Thrombophilia and direct thrombin inhibitor lepirudin clinical and monitoring aspects

Thrombophilia (TF) predisposes both to venous and arterial thrombosis at a young age. TF may also impact the thrombosis or stenosis of hemodialysis (HD) vascular access in patients with end-stage renal disease (ESRD). When involved in severe thrombosis TF may associate with inappropriate response to anticoagulation. Lepirudin, a potent direct thrombin inhibitor (DTI), indicated for heparin-induced thrombocytopenia-related thrombosis, could offer a treatment alternative in TF. Monitoring of narrow-ranged lepirudin demands new insights also in laboratory. The above issues constitute the targets in this thesis. We evaluated the prevalence of TF in patients with ESRD and its impact upon thrombosis- or stenosis-free survival of the vascular access. Altogether 237 ESRD patients were prospectively screened for TF and thrombogenic risk factors prior to HD access surgery in 2002-2004 (mean follow-up of 3.6 years). TF was evident in 43 (18%) of the ESRD patients, more often in males (23 vs. 9%, p=0.009). Known gene mutations of FV Leiden and FII G20210A occurred in 4%. Vascular access sufficiently matured in 226 (95%). The 1-year thrombosis- and stenosis-free access survival was 72%. Female gender (hazards ratio, HR, 2.5; 95% CI 1.6-3.9) and TF (HR 1.9, 95% CI 1.1-3.3) were independent risk factors for the shortened thrombosis- and stenosis-free survival. Additionally, TF or thrombogenic background was found in relatively young patients having severe thrombosis either in hepatic veins (Budd-Chiari syndrome, BCS, one patient) or inoperable critical limb ischemia (CLI, six patients). Lepirudin was evaluated in an off-label setting in the severe thrombosis after inefficacious traditional anticoagulation without other treatment options except severe invasive procedures, such as lower extremity amputation. Lepirudin treatments were repeatedly monitored clinically and with laboratory assessments (e.g. activated partial thromboplastin time, APTT). Our preliminary studies with lepirudin in thrombotic calamities appeared safe, and no bleeds occurred. An effective DTI lepirudin calmed thrombosis as all patients gradually recovered. Only one limb amputation was performed 3 years later during the follow-up (mean 4 years). Furthermore, we aimed to overcome the limitations of APTT and confounding effects of warfarin (INR of 1.5-3.9) and lupus anticoagulant (LA). Lepirudin responses were assessed in vitro by five specific laboratory methods. Ecarin chromogenic assay (ECA) or anti-Factor IIa (anti-FIIa) correlated precisely (r=0.99) with each other and with spiked lepirudin in all plasma pools: normal, warfarin, and LA-containing plasma. In contrast, in the presence of warfarin and LA both APTT and prothrombinase-induced clotting time (PiCT®) were limited by non-linear and imprecise dose responses. As a global coagulation test APTT is useful in parallel to the precise chromogenic methods ECA or Anti-FIIa in challenging clinical situations. Lepirudin treatment requires multidisciplinary approach to ensure appropriate patient selection, interpretation of laboratory monitoring, and treatment safety. TF seemed to be associated with complicated thrombotic events, in venous (BCS), arterial (CLI), and vascular access systems. TF screening should be aimed to patients with repeated access complications or prior unprovoked thromboembolic events. Lepirudin inhibits free and clot-bound thrombin which heparin fails to inhibit. Lepirudin seems to offer a potent and safe option for treatment of severe thrombosis. Multi-centered randomized trials are necessary to assess the possible management of complicated thrombotic events with DTIs like lepirudin and seek prevention options against access complications.

Long-term Accelerated Multistress Aging of Composite Outdoor Polymeric Insulators

Polymeric outdoor insulators are being increasingly used for electrical power transmission and distribution in the recent years. One of the current topics of interest for the power transmission community is the aging of such outdoor polymeric insulators. A few research groups are carrying out aging studies at room temperature with wet period as an integral part of multistress aging cycle as specified by IEC standards. However, aging effect due to dry conditions alone at elevated temperatures and electric stress in the presence of radiation environment has probably not been explored. It is interesting to study and understand the insulator performance under dry conditions where wet periods are either rare or absent and to estimate the extent of aging caused by multiple stresses. This paper deals with the long-term accelerated multistress aging on full-scale 11 kV distribution class composite silicone rubber insulators. In order to assess the long-term synergistic effect of electric stress, temperature and UV radiation on insulators, they are subjected to accelerated aging in a specially designed multistress-aging chamber for 3800 hours. All the stresses are applied at an accelerated level. Using a data acquisition system developed for the work, leakage current has been monitored in LabVIEW environment. Chemical changes due to degradations have been studied using Energy Dispersive X-Ray analysis, Scanning Electron Microscope and Fourier transform Infrared Spectroscopy. Periodically different parameters like low molecular weight (LMW) molecular content, hydrophobicity, leakage current and surface morphology were monitored. The aging study is under progress and only intermediate results are presented in this paper.

Probing the aging effect in metallic polypyrrole by terahertz time-domain spectroscopy

Terahertz time-domain spectroscopy has been carried out on a metallic film of polypyrrole (PPy doped by PF6). The sample was exposed to air to investigate how the conductivity of the film varies as a function of time. The absorption and dispersion of the film decrease during initial days, and then tend to saturate. The conductivity of unaged sample follows the Drude model, and upon aging the data fit to the localization-modified Drude model. The fitting parameters show that the number of charge carriers decreases during the aging process. The initial rapid decrease in conductivity suggests that some of the delocalized carriers are localized due to aging. (C) 2007 American Institute of Physics.