Hemorrhagic Complications of Anticoagulant Treatment

Levine, Mark; Raskob, Gary E.; Landefeld, Seth; Kearon, Clive

doi:10.1378/chest.119.1_suppl.108s

Cited by 682 publications

(152 citation statements)

References 149 publications

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“…They are characterised by a narrow therapeutic range and despite regular anticoagulant effect monitoring bleeding complications frequently occur. These are mainly attributed to pharmacokinetic variations due to genetic aspects or drug-drug interactions [1][2][3]. Previous methods for the determination of oral anticoagulants in biological fluids were mostly restricted to the quantification of the parent compounds [4][5][6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Determination of phenprocoumon, warfarin and their monohydroxylated metabolites in human plasma and urine by liquid chromatography–mass spectrometry after solid-phase extraction

Ufer

Kammerer

Kirchheiner

et al. 2004

Journal of Chromatography B

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Section: Introductionmentioning

confidence: 99%

Determination of phenprocoumon, warfarin and their monohydroxylated metabolites in human plasma and urine by liquid chromatography–mass spectrometry after solid-phase extraction

Ufer

Kammerer

Kirchheiner

et al. 2004

Journal of Chromatography B

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“…Anticoagulant therapies are in great demand to block undesired thrombosis of surgery patients and to treat many lifethreatening diseases such as stroke, acute coronary syndrome, and deep vein/pulmonary embolism (35). Current therapies with heparin or coumarins have limited efficacy and safety records (36,37), prompting synthesis of many small molecules intended to inhibit specific target proteases, such as thrombin, factor VIIa (fVIIa), factor IXa (fIXa), and factor Xa (fXa), within the coagulation pathways (34). However, because of the similarity among plasma kallikrein and the coagulation factors, including a preference for arginine at the S1 substrate-binding site, many inhibitors designed for other coagulation factors also inhibit plasma kallikrein.…”

mentioning

confidence: 99%

Expression, Crystallization, and Three-dimensional Structure of the Catalytic Domain of Human Plasma Kallikrein

Tang¹,

Yu²,

Williams³

et al. 2005

Journal of Biological Chemistry

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Plasma kallikrein is a serine protease that has many important functions, including modulation of blood pressure, complement activation, and mediation and maintenance of inflammatory responses. Although plasma kallikrein has been purified for 40 years, its structure has not been elucidated. In this report, we described two systems (Pichia pastoris and baculovirus/Sf9 cells) for expression of the protease domain of plasma kallikrein, along with the purification and high resolution crystal structures of the two recombinant forms. In the Pichia pastoris system, the protease domain was expressed as a heterogeneously glycosylated zymogen that was activated by limited trypsin digestion and treated with endoglycosidase H deglycosidase to reduce heterogeneity from the glycosylation. The resulting protein was chromatographically resolved into four components, one of which was crystallized. In the baculovirus/Sf9 system, homogeneous, crystallizable, and nonglycosylated protein was expressed after mutagenizing three asparagines (the glycosylation sites) to glutamates. When assayed against the peptide substrates, pefachrome-PK and oxidized insulin B chain, both forms of the protease domain were found to have catalytic activity similar to that of the full-length protein. Crystallization and x-ray crystal structure determination of both forms have yielded the first three-dimensional views of the catalytic domain of plasma kallikrein. The structures, determined at 1.85 Å for the endoglycosidase H-deglycosylated protease domain produced from P. pastoris and at 1.40 Å for the mutagenically deglycosylated form produced from Sf9 cells, show that the protease domain adopts a typical chymotrypsin-like serine protease conformation. The structural information provides insights into the biochemical and enzymatic properties of plasma kallikrein and paves the way for structure-based design of protease inhibitors that are selective either for or against plasma kallikrein.

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“…Anticoagulation is associated with an increased risk of bleeding [10]. Patients' 1-year bleeding risks can be assessed using the HAS-BLED score [hypertension, abnormal renal and liver function, stroke, bleeding history or predisposition, labile INR (international normalized ratio), elderly, drugs, or alcohol concomitantly); risk stratification using this tool is recommended by European but not US guidelines [11,12,13].…”

Section: Overall Bleeding Riskmentioning

confidence: 99%

Practical Considerations for the Nonvitamin K Antagonist Oral Anticoagulants

Trikha

Kowey

2016

Cardiology

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Objectives: Dabigatran, rivaroxaban, apixaban, and edoxaban are nonvitamin K antagonist oral anticoagulants (NOACs) approved for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF). Phase-3 clinical trials demonstrated NOACs were as effective as warfarin in the prevention of stroke or systemic embolism and associated with decreased incidences of intracranial bleeding. Additionally, NOACs provide quicker onset of action, simpler dosing, more predictable pharmacokinetic profiles, and decreased food and drug interactions compared with warfarin. Despite the advantages of NOACs, the lack of knowledge may limit their use in clinical practice. Methods: A search was performed on the terms ‘atrial fibrillation' and ‘dabigatran', ‘apixaban', ‘edoxaban', or ‘rivaroxaban' to identify relevant papers; large randomized clinical trials, meta-analyses, and treatment guideline recommendations were given preference. Searches to identify registries, treatment guidelines, and meta-analyses relevant to patient subgroups were also employed. Results: Dosing recommendations, initiation of treatment, and applications in patients who undergo NVAF procedures, have mechanical heart valves, or experience other cardiovascular conditions such as myocardial infarction, previous stroke, and valvular heart disease are summarized. The NOAC-specific reversal approaches are also discussed. Conclusions: Several important factors should be considered regarding the adequate use of NOACs, especially in patients with renal impairment or cardiovascular conditions other than NVAF.

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Hemorrhagic Complications of Anticoagulant Treatment

Cited by 682 publications

References 149 publications

Determination of phenprocoumon, warfarin and their monohydroxylated metabolites in human plasma and urine by liquid chromatography–mass spectrometry after solid-phase extraction

Determination of phenprocoumon, warfarin and their monohydroxylated metabolites in human plasma and urine by liquid chromatography–mass spectrometry after solid-phase extraction

Expression, Crystallization, and Three-dimensional Structure of the Catalytic Domain of Human Plasma Kallikrein

Practical Considerations for the Nonvitamin K Antagonist Oral Anticoagulants

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