular access thrombosis (VAT) is frequent in some hemodialysis patients. Antiphospholipid antibodies (APL) have been involved in thrombosis, and have been reported to be present in a high proportion of patients with chronic renal failure. We studied the relationship between APL and thrombosis in 97 hemodialysis patients (HD). Lupus anticoagulant (LA) was assessed by activated partial thromboplastin time (APTT) and by tissue thromboplastin inhibition assay (TTI). IgG-anticardiolipin (ACA) was measured by a solid phase ELISA. The prevalence of APL was 31%; LA was found in 16.5% and was detected in all cases by TTI. Only one patient was positive for APTT. ACA was found in 15.5%. Only one patient was positive for LA and ACA. We found no relation between APL and age, length of time on dialysis, sex, type of dialysis membrane, drugs, and chronic B and C hepatitis. A high prevalence of APL was found in patients with undetermined nephropathy. When histories of thrombosis were examined, VAT was found to be significantly more frequent in patients with LA than in patients without LA (62% vs. 26%; P = 0.01). This relation was not present with ACA. Since VAT is one of the most frequent causes of morbidity for HD, diagnostic evaluation of VAT in HD should now include assay for LA.

To screen for point mutations causing protein S deficiency, we used a sequence of techniques specifically for the study of the protein S active gene, PS alpha. This strategy comprises amplification of exons and intron/exon junctions by means of the polymerase chain reaction (PCR) and electrophoresis of the amplified fragments in polyacrylamide gel containing a gradient of denaturing agents (denaturing gradient gel electrophoresis). Only fragments with altered melting behavior are sequenced after asymmetric PCR. Beside the frequent polymorphism already described on Pro 626, we detected 18 different sequence variations by studying exons II, IV, V, VIII, X, and XV in 19 of 100 consecutive patients with protein S deficiency. Fifteen were candidate causal mutations, 4 of which were associated with a qualitative deficiency (type IIa or IIb). The remaining three sequence variations were probably polymorphisms.

Elevated plasma IL-6 levels have been implicated in the pathogenesis of coronary heart disease. We have investigated the association of two polymorphisms in the promoter of IL-6 (-572G>C and -174G>C) with levels of inflammatory markers and risk of myocardial infarction (MI) in a European study of MI survivors and age-matched controls from two high-risk centres in the North of Europe, and two low risk centres in the South. IL-6 and CRP levels were similar in controls in both regions, but were higher in cases. For the -174G>C polymorphism the rare -174C allele showed a regional difference in allele frequency, being more common in the North European group (0.43 vs 0.28; p < 0.0005), where -174C allele carriers showed an apparent reduced risk of MI compared to -174GG homozygotes (OR 0.53, 95%CI 0.32, 0.86). No such effect was observed in the South or with the -572G>C in either group. Neither genotype was associated with a significant effect on plasma IL-6 levels in either cases or controls. Furthermore, no regional difference was observed in the frequency of the -572G>C SNP, suggesting that these polymorphisms are unlikely to be contributing to the observed increased risk of cardiovascular disease in Northern Europe.

Abstract-Identification of combined genetic factors in factor V Leiden carriers is important for a more accurate risk assessment for venous thrombosis (VT). Among these individuals, we evaluated the role of polymorphisms of the plasminogen activator inhibitor-1 (PAI-1) gene in the thrombophilic phenotype. A total of 382 factor V Leiden carriers were included in the study. This population was divided into 3 groups. Group 1 (nϭ168) included individuals with a personal history of VT; group 2 (nϭ140) included individuals without personal VT but with a familial history of VT; and group 3 (nϭ74) included individuals without VT and with a fortuitous discovery of the factor V Leiden mutation. We compared the genotype distribution of 2 polymorphisms, A Ϫ844G and Ϫ675 4G/5G, located in the promoter region of the PAI-1 gene among these 3 groups of individuals. The A Ϫ844G allele frequency differed significantly among the 3 groups (Pϭ0.048), the A allele being more frequent in patients who suffered from VT (61%) than in subjects without VT (52%, Pϭ0.015), whereas no difference was observed between the 2 groups of asymptomatic individuals. The prevalence of genotype AA carriers was higher in patients with VT (38%) than in asymptomatic individuals (21%, Pϭ0.015), leading to an odds ratio of 1.74 (95% confidence interval, 1.3 to 3.8). Carrying the AA genotype conferred a risk of deep VT of 2.08 (95% confidence interval, 1.28 to 3.40), whereas it did not seem to significantly influence the risk of pulmonary embolism. Concerning the Ϫ675 4G/5G polymorphism, no significant difference was observed among the 3 groups, the 4G allele frequency being 0.54 (in group 1), 0.49 (in group 2), and 0.45 (in group 3). These data suggest a role for the ϪA844G PAI-1 gene polymorphism in the thrombophilic phenotype of factor V Leiden carriers. Key Words: PAI-1 Ⅲ genetic polymorphisms Ⅲ venous thrombosis Ⅲ factor V Leiden