Antibody levels to the class I and II epitopes of the M protein and myosin are related to group A streptococcal exposure in endemic populations.

Rheumatic fever (RF)/rheumatic heart disease (RHD) and post-streptococcal glomerulonephritis are thought to be autoimmune diseases, and follow group A streptococcal (GAS) infection. Different GAS M types have been associated with rheumatogenicity or nephritogenicity and categorized into either of two distinct classes (I or II) based on amino acid sequences present within the repeat region ('C' repeats) of the M protein. Sera from ARF patients have previously been shown to contain elevated levels of antibodies to the class I-specific epitope and myosin with the class I-specific antibodies also being cross-reactive to myosin, suggesting a disease association. This study shows that immunoreactivity of the class I-specific peptide and myosin does not differ between controls and acute RF (ARF)/RHD in populations that are highly endemic for GAS, raising the possibility that the association is related to GAS exposure, not the presence of ARF/RHD. Peptide inhibition studies suggest that the class I epitope may be conformational and residue 10 of the peptide is critical for antibody binding. We demonstrate that correlation of antibody levels between the class I and II epitope is due to class II-specific antibodies recognizing a common epitope with class I which is contained within the sequence RDL-ASRE. Our results suggest that antibody prevalence to class I and II epitopes and myosin is associated with GAS exposure, and that antibodies to these epitopes are not an indicator of disease nor a pathogenic factor in endemic populations.

Lack of association between factor V Leiden and thromboembolism in patients with prosthetic heart valves.

Thromboembolism represents the most serious complication in patients with prosthetic heart valves, and causes significant mortality and morbidity. Many risk factors for the condition have been identified. However, many patients who have a therapeutic level of anticoagulation and no obvious risk factors develop thromboembolism. Factor V Leiden, found in 3-7% of the normal population, is the most common inherited factor associated with thrombosis. Whether or not this factor is associated with thromboembolism in this setting has not been explored. This study compares the prevalence of factor V Leiden in patients with prosthetic heart valves, with and without thromboembolic complications. A total of 148 patients were studied. Thirty had documented thromboembolic complications and none exhibited the factor V mutation. Of the 118 patients without thromboembolic complications, seven (5.9%) were heterozygous for factor V Leiden (P = 0.345, by Fisher's two-tailed exact test; odds ratio 0, 95% confidence interval 0.0-4.34). We conclude that until future data shows otherwise, routine testing for factor V Leiden in patients with prosthetic heart valves is not warranted, except as part of ongoing research.

Association of factor V Leiden with Behçet's disease.

OBJECTIVE: Studies show an association between factor V Leiden and venous thrombosis. Since venous thrombosis is common in Behçet's disease (BD), we looked for an association between thrombosis in BD and the presence of factor V Leiden. METHODS: Twenty-three patients with BD according to International Study Group criteria and 22 patients with rheumatoid arthritis by American College of Rheumatology criteria as controls participated in the study. Patients with BD and controls were tested for the presence of factor V Leiden by polymerase chain reaction (PCR) amplification of genomic DNA and by restriction enzymatic analysis of PCR products. RESULTS: Three of 23 patients with BD were positive for factor V Leiden (13%). Among BD patients without thrombosis 0/15 were positive; among those with thrombosis 3 of 8 were positive (37.5%) for factor V. Only one patient with RA was positive for factor V Leiden. CONCLUSION. The presence of factor V Leiden in patients with BD may markedly increase the risk of thrombosis.

Dental procedures in patients receiving oral anticoagulation therapy.

Over a 10-year period a uniform management plan for patients receiving long term oral anticoagulation therapy for prosthetic heart valves and needing dental procedures was instituted. Those undergoing dental extraction or gum hygiene in the presence of gross gum pathology (Group A) had their oral anticoagulation discontinued two days prior to the procedure which was carried out only if the INR was 1.5 or less on the day of the procedure. Patients who needed dental fillings or gum hygiene in the absence of gross gum pathology (Group B) continued their anticoagulation therapy and had these procedures completed provided the INR was 3.0 or less. The main outcome measured were valve thrombosis, thromboembolism and excessive bleeding requiring hospitalization and/or blood transfusion. In Group A, 240 procedures were carried out; 212 dental extractions and 28 dental hygiene in the presence of gross gum pathology. They had a brief period of under-anticoagulation (3-7 days) to an INR of 1.5 or less. In Group B, 156 procedures were performed. No patient developed valve thrombosis or thromboembolism. Two patients, both in Group A needed hospitalization for observation but no blood transfusion. This management plan was easy to implement. Patients needed one extra visit to the anticoagulation clinic within one week of the procedure. It was both safe and effective.