A critical evaluation of the prothrombin time for monitoring oral anticoagulant therapy

The Quick prothrombin time is the most common clotting test performed, principally for monitoring oral anticoagulant therapy. The International Normalized Ratio (INR) for comparing patient results from prothrombin time measurements and the International Standardized Index (ISI) for achieving greater consistency of results using different thromboplastins have made it possible to compare the results of vitamin K antagonist drug therapy that was impossible before the introduction of the INR and ISI. However, INR values obtained from the same patient plasma sample using different thromboplastins are significantly different. This is so even when the thromboplastins have nearly the same ISI values. We suggest that investigation of patient-specific differences can provide a means by which the INR discrepancies can be identified and understood and thus lead to better methods for monitoring oral anticoagulant therapy.     

Prothrombin time in the monitoring of oral anticoagulant: a comparison of results using different thromboplastins

The objective of this report is to compare the prothrombin time performed with thromboplastin of different tissues and species in patients under oral anticoagulant therapy as well as the way of expressing the results. The results showed that the ISI of the thromboplastin of human and rabbit brain are very close to the IRP BCT/253 (1.2 vs 1.1) and RBT/79 (1.3 vs 1.4), respectively. In contrast, the rabbit lung thromboplastin showed the greatest differences in the ISI values (1.6 vs 1.4) and in the CV (6.1%). The authors found significant statistical differences with the results of the prothrombin time as expressed in activity percentage (p less than 0.001) in three plasma pools of patients under different oral anticoagulant level for all thromboplastins studied. However, if the results are expressed in terms of INR, the values obtained are almost the same. The results here reported would demonstrate that the prothrombin time as INR allows the use of only one scheme for oral anticoagulant control when the thromboplastin reagent is calibrated according to the recommendations of the WHO.     

Frequency and clinical implications of lupus anticoagulant in patients with terminal chronic renal failure in hemodialysis

The objective of the present study was to determine the frequency of lupus anticoagulant (LA), in patients with terminal chronic renal failure (TCRF), and its association with thrombotic events. Sixty three patients were separated into two groups: Group A, consisted of 32 patients under treatment with hemodialysis, and Group B was formed of 31 patients who were treated in a conservative manner. Presence of LA was found in 4 patients from Group A and none from Group B. Seven thrombotic events were registered, all in patients from Group A, and three of the episodes happened in 2 patients with LA, showing a statistically significant difference with LA negative patients from the same Group A (p < 0.001). Three of the LA positive patients suffered from type 2 diabetes and all of them had been under dialysis for less obtained by than 6 months. Vascular access was catheterization which means that 57.1% of patients with this type of procedure were positive for LA. The present results show a strong relationship between the presence of LA and thrombotic episodes in patients with TCRF, under hemodialysis with the use of catheter, instead of a permanent vascular access. Due to the fact that prolonged use of catheters for hemodialysis has been related to positive LA, it is advisable to screen patients under dialysis for the presence of this antibody, and to promote the prompt availability of a permanent vascular access, in order to prevent complications, such as thrombosis.     

Perceived advantages and disadvantages of oral anticoagulants,and the trade-offs patients make in choosing anticoagulant therapy and adhering to their drug regimen

Objective

The objective of this study was to explore the perceived advantages and disadvantages of oral anticoagulant therapies (OAT), and the trade-offs patients make in choosing therapy and adhering to their drug regimen.

Gastroduodenoscopy for screening of patients scheduled for oral anticoagulant therapy: incidence and age dependence for potentially bleeding pathologies

This retrospective study was designed to shed light on the incidence and age-dependence of potentially bleeding pathologies in the upper gastrointestinal tract of asymptomatic patients scheduled for oral anticoagulant therapy. Gastroduodenoscopy was routinely performed during screening studies. The incidence of abnormalities was compared with gastroscopy findings of patients with epigastric symptoms. Only pathologies likely to bleed were considered. These included gastric ulcers, duodenal ulcers, esophageal varices, esophagitis, erosions, malformations and hemorrhages. RESULTS: 18.23% of the patients (n = 746) undergoing gastroscopy prior to scheduled oral anticoagulant therapy were found to present with abnormalities versus 18.44% of those with epigastric symptoms (n = 1,627). In the group scheduled for oral anticoagulant therapy, the rate of pathologies did not significantly increase with increasing age. CONCLUSIONS: The unexpectedly high incidence of potentially bleeding pathologies in asymptomatic patients scheduled for anti-coagulant therapy should prompt screening gastroduodenoscopies irrespective of the patients' age prior to instituting treatment.     

Prothrombin times and activated partial thromboplastin times in toxicology: a comparison of different blood withdrawal sites for wistar rats

The prothrombin time (PT) and the activated partial thromboplastin time (APTT) for untreated male Wistar rats were determined on the Sysmex CA-5000 Instrument for blood taken from the orbital sinus, tail vein, vena cava and aorta. Boxplot and statistical analysis was performed. Only orbital sinus puncture yields unpredictable and unacceptable variation/prolongation of clotting times.     

Self-management of oral anticoagulants with a whole blood prothrombin-time monitor in elderly patients with atrial fibrillation

The efficacy of oral anticoagulants (OAC) in reducing the incidence of stroke in elderly patients with atrial fibrillation (AF) has been well documented. The intensity of OAC therapy and deviations in the prothrombin time (PT) are the strongest risk factor for bleeding complications in elderly patients. The aim of this study was to evaluate a more rigorous regulation of OAC by the use of a portable whole blood PT-monitor (CoaguChek) in elderly patients with AF (age 65-80 years). The study group consisted of 20 patients, of whom 17 were evaluable, which were trained to use to CoaguChek monitor and adjust their anticoagulant dose for 12 months. The control group, 20 patients matched for age, gender and the duration of OAC treatment, were tested in an anticoagulant clinic and their OAC dose was adjusted by a physician. To validate the PT-monitor results, the patients performed a total of 129 simultaneous venous blood PT tests at various time points. The correlation coefficient R(2) was 0.707 indicating the accuracy of the CoaguChek results. The self-managed patients perform more frequent measurements 46 +/- 8.9 vs. 15.7 +/- 3.1 PT tests per patient. They demonstrated a within the therapeutic range INR in 80.5% of the tests (95% confidence interval, 76.5-84.1%) as compared to 72.4% (95% confidence interval, 68.5-76.5%) in the control group (p = 0.057). The median value for all CoaguChek International Normalized Ratio (INR) recordings was within therapeutic range in the self-management group as well as in the control group. There were fewer INR results below or above the therapeutic range in the study group. None of the patients had hemorrhagic or thrombotic events during the study. Overall, the study group expressed high satisfaction from using the home monitor. We conclude that home PT monitoring and self-management of OAC are feasible in a motivated population of elderly patients with atrial fibrillation and are probably cost effective.     

Low frequency of anti-SLA/LP autoantibody in Japanese adult patients with autoimmune liver diseases: analysis with recombinant antigen assay

Anti-soluble liver antigen/liver pancreas (SLA/LP) autoantibody has been proposed to be one of the autoantibodies characterizing autoimmune hepatitis (AIH). Recently, one of the autoantigens to anti-SLA/LP was identified as a UGA suppressor tRNA-associated protein. Although the function of this protein remains unknown, the recombinant protein has been prokaryotically expressed. Using this protein as an antigen, a recombinant immunoassay for anti-SLA/LP autoantibody has been established and the frequency and significance of this autoantibody have been discussed in European countries. So, in the present study, we investigated anti-SLA/LP autoantibodies in Japanese patients with autoimmune liver diseases using the recombinant antigen ELISA and Western blot assay. Seventy-five patients with AIH type 1, 5 with AIH type 2, 46 with primary biliary cirrhosis, 10 with primary sclerosing cholangitis, 47 with chronic hepatitis C, 48 with systemic lupus erythematosus, 3 with cryptogenic hepatitis, and 40 normal controls were the subjects of the present study. Anti-SLA/LP autoantibodies were detected in only 5 of 75 (6.7%) patients with AIH type 1, but in none of the other 159 patients or 40 normal controls. The clinicopathologic features of anti-SLA/LP-positive AIH type 1, including carriers of HLA DR locus variations, were not significantly different from anti-SLA/LP-negative patients except for the mortality rate. Anti-SLA/LP autoantibody was detected at a low frequency in Japanese patients with AIH type 1 and did not significantly influence clinical features. However, since it has high disease-specificity to AIH type 1, further analysis of SLA/LP may contribute to help clarify the pathogenesis of AIH type 1.     

Special report: a simple system for the derivation of International Normalized Ratios for the reporting of prothrombin time results with North American thromboplastin reagents

The World Health Organization international scale of reporting prothrombin time results is based on the calibration of thromboplastins against an international reference preparation to derive an International Sensitivity Index (ISI). Once the ISI has been assigned to an individual thromboplastin reagent, the derivation of International Normalised Ratios (INRs) for reporting results depends on mathematic formulae requiring a special calculator or mathematic tables. This causes difficulties and errors. A simplified system for interpretation of INRs with the range of thromboplastins widely used in North America is therefore presented, which obviates the need for mathematic procedures for the derivation of INR equivalents. It should thus facilitate the application of the INR system and of safer therapeutic ranges.     

Purification and characterization of IgG immunoconglutinins from patients with systemic lupus erythematosus: implications for a regulatory function.

The levels of IgG immunoconglutinins in plasma from patients with rheumatoid arthritis, systemic lupus erythematosus and primary biliary cirrhosis were monitored by ELISA. High levels of IgG immunoconglutinins were found mainly in plasma from patients with systemic lupus erythematosus. These immunoconglutinins bound to microtitre plate-fixed C3, C3b and C3c but poorly to C3d. This binding was inhibited by particle-bound C3b and iC3b but not by the corresponding soluble fragments. Furthermore, Western blot analysis revealed no immunoconglutinin-binding to reduced C3 peptides and no binding was shown to soluble C3 alpha and beta chain by ELISA. IgG immunoconglutinins were purified from three plasma specimens by affinity chromatography on activated thiol sepharose ATS/C3 fragments. Two immunoconglutinin preparations that preferentially recognize ATS-C3b, inhibited C5-convertase function by 50-100% while one immunoconglutinin that recognized ATS-C3d,g had no effect. The two former immunoconglutinins also inhibited all three factor I cleavages in C3 alpha chain but the latter inhibited only the third cleavage. None of the immunoconglutinins affected the binding of complement-coated anti-BSA/BSA complexes to CR1 (CD35) on human erythrocytes, but the two immunoconglutinins that inhibited all factor I cleavages also inhibited the factor I-induced release of anti-BSA/BSA complexes from CR1. The results show that immunoconglutinins recognize specific epitopes on bound C3 fragments and that they are able to modulate C3-mediated functions.     

Overweight and obesity among patients attending a Nigerian oral surgery clinic: implications for oral surgical practice in Nigeria

Aim

To determine the prevalence of overweight and obesity among patients attending oral and maxillofacial outpatient clinic of the Lagos University Teaching Hospital, Nigeria; and discuss the clinical and surgical implications that obesity has on the delivery of oral and maxillofacial surgical and anaesthetic care.

Methods

Consecutive patients presenting to the oral and maxillofacial surgery outpatient clinic at the Lagos University Teaching Hospital, Nigeria over a 4-month period (May–August 2004) were screened for age, sex, height and weight. All of the patients were treated for dentoalveolar surgical procedures (routine and surgical extractions), incisional and excisional biopsies, and enucleation under local anaesthesia.

Results

The BMIs of the studied patients ranged from 16.7 to 39.8 kg/m², with a mean of 24.6 ± 4.5 kg/m². Prevalence of excess weight was 39.1%. Thirty-one (11.4%) patients were obese and 75 (27.7%) patients were overweight. A significant difference was observed in the BMIs of male and female patients (P=0.000). The age groups < 30 years had mean BMIs that were considered normal; whereas other age groups above 30 years had mean BMIs that were considered overweight. Prevalence of obesity increases with increasing age. Obese individuals were seen in all the age groups except those < 20 years.

Conculsions

The prevalence of excess weight (overweight and obesity) in patients presenting in the studied oral and maxillofacial outpatient setting was 39.1%. Oral and maxillofacial surgeon needs to be aware of obesity-/overweight-related medical and surgical issues and take them into consideration when treating these patients.     

Long-term monitoring of patients with infantile-onset Pompe disease on enzyme replacement therapy using a urinary glucose tetrasaccharide biomarker

PurposeTo investigate the correlation of the urinary glucose tetrasaccharide, Glcα1-6Glcα1-4Glcα1-4Glc, (Glc₄) with skeletal muscle glycogen content and the long-term clinical response to enzyme replacement therapy with recombinant human acid alpha glucosidase in infantile Pompe disease.MethodsEighteen patients, ≤6 months old, were enrolled in a clinical trial of enzyme replacement therapy for up to 142 weeks. Urinary Glc₄, skeletal muscle glycogen, and other clinical and laboratory assessments were made at baseline and at regular intervals. Urinary Glc₄ was determined using an isotope-dilution tandem mass spectrometric assay. The clinical response to treatment was defined according to the motor function response. Trends in urinary Glc₄ were correlated with the clinical response and compared with serum enzyme markers of skeletal muscle damage, creatine kinase, aspartate aminotransferase, and alanine aminotransferase.ResultsUrinary Glc₄, in contrast to the serum markers, correlated closely with skeletal muscle glycogen content and with the clinical response. Patients with the best response to treatment maintained the lowest levels of Glc₄ throughout the trial.ConclusionThe results from this study support the use of urinary Glc₄ for monitoring patients with infantile-onset Pompe disease on therapy.     

Enzyme-linked immunoassay using recombinant trans-sialidase of Trypanosoma cruzi can be employed for monitoring of patients with Chagas' disease after drug treatment

trans-Sialidase is an enzyme present on the surface of Trypanosoma cruzi and is an important antigen recognized by sera from patients with Chagas' disease. In the present study we investigated whether the benznidazole treatment of patients with Chagas' disease induced changes in the reactivity of serum toward a recombinant form of trans-sialidase in order to develop an assay for monitoring of patients after treatment for Chagas' disease, which is needed at Chagas' disease control centers. By using an enzyme-linked immunosorbent assay containing a recombinant protein corresponding to the catalytic domain of trans-sialidase, we found that the antigen had a high specificity for sera from untreated patients with Chagas' disease. Sera from healthy individuals or patients with active visceral leishmaniasis minimally cross-reacted with the antigen. Anti-trans-sialidase immunoglobulin was detected in 98% of 151 untreated patients with Chagas' disease. Of these, 124 patients were treated for 60 days with benznidazole (5 mg/kg of body weight/day), and their sera were assayed for reactivity with the recombinant trans-sialidase. By using this methodology, three groups of patients could be established. The first group (60 patients), which was considered to have been successfully treated, showed no reactivity after treatment. The second group (46 patients) still showed signs of infection, and after treatment their sera recognized trans-sialidase, but with reduced titers. The third group (18 patients) was considered to be resistant to drug treatment, and their sera presented identical reactivities before and after treatment. These results suggest that determination of the absence of antibodies to recombinant trans-sialidase in treated patients by the present assay is indicative of treatment success, while the presence of antibodies may indicate the persistence of infection. Therefore, this method may be useful for the diagnosis and monitoring of patients undergoing benznidazole treatment.