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“The Regulation of Coagulation in Major Orthopedic surgery reducing the Risk of DVT and PE (RECORD) clinical program of rivaroxaban consists of 4 phase III clinical trials comparing rivaroxaban with enoxaparin for the prevention of venous thromboembolism (VTE) in patients undergoing either total hip or total knee replacement surgery. Despite the comprehensive and extensive nature of this program, it had some logistic issues that included the dosing of the enoxaparin which was not only inconsistent

with the recommendations but the dosages used were not optimal. The duration of treatment while consistent with rivaroxaban did vary with enoxaparin and was somewhat short. The bleeding definitions and safety evaluations were not consistent in accordance with the Current recommendations. Moreover, the RECORD program has check details no power to show differences in major bleeding. The cardiovascular rebound phenomenon should have been adequately

addressed and may require additional clinical validation to establish the safety of rivaroxaban. Although the US Food and Drug Administration (FDA) advisory committee has recommended approval of rivaroxaban, the reported analysis strongly suggests additional clinical validation on the claimed benefit/risk ratio of this monotherapeutic anticoagulant.”
“Recently, a contaminant buy ML323 was found in some clinically used Unfractionated heparin (UFH) preparations. Administration of this UFH was associated MK2206 with an increased risk of developing a wide range

of adverse effects including death. To further investigate the chemical profile of the contaminant, contaminated batches of UFH were treated by exhaustive nitrous acid depolymerization followed by methanol precipitation to remove heparin oligosaccharides. Because contaminated heparins may have been used as starting material in the production of low-molecular-weight hepatitis (LMWHs), a similar procedure was carried Out using an experimental batch of enoxaparin prepared from contaminated heparin. While high-pressure liquid chromatography (HPLC) analysis of contaminated heparin did not distinguish the presence of the contaminant, it Could readily be observed as a high-molecular weight Shoulder in the elution Profile of contaminated enoxaparin. Digesting contaminated heparin with heparinase-I prior to HPLC analysis showed the presence of a nondigestible component (15%-30% of the mixture). This contaminant was also resistant to degradation by chondroitinases A, B, and C. Proton nuclear magnetic resonance (NMR) indicated that the contaminant was oversulfated chondroitin sulfate (OSCS). Size-exclusion chromatography indicated that the mean molecular weight of the OSCS was 16.8 kD, comparable to that of a synthetic porcine cartilage OSCS preparation that Was used as a reference material (17.2 kD).