The quality of oral anticoagulation before, during and after a period of patient self-management.

The study analyzes the quality of anticoagulation during a 3-year follow-up on patients who were treated by an anticoagulation clinic (ACS) for 1 year (Phase I), performed weekly self-management of anticoagulation (PSM) after a specific training for another year (Phase II) and finally returned to be treated by the anticoagulation clinic (ACS) for a third year (Phase III). The mean fraction of INR values within therapeutic target range was higher in Phase II (0.69 +/- 0, 11) compared to Phases I (0.40 +/- 0.20) and III (0.56 +/- 0.18; p < 0.05). Time spent in therapeutic target range was higher in Phase II (0.70 +/- 0.10) compared to Phases I (0.43 +/- 0.25) and III (0.60 +/- 0.17; p < 0.05). Mean square deviation from target value was lower in Phase II (0.39 +/- 0.17) compared to Phases I (0.81 +/- 0.44) and III (0.64 +/- 0.39, p = 0.05). Thus, the quality of anticoagulation during Phase II (PSM) was significantly better compared to Phases I (ACS) and III (ACS) in all endpoints tested. This shows that the quality of oral anticoagulation deteriorates again if patient self-management is stopped and patients return to conventional treatment. Furthermore, the quality of anticoagulation was better in Phase III (post-PSM) compared with Phase I (pre-PSM) although the type of treatment was identical in both phases (ACS). This suggests that the increased patient empowerment and enhanced compliance acquired during PSM (Phase II) might have a positive impact on the quality of anticoagulation, even when patients return to the conventional treatment (ACS).

A prospective controlled trial comparing weekly self-testing and self-dosing with the standard management of patients on stable oral anticoagulation.

Oral anticoagulant therapy requires frequent laboratory controls of its intensity to assure therapeutic efficacy and to prevent potentially life threatening adverse events. It is generally assumed, that increasing the frequency of testing would lead to a better control of anticoagulation. We tested this hypothesis in a prospective controlled trial comparing weekly self-testing and self-dosing (self management) with the standard-management of these patients in an anticoagulation clinic. Only patients with stable anticoagulation were included into the study. We recorded 2733 weekly determinations of the intensity of anticoagulation (INR) in 49 patients on self-testing and self-dosing and 539 determinations of the INR in 53 patients on standard-management. Two intensities of anticoagulation were used in each group: a target INR of 3.5 for patients with artificial heart valves (target range: 2.5-4.5) and a target INR 2.5 (target range: 2.0-3.0) for patients with atrial fibrillation or venous thromboembolism. The deviation from the target INR, the fraction of INR determinations within the preset therapeutic range and the difference between the target INR and the actually achieved mean INR were the three major endpoints of the study. The mean deviation from the target INR was smaller in the groups of patients on self-management compared to the patients on standard-management. Individual deviations were significantly (p <0.0001) dependent on the type of management in interaction with the treatment intensity in a general linear model. Patients on weekly self-testing and self-dosing had more INR values within the therapeutic range than patients on standard-management (86.2% vs. 80.1% at INR range 2.5-4.5; 82.2 vs. 68.9 at INR range 2.0-3.0). The achieved mean INR was almost identical with the target INR in the patients on self-management but was significantly (p <0.005) below the target INR in the high intensity anticoagulation group on standard-management (target INR:3.5; achieved mean INR: 3.19; CI 0.95: 3.05-3.34). Our data show, that weekly self-testing and self-dosing leads to a better control of anticoagulation than standard treatment in an anticoagulation clinic.

Factor X Frankfurt I: molecular and functional characterization of a hereditary factor X deficiency (Gla+25 to Lys).

A family with hereditary factor X deficiency is presented. One member, a 25-year-old man, showed a mild bleeding tendency. His factor X activity (extrinsic: 56%; intrinsic: 55%; Russell's viper venom: 57%) and his level of circulating factor X antigen (55% of normal) were markedly reduced. Analysis of his factor X gene revealed a single point mutation within exon II resulting in the substitution of +25 Gla (GAA) by Lys (AAA). The mutation was determined by gene analysis to be heterozygous in this patient, his mother and one of his brothers. Clotting assays of factor X purified from the plasma of the index patient revealed an activity of 89% of normal upon activation with Russell's viper venom, 77% of normal in the intrinsic and 81% of normal in the extrinsic coagulation pathway. The mutation responsible for the substitution of Lys for Gla+25 was introduced into an expression plasmid containing a wild type factor X cDNA and expressed in a mammalian cell line. Factor X antigen levels in the cell lysates and in the supernatant were identical in the mutant and wild type constructs. The specific activity of the factor X expressed from the mutant construct was 3% compared with the wild type construct. These data demonstrate that the substitution of Lys for Gla+25 results not only in a reduced level of factor X in the affected family members, but also in a substantial loss of specific factor X activity.

Effect of treatment with activated prothrombin complex concentrate (FEIBA) on factor VIII-antibody level.

The influence of treatment with an activated prothrombin complex preparation (FEIBA) on the antibody level was studied in 10 haemophiliacs with an antibody to factor VIII. The antibody level was observed to rise at least once in five patients, while in the remaining five patients no rise occurred. In all, 6 out of 31 treatments were followed by an anamnestic rise of the antibody level, corresponding to 19.4%. A rise of the inhibitor level following FEIBA treatment is likely to occur in patients who show a marked antibody rise after factor VIII treatment (good responders), but have a low antibody level at the time of treatment. High doses of FEIBA and simultaneous of red cells may also enhance the likelihood of an anamnestic response. Stimulation of antibody production is probably due to the presence of small amounts of factor VIII in this preparation.