Herbert Watzke

Performance evaluation of the new CoaguChek XS system compared with the established CoaguChek system by patients experienced in INR-self management

The aim of the study was to analyze the concordance of INR values obtained by educated lay users with those obtained by professionals and to determine the imprecision of the new system. The new CoaguChek XS system was tested in a user study over six weeks at four study centres in Austria, Denmark and Germany. Seventy-five patients receiving oral anticoagulant therapy were enrolled in the study. The INR results in capillary whole blood taken by professionals and by patients using the CoaguChek XS system were similar, and the mean relative bias was <1%. The imprecision of the CoaguChek XS system calculated from duplicate testing is low (<6%) and slightly better than for the established CoaguChek S system. The INR results measured during the home testing phase correlated quite well between the established CoaguChek S system and the new CoaguChek XS system with a mean bias of 0.14 INR. This is a remarkably low bias taking into consideration that more than 30 different test strip lots were applied. A questionnaire was filled out by all patients to assess their personal impression. It revealed that patients were very satisfied with the new system and found it easy to operate. The results demonstrate that the agreement between professional and patient INR results for the new CoaguChek XS system was excellent and that INR values can be determined by lay users as well as by professionals. The instrument is very well accepted by the patients and their satisfaction even increased after four weeks practice at home.

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).

The Decanucleotide Polymorphism in the Factor VII Promoter Predicts Factor VII Plasma Levels but not the Risk of Acute Coronary Syndromes

It is known from large epidemiological studies that the elevation of coagulation factor VII in plasma is an independent risk factor for acute coronary syndromes. The level of factor VII is influenced by polymorphic sites in the factor VII gene. However, data on the association of such polymorphisms with the risk of acute coronary syndromes are conflicting. A decanucleotide insertion/deletion polymorphic site has been described in the promoter of the factor VII gene that leads to a dramatic change in the plasma factor VII levels. We therefore analyzed the association of this polymorphism with the risk of acute coronary syndromes in a case-control study. Included in the study were 111 patients with angiographically documented acute coronary syndromes and 108 age- and sex-matched individuals from the same geographic area without signs or symptoms of coronary heart disease. The presence or absence of the decanucleotide stretch at position −323 in the promoter of factor VII was monitored using a polymerase chain reaction (PCR)–based restriction technique. The prevalence of the genotype with the homozygous deletion was similar in the patients with acute coronary syndromes (79.2%) and in the control patients (79.6%). There was a non-significant trend toward a higher prevalence of the homozygote deletion in patients with premature acute coronary syndromes (77.4%) compared with an age-matched subgroup of the control patients (67.5%) (odds ratio [OR] 1.6, confidence interval [CI] 0.95, 0.61–3.93). Thus, we could not find a significant association of the ocurrence of acute coronary events with the insertion/deletion polymorphism in factor VII.

Elevated activation markers of coagulation in patients undergoing orthognathic surgery

Surgery is associated with a variable but increased incidence of postoperative venous thromboembolism (VTE). The risk of VTE after orthognathic surgery is unknown. Recently developed assays for activation markers of blood coagulation allow the detection of a prethrombotic state and may thus help to identify surgical procedures with a risk of postoperative VTE. The pre- and postoperative levels of thrombin-antithrombin complex (TAT) and prothrombin fragment 1+2 (F1+2) were studied in ten patients undergoing orthognathic surgery. Mean levels of TAT and F1+2 were within the normal range preoperatively (TAT:2.6+1.0 microg/L, F1+2:0.8+0.2 nmol/L). A significant increase in both parameters occurred postoperatively (TAT:21.8+21.4 microg/L, P<0.005; F1+2:1.3+0.4, P<0.02). No increase was observed in a control group (n=13) consisting of patients undergoing minor surgical procedures in general anesthesia. Our study shows that a marked activation of the coagulation cascade occurs during orthognathic surgery which warrants further studies on the true incidence of postoperative VTE in patients undergoing orthognathic surgery.

Clinical significance of gene-diagnosis for defects in coagulation factors and inhibitors.

ZusammenfassungDie Aufklärung der cDNA-Sequenz der Gerinnungsfaktoren und ihrer Inhibitoren hat die Grundlage zur Erforschung der genetischen Ursachen der familiären Blutungsneigung und der familiären Thromboseneigung geschaffen. Der größte Teil dieser Defekte hat eine massive klinische Konsequenz im Sinne einer schweren Blutungsneigung oder einer Prädisposition zu venösen und arteriellen thromboembolischen Erkrankungen. Unbeschadet dieser Konsequenzen ist eine DNA-Analyse zum Nachweis der Blutungs-oder Thromboseneigung nur in wenigen Fällen klinisch notwendig. Gegenstand dieses Reviews ist deshalb die Beschreibung jener Situationen, in denen eine DNA-Analyse von Relevanz in der klinischen Betreuung von Patienten mit Hämophilie oder Thrombophilie ist.SummarycDNA sequences of all known coagulation factors and inhibitors of coagulation have been described and an enormous number of disease generating mutations in these factors has been found by genetic analysis of affected families. The vast majority of these defects have severe clinical consequences such as spontaneous bleeding or predisposition to venous thrombosis and pulmonary embolism. While all the genetic defects described so far cause disease, or at least represent a risk factor for diseases such as bleeding or thrombosis, only a minority of these conditions actually need DNA analysis to be detected and/or treated properly. The purpose of this review is therefore to describe clinical situations in which the knowledge of the underlying genetic defect is important for decision making in patients with inherited hemophilia or thrombophilia.

Management der oralen Antikoagulation bei invasiven Eingriffen

SummaryTemporary interruption of oral anticoagulation to perform invasive procedures is a frequently occurring medical problem. There are only a few studies available on the optimal clinical approach in this situation. The published clinical studies and guidelines are summarized.ZusammenfassungDie Notwendigkeit der Unterbrechung der oralen Antikoagulation zur Durchführung invasiver Eingriffe stellt ein häufiges klinisches Problem dar. Zur optimalen Vorgangsweise in dieser Situation liegen nur wenige klinische Studien und einige Empfehlungen internationaler Fachgesellschaften vor. Im Folgenden werden die Ergebnisse der Studien und die daraus abgeleiteten Empfehlungen dargelegt.

Patientenverfügung aus ärztlicher Sicht

Mit dem Wirksamwerden des neuen osterreichischen Patientenverfugungs-Gesetzes sind Arzte nun in zwei Situationen, die vollig verschiedene Anforderungen an sie stellen, mit Patientenverfugungen konfrontiert. Zum einen sind sie wie bisher als Ausfuhrende von vorliegenden Verfugungen gefordert. Hier ist es allerdings durch die neue Gesetzeslage, die ja genau auf eine geanderte Rolle der Arzte in dieser Situation abgezielt hat, zu wesentlichen Veranderungen gekommen. Zum anderen ist nach der neuen Gesetzeslage auch die Mitwirkung von Arzten nicht nur an der Ausfuhrung, sondern auch an der Erstellung einer Patientenverfugung unabdingbare Voraussetzung fur ein gesichertes Wirksamwerden einer Verfugung im Anlassfall. Es werden deshalb im Folgenden beide „Rollen“ von Arzten und deren Interaktion dargelegt.