Katharina Madlener

Use of Heparin during Cardiopulmonary Bypass in Patients with a History of Heparin-Induced Thrombocytopenia

To the Editor: Patients with heparin-induced thrombocytopenia are at high risk for thromboembolic complications. Heparin-induced thrombocytopenia is caused by heparin-related and platelet-activatin...

MONITORING OF RECOMBINANT HIRUDIN: ASSESSMENT OF A PLASMA-BASED ECARIN CLOTTING TIME ASSAY

Assay conditions of a plasma-based ecarin clotting time (ECT) were evaluated and the precision of the ECT in monitoring plasma levels of r-hirudin assessed. The snake venom enzyme ecarin converts prothrombin to meizothrombin possessing only weak coagulant but strong esterase activity. In r-hirudin containing plasma samples, meizo thrombin is rapidly neutralized by r-hirudin resulting in a dose-dependent prolongation of the clotting times. Among the different assay conditions tested, addition of 50 microliters of ecarin (4 U/ml) to 100 microliters of undiluted citrate-anticoagulated plasma gave optimal results with respect to precision and reproducibility. The measuring range of the ECT performed in this way is about 0.02-5.0 micrograms/ml r-hirudin. In vitro studies performed on r-hirudin-spiked plasma samples of 50 healthy individuals demonstrate remarkably low interindividual differences in r-hirudin responsiveness as indicated by CV-values below 5% and 7% at r-hirudin concentrations between 0-3 micrograms/ml and 4-5 micrograms/ml, respectively. The specificity for r-hirudin of the ECT is further demonstrated by the strong correlation (r = 0.94) between the results of a chromogenic assay and the ECT-measured r-hirudin concentrations obtained on 67 ex vivo blood samples. Depending on the concentration of r-hirudin the ECT is sensitive to plasma levels of prothrombin. In the absence of r-hirudin the critical prothrombin concentration was found to be 20% but increasing to 60% in the presence of 2.0 micrograms/ml r-hirudin. A fibrinogen concentration of 50 mg/dl was found to be the minimal concentration independent of the r-hirudin concentration. The precision of the ECT in measuring plasma levels of r-hirudin is not influenced by treatment with heparin, aprotinin or oral anticoagulants. The data demonstrate that the ECT is a rapid and easily perfor mable clotting assay which allows accurate measurement of r-hirudin plasma levels. ECT-monitored hirudin treatment will help to establish optimal dose regimens that are more efficacious but still as safe as heparin.

Therapie mit Blutkomponenten und Plasmaderivaten in der Geburtshilfe

ZusammenfassungAkute Blutungen und angeborene oder erworbene Gerinnungsstörungen stellen in der Geburtshilfe die Hauptindikationen für die Therapie mit zellulären und plasmatischen Blutkomponenten dar. In der akuten Blutungssituation, in der Erythrozytenkonzentrate und Frischplasma substituiert werden müssen, ist ein regelmäßiges Gerinnungsmonitoring, das neben den Globaltesten, der Bestimmung der Thrombozytenanzahl auch die Fibrinogen- und Faktor-V-Bestimmung umfassen sollte, eine wichtige Voraussetzung um begleitende oder entstehende Gerinnungsstörungen frühzeitig zu erkennen. In Abhängigkeit von der jeweiligen klinischen Symptomatik und der bestehenden Grunderkrankung ist dann eine gezielte Substitution mit Frischplasma, Thrombozyten und gereinigten Gerinnungsfaktoren möglich. Im folgenden Kapitel werden für die häufigsten hämostaseologischen Störungen in der Geburtshilfe entsprechende Diagnose- und Therapieschemata besprochen. Die Gliederung orientiert sich dabei an der jeweiligen klinischen Situation und den laboranalytisch meßbaren Gerinnungsveränderungen.

Red blood cells treated with the amustaline (S-303) pathogen reduction system: a transfusion study in cardiac surgery: AMUSTALINE RBCs IN CARDIAC SURGERY

Nucleic acid–targeted pathogen inactivation technology using amustaline (S‐303) and glutathione (GSH) was developed to reduce the risk of transfusion‐transmitted infectious disease and transfusion‐associated graft‐versus‐host disease with red blood cell (RBC) transfusion.

Ultrasound Destruction of Air Microemboli as a Novel Approach to Brain Protection in Cardiac Surgery

OBJECTIVE Evaluation of a novel approach to eliminate air microemboli from extracorporeal circulation via ultrasonic destruction. DESIGN In vitro proof-of-concept study. SETTING Research laboratory. PARTICIPANTS None. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS An extracorporeal circulation device was filled with human blood circulating at 3 L/min. Air bubbles were injected into the system. For bubble destruction, the blood in the tubing system was repeatedly insonated for 3 minutes using a therapeutic 60-kHz device, with variation of intensity and duty cycle settings, ranging from 0.2 W/cm² to 1.0 W/cm² and from duty cycle 60% to continuous wave (CW). Number and diameter of air microemboli were counted upstream and downstream of the ultrasound device by a 2-channel microemboli Doppler detector. For safety assessment, circulating blood was insonated continuously for 2 hours at 0.8 W/cm² CW and compared with circulation without insonation; and standard blood parameters were analyzed. Without treatment, 1,313 to 1,580 emboli were detected upstream, diameter ranging between 10 and 130 μm. Ultrasound treatment eliminated up to 87% of all detected bubbles in cw application (p<0.01) and showed comparable effects at intensities from 0.4 W/cm² to 1.0 W/cm² cw. Bubbles sized>15 μm almost were eliminated completely (p<0.001). Pulsed wave application rendered inferior results (p>0.05). No relevant changes of blood parameters were observed compared with control circulation. CONCLUSIONS Ultrasound destruction of air emboli is a very efficient method to reduce number and size of emboli. Within the limits of safety assessment, the authors could not detect relevant side effects on standard blood parameters.