[Patient self-management of oral anticoagulation]. / Die Patienten-Selbstkontrolle der oralen Antikoagulation.

Self management of oral anticoagulation (OAC) has been demonstrated to improve the quality of oral anticoagulation as assessed by the percentage of INR values within the individual target range. There were tendentially less bleeding and thromboembolic complications in the group with self management of OAC. The capillary INR values of the only available monitor in Switzerland (CoaguChek, Roche Diagnostics, AG) correlated good with venous INR. Thus, self management of OAC may be a valuable alternative to conventional anticoagulation in selected and motivated patients on long term anticoagulation.

Increased fibrin monomer plasma concentration in stable coronary artery disease in patients without oral anticoagulation.

Blood coagulation has been shown to play a role in the pathogenesis of local thrombus formation in coronary arteries. Increased plasma concentrations of thrombin activation markers such as fibrin monomers (FM) indicate coagulation activation. Therefore, we investigated FM plasma levels in 194 patients (127 nonanticoagulated and 67 anticoagulated) with stable coronary artery disease (CAD) and in 96 healthy controls. FM levels were significantly higher (P<0.0001) in nonanticoagulated patients compared with healthy controls, whereas anticoagulated patients showed significantly lower (P<0.0001) FM levels, respectively. FM levels above 0.50 mg/ml were associated with an odds ratio (OR) of 3.0 (95% confidence interval (CI), 1.7--5.5) for the presence of stable CAD in nonanticoagulated patients. However, the association lost significance after correction for possible confounders such as age, body mass index, total cholesterol, fibrinogen, sex, smoking, arterial hypertension and diabetes mellitus. In conclusion, we found elevated FM plasma levels in nonanticoagulated patients as compared with healthy controls. Elevated FM plasma levels were associated with an OR of 3.0 for the presence of stable CAD in nonanticoagulated patients.

Rapid D-dimer testing and pre-test clinical probability in the exclusion of deep venous thrombosis in symptomatic outpatients.

We assessed the performance of three rapid D-dimer tests (Auto Dimertest, VIDAS and Tinaquant) in combination with a pretest clinical probability model for deep venous thrombosis (DVT) in 106 consecutive outpatients with suspected DVT. Contrast venography or colour-coded duplex ultrasonography demonstrated the presence of DVT in 47 patients (14 distal DVT and 33 proximal DVT). First, we assessed the accuracy indices for different cut-off levels of the rapid D-dimer tests. Sensitivity was found to be 97.9-100%, negative predictive value (NPV) was 96.3-100%, and the exclusion rate was 24.5-31.1%. Next, the patients were grouped according to the pre-test clinical probability model in categories with low, moderate or high probability. In patients with a low pre-test probability, DVT would have been directly ruled out and the patients would not have undergone further investigations. In patients with a moderate probability, D-dimer testing and, in the case of a positive result, objective testing would have been performed and, in the case of a negative result, they would have been ruled out of having DVT. Patients with high probability would directly have undergone objective tests for DVT. The combination with the pre-test clinical probability model improved the exclusion rate (43.5-44.6%), whereas sensitivity (97.5-100%) and NPV (97.6-100%) remained roughly unchanged. The combination of rapid D-dimer tests with a pre-test clinical probability model may help to reduce unnecessary work-up in patients with suspected DVT.

[Patient self-monitoring of oral anticoagulation with CoaguChek]. / Patienten-Selbstkontrolle der oralen Antikoagulation mit CoaguChek.

We investigated the feasibility, quality and safety of patient self-control of oral anticoagulation. The patients were selected by their physicians on the basis of criteria such as compliance, skills and motivation. After theoretical and practical training they self-monitored and self-adjusted their anticoagulant dosage for 6 months by weekly self-measurement of their INR values using a capillary whole blood prothrombin time monitor (CoaguChek). Venous INR measurements once a month served as quality control. There were 51 study participants, who performed a median 5 INR measurements per month. 75.8% of all registered INR values were within the recommended individual INR target ranges. The coefficient of correlation between capillary (y) and venous (x) INR values was r = 0.87 (regression analysis y = 1.0 x -0.2). The concordance of capillary and venous INR values was 80% with respect to the individual INR target ranges. There were 5 minor bleeding episodes and no overt thromboembolic recurrences during the study period. In conclusion, the study demonstrated that patient self-control of oral anticoagulation is feasible and achieves a high percentage of INR values within the recommended target ranges. Therefore, self-control of oral anticoagulation can be offered to skilled and motivated patients as an alternative to physician-guided antiocogulation. However, specific training of these selected patients is necessary.

C1-Esterase inhibitor: an anti-inflammatory agent and its potential use in the treatment of diseases other than hereditary angioedema.

C1-esterase inhibitor (C1-Inh) therapy was introduced in clinical medicine about 25 years ago as a replacement therapy for patients with hereditary angioedema caused by a deficiency of C1-Inh. There is now accumulating evidence, obtained from studies in animals and observations in patients, that administration of C1-Inh may have a beneficial effect as well in other clinical conditions such as sepsis, cytokine-induced vascular leak syndrome, acute myocardial infarction, or other diseases. Activation of the complement system, the contact activation system, and the coagulation system has been observed in these diseases. A typical feature of the contact and complement system is that on activation they give rise to vasoactive peptides such as bradykinin or the anaphylatoxins, which in part explains the proinflammatory effects of either system. C1-Inh, belonging to the superfamily of serine proteinase inhibitors (serpins), is a major inhibitor of the classical complement pathway, the contact activation system, and the intrinsic pathway of coagulation, respectively. It is, therefore, endowed with anti-inflammatory properties. However, inactivation of C1-Inh occurs locally in inflamed tissues by proteolytic enzymes (e.g., elastase) released from activated neutrophils or bacteria thereby leading to increased local activation of the various host defense systems. Here we will give an overview on the biochemistry and biology of C1-Inh. We will discuss studies addressing therapeutic administration of C1-Inh in experimental and clinical conditions. Finally, we will provide an explanation for the therapeutic benefit of C1-Inh in so many different diseases.

Continuous infusion of von Willebrand factor and factor VIII after elective heart surgery in a 12-year-old girl with von Willebrand disease type 3.

The continuous infusion of von Willebrand factor (VWF) in a 12-year-old girl with type 3 von Willebrand disease is described. The patient had elective heart surgery with cardiopulmonary bypass for closure of her atrial septum defect. The surgical procedure lasted 3 h. A presurgical bolus followed by a postoperative continuous infusion of factor VIII/VWF concentrates was administered. During the continuous infusion of clotting factors, stable plasma levels of hemostasis and avoidance of dangerously low levels of factor concentrates were achieved. No peri- or postsurgical complications occurred. Continuous infusion of clotting factors allows constant and hemostatic factor concentrations to be maintained with the possibility of dose titration and adjustment.

[D-dimer determination in suspected deep venous thrombosis or lung embolism]. / D-Dimer-Bestimmung bei Verdacht auf tiefe Venenthrombose oder Lungenembolie.

Cleavage of crosslinked fibrin by the fibrinolytic enzyme plasmin leads to the formation of fibrin degradation products, among them D-dimers. D-Dimer can easily be measured in plasma or in whole blood by means of monoclonal antibodies directed against epitopes of the D-dimer fragment. Elevated plasma levels of D-dimers are characteristic for patients with venous thromboembolism (DVT, PE), but occur also in patients with infectious diseases, malignant neoplasms and heart failure. Given the high sensitivity of ELISA D-dimer assays with respect to venous thromboembolism it is possible to reliably rule out DVT or PE when the plasma concentration of D-dimer is below the cut-off level. Thus, it is possible to rule out DVT in about 30% of outpatients with suspected venous thromboembolism by the measurement of D-dimer-concentration with a validated assay avoiding further diagnostic procedures.

[Activation of plasma cascade systems in sepsis: role of C1 inhibitors]. / Aktivierung der plasmatischen Kaskadensysteme bei Sepsis: Rolle von C1-Inhibitor.

During sepsis the complement system, the contact activation system and the coagulation cascade are activated. Activation of these plasmatic cascades contributes to the development of multiple organ failure and the high mortality rate of severe sepsis and septic shock. C1-inhibitor is the main inhibitor of the classical pathway of the complement system (C1s and C1r), of the contact activation system (factor XIIa and kallikrein) and of the intrinsic pathway of coagulation (factor XIa). During sepsis, C1-inhibitor is proteolytically inactivated. The increase of inactivated C1-inhibitor in plasma correlates positively with mortality in septic patients. C1-inhibitor substitution has been shown to reduce the mortality in experimental animals with severe sepsis or septic shock. Only a few cases of C1-inhibitor substitution in patients with severe sepsis or septic shock have been reported. C1-inhibitor has been shown to attenuate the activation of the complement system and the contact activation system and to improve hypotension. Based on this convincing pathophysiological concept and the results of the animal studies, we initiated the "Bernese C1-inhibitor study", a randomised double-blind and placebo-controlled pilot study involving administration of C1-inhibitor to patients with severe sepsis or septic shock. If the results of this pilot study confirm the results of the reports mentioned above, they will serve as a base for larger multicentre studies.

Performance of a new fibrin monomer assay to exclude deep vein thrombosis in symptomatic outpatients.

UNLABELLED: In this study we prospectively assessed the reliability of a new fibrin monomer assay in 106 outpatients with clinically suspected deep venous thrombosis of the lower limb. According to the results of the objective tests and using different cut-off points we calculated the sensitivity, specificity and negative predictive value of the fibrin monomer assay. The prevalence of deep vein thrombosis was 44.3% (31.1% proximal, 13.2% distal). Using a cut-off level of plasma fibrin monomer of 3.5 microg/ml, a sensitivity, specificity and negative predictive value of 100% (95% CI: 94-100%), 35.6% (95% CI: 23-48%) and 100% (95% CI: 86-100%), respectively, were obtained. The exclusion rate was 19.8% (95% CI: 12-27%) of all referred patients. These accuracy indices compared favourably with the respective results of a routine D-dimer ELISA used for comparison. CONCLUSION: This new fibrin monomer assay appears to be a reliable method for the exclusion of deep vein thrombosis in symptomatic outpatients.

Two consecutive pregnancies and deliveries in a patient with von Willebrand's disease type 3.

Pregnancy and delivery are critical events in women with von Willebrand's disease type 3. Prophylactic treatment for delivery and early postpartum period is recommended. Vaginal delivery is considered safe. However, experience is based on rare case reports. We report the management of two pregnancies and successful deliveries in a woman with von Willebrand's disease type 3.