Kathrin Hamilton

In vitro comparison of dabigatran, unfractionated heparin, and low-molecular-weight heparin in preventing thrombus formation on mechanical heart valves

INTRODUCTION Lifelong oral anticoagulation (OAC) therapy is required for the prevention of thromboembolic events after implantation of an artificial heart valve. Thromboembolism and anticoagulant-related bleedings account for approximately 75% of all complications experienced by heart valve recipients (2-9% of patients per year). The present study investigated the efficacy of dabigatran, a new direct thrombin inhibitor for oral use, as compared to unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) in preventing thrombus formation on mechanical heart valves in vitro. MATERIAL AND METHODS Blood (230 ml) from healthy young male volunteers was anticoagulated either by dabigatran (1 micromol/l), UFH (150 IU), or LMWH (100 IU). Mechanical heart valve prostheses were placed in an in vitro thrombosis tester and exposed to the anticoagulated blood samples under continuous circulation at a rate of 75 beats per minute. RESULTS In whole blood with no anticoagulant, the apparatus completely clotted in 15-20 minutes. When blood was treated with dabigatran, the mean thrombus weight was 164+/-55 mg, in the UFH group 159+/-69 mg, and in the LMWH group 182+/-82 mg (p-value: 0.704). Electron microscopy showed no significant difference in thrombus formation in any group. CONCLUSIONS Dabigatran was as effective as UFH and LMWH in preventing thrombus formation on mechanical heart valves in our in vitro investigation. Thus, we hypothesize that dabigatran etexilate might potentially be a useful and competitive orally administered alternative to UFH and LMWH for recipients of alloplastic heart valve prostheses.

Argatroban and bivalirudin compared to unfractionated heparin in preventing thrombus formation on mechanical heart valves: Results of an in-vitro study

Prevention of valve thrombosis in patients after prosthetic mechanical heart valve replacement and heparin-induced thrombocytopenia (HIT) is still an open issue. The aim of the present in-vitro study was to investigate the efficacy of argatroban and bivalirudin in comparison to unfractionated heparin (UFH) in preventing thrombus formation on mechanical heart valves. Blood (230 ml) from healthy young male volunteers was anticoagulated either by UFH, argatroban bolus, argatroban bolus plus continuous infusion, bivalirudin bolus, or bivalirudin bolus plus continuous infusion. Valve prostheses were placed in a newly developed in-vitro thrombosis tester and exposed to the anticoagulated blood samples. To quantify the thrombi, electron microscopy was performed, and each valve was weighed before and after the experiment. Mean thrombus weight in group 1 (UFH) was 117 + 93 mg, in group 2 (argatroban bolus) 722 + 428 mg, in group 3 (bivalirudin bolus) 758 + 323 mg, in group 4 (argatroban bolus plus continuous infusion) 162 + 98 mg, and in group 5 (bivalirudin bolus plus continuous infusion) 166 + 141 mg (p-value <0.001). Electron microscopy showed increased rates of thrombus formation in groups 2 and 3. Argatroban and bivalirudin were as effective as UFH in preventing thrombus formation on valve prostheses in our in-vitro investigation when they were administered continuously. We hypothesise that continuous infusion of argatroban or bivalirudin are optimal treatment options for patients with HIT after mechanical heart valve replacement for adapting oral to parenteral anticoagulation or vice versa.

NMR and MRI of Blood-Dissolved Hyperpolarized Xe-129 in Different Hollow-Fiber Membranes

Magnetic resonance of hyperpolarized (129)Xe has found a wide field of applications in the analysis of biologically relevant fluids. Recently, it has been shown that the dissolution of hyperpolarized gas into the fluid via hollow-fiber membranes leads to bubble-free (129)Xe augmentation, and thus to an enhanced signal. In addition, hollow-fiber membranes permit a continuous operation mode. Herein, a quantitative magnetic resonance imaging and spectroscopy analysis of a customized hollow-fiber membrane module is presented. Different commercial hollow-fiber membrane types are compared with regard to their (129)Xe dissolution efficiency into porcine blood, its constituents, and other fluids. The presented study gives new insight into the suitability of these hollow-fiber membrane types for hyperpolarized gas dissolution setups.

Consequences Arising From Elevated Surface Temperatures on Human Blood

Heat in blood pumps is generated by losses of the electrical motor and bearings. In the presented study the influence of tempered surfaces on bulk blood and adhesions on these surfaces was examined. Titanium alloy housing dummies were immersed in 25 mL heparinized human blood. The dummies were constantly tempered at specific temperatures (37-45 °C) over 15 min. Blood samples were withdrawn for blood parameter analysis and the determination of the plasmatic coagulation cascade. The quantities of adhesion on surfaces were determined by drained weight. Blood parameters do not alter significantly up to surface temperatures of 45 °C. In comparison to the control specimen, a drop in the platelet count can be observed, but is not significantly temperature dependent. The mean mass of adhesions at 41 °C increased up to 66% compared to 37 °C. Thus, heat generated in electrical motors and contact bearings may influence the amount of adhesions on surfaces.

CFD simulation of a novel bileaflet mechanical heart valve prosthesis : an estimation of the Venturi passage formed by the leaflets

The aim of this study was to validate the flow characteristics of the novel Helmholtz-Institute Aachen Bileaflet (HIA-BL) heart valve prosthesis. The curved leaflets of the HIA-BL valve form a Venturi passage between the leaflets at peak systole. By narrowing the cross section the flow accelerates and the static pressure at the central passage decreases according to the Venturi effect. The low-pressure zone between the leaflets is expected to stabilize the leaflets in fully open position at peak systole. To investigate the Venturi passage, the flow fields of two valve geometries were investigated by CFD (Computational Fluid Dynamics): one geometry exhibits curved leaflets resulting in a Venturi passage; the other geometry features straight leaflets. The flow profiles, pressure distribution and resulting torque of both passages were compared and investigated. Although flow profiles downstream of both valves were similar, the flow passages between the leaflets were different for the investigated leaflet geometries. The straight leaflet passage showed a large boundary layer separation zone near the leaflets and the lowest pressure at the leading edge of the leaflet. The Venturi passage showed a reduction of the boundary layer separation zones and the lowest pressure between the leaflets could be found in the narrowest flow cross section of the Venturi passage. Additionally, the resulting torque showed that the Venturi passage produced an opening momentum. The results demonstrate that the Venturi passage stabilizes the leaflets in open position at peak systole.

Aortic Root Compliance Influences Hemolysis in Mechanical Heart Valve Prostheses: An In-Vitro Study:

Mechanical heart valve prostheses are known to activate coagulation and cause hemolysis. Both are particularly dependent on the leaflet dynamics, which in turn depends on the flow field in the aortic root influenced by the aortic root geometry and its compliance. Compliance reduction of large vessels occurs in aging patients, both in those who have atherosclerotic diseases and those who do not. In this study we investigated the correlation between hemolysis and the compliance of the proximal aorta in a novel, pulsatile in vitro blood tester using porcine blood. Two mechanical heart valves, the St Jude Medical (SJM) bileaflet valve and a trileaflet valve prototype (Triflo) were tested for hemolysis under physiological conditions (120/80 mm Hg, 4.5 l/min, 70 bpm) and using two different tester setups: with a stiff aorta and with a compliant aorta. Valve dynamics were subsequently analyzed via high-speed videos. In the tests with the Triflo valve, the free plasma hemoglobin increased by 13.4 mg/dl for the flexible and by 19.3 mg/dl for the stiff setup during the 3-hour test. The FFT spectra and closing speed showed slight differences for both setups. Free plasma hemoglobin for the SJM valve was up by 22.2 mg/dl in the flexible and 42.7 mg/dl in the stiff setup. Cavitation induced by the higher closing speed might be responsible for this, which is also indicated by the sound spectrum elevation above 16 kHz.

Impact of Hyperthermal Rotary Blood Pump Surfaces on Blood Clotting Behavior: An Approach

The influence of heat dissipating systems, such as rotary blood pumps, was investigated. Titanium cylinders as rotary blood pump housing dummies were immersed in porcine blood and constantly tempered at specific temperatures (37-60 degrees C) over a defined period of time. The porcine blood was anticoagulated either by low heparin dosage or citrate. At frequent intervals, samples were taken for blood analysis and the determination of the plasmatic coagulation cascade. Blood parameters do not alter at surface temperatures below 50 degrees C. Hyperthermia-induced hemolysis could be confirmed. The plasmatic coagulation cascade is terminated at surface temperatures exceeding 55 degrees C. The adhesion of blood constituents on surfaces is temperature and time dependent, and structural changes of adhesions and blood itself were detected.

The Impact of Hyperthermal Surfaces on Blood in Vitro - An Approach

The influence of heat dissipating systems, such as blood pumps, was investigated. Titanium cylinders as blood pump housing dummies were immersed in porcine blood and constantly tempered at specific temperatures (37 °C - 60 °C) over a defined period of time. The porcine blood was anticoagulated either by low heparin dosage or citrate. At frequent intervals, samples were taken for blood analysis and the determination of the plasmatic coagulation cascade.