Summary
Objective
To evaluate the effectiveness and safety of prothrombin complex concentrates (PCCs) in approved and off‐label indications.
Background
PCCs are approved for the urgent reversal of ...vitamin K antagonists (VKAs). Data concerning the efficacy, safety and dosing for off‐label indications are limited, but they are included in massive bleeding protocols.
Methods
This was a retrospective review of cases treated with four‐factor PCCs (4F‐PCCs) between January 2009 and 2016. Efficacy end‐points include: (i) VKA reversal efficacy assessed by international normalised ratio (INR) normalisation (<1·5) and (ii) clinical efficacy as bleeding cessation and/or decreased number of transfused blood components and 24‐h mortality in bleeding coagulopathy. The safety end‐point is the incidence of thromboembolic events.
Results
A total of 328 patients were included (51·8% male, median age 78 years old). Indications were as follows: VKA reversal (66·6%), bleeding coagulopathy (30·5%) and direct anticoagulant (DOAC) reversal due to bleeding (2·5%).
VKA reversal was effective in 97·1% of patients, and 76·5% demonstrated complete reversal (INR < 1·5); only 34·3% patients needed hemoderivatives. Prior to emergency procedures, PCCs achieved global responses in 83% of patients, with no bleeding complication during intervention. DOAC reversal was effective in 88·9% of patients. Bleeding cessation was associated with the dose administered (P = 0·002). In coagulopathy bleeding, haemorrhage cessation, established by the International Society of Thrombosis and Haemostais (ISTH) definition, occurred in 56·7% of massive bleeding events and in 42·5% of other coagulopathies; 24‐h mortality was 30%, mainly related to active bleeding. Ten thrombotic episodes were observed (3·1%).
Conclusion
4F‐PCC was effective as adjuvant treatment with an acceptable safety profile, not only for the emergent reversal of VKAs but also for refractory coagulopathy associated with major bleeding.
Patients with cancer present with an elevated risk of thrombosis, which entails high morbidity and mortality. Various predictive scales that incorporate clinical and biological data have been ...developed to identify those at high risk of thrombosis, but, in general, they do not allow for the optimal selection of subjects who are candidates for thromboprophylaxis. Recent studies have demonstrated that the mutation profile has a high impact on the risk of thrombosis; this will facilitate developing new predictive models of thrombosis in patients with cancer.
Los pacientes con cáncer presentan un riesgo elevado de trombosis, que condiciona una elevada morbimortalidad. Se han desarrollado diversas escalas predictivas para la identificación de aquellos con alto riesgo trombótico, incorporando datos clínicos y biológicos, pero, en general, no permiten una selección óptima de los sujetos candidatos para recibir tromboprofilaxis. Estudios recientes demuestran que el perfil mutacional tiene un alto impacto sobre el riesgo trombótico, lo que va a facilitar el desarrollo de nuevos modelos predictivos de trombosis en pacientes con cáncer.
The publisher regrets that this article has been temporarily removed. A replacement will appear as soon as possible in which the reason for the removal of the article will be specified, or the ...article will be reinstated. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.
The publisher regrets that this article has been temporarily removed. A replacement will appear as soon as possible in which the reason for the removal of the article will be specified, or the ...article will be reinstated. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.
Obinutuzumab in follicular lymphoma Martinez-Calle, N; Figueroa-Mora, R; Villar-Fernandez, S ...
Drugs of today (Barcelona, Spain : 1998),
12/2016, Letnik:
52, Številka:
12
Journal Article
The CD20 marker continues to be exploited as a therapeutic target for non-Hodgkin's lymphoma. Obinutuzumab is part of a new generation of anti-CD20 monoclonal antibodies, which are synthesized using ...molecular engineering technology, resulting in novel target epitopes and unprecedented optimization of antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis. Rituximab is the current gold standard for anti-CD20 therapy, yet despite outstanding results published over the past decade, many patients continue to relapse after anti-CD20 regimens. Obinutuzumab is slowly positioning itself in the treatment of CD20+ B-cell neoplasms. On the basis of favorable results from the phase III GADOLIN trial, obinutuzumab was recently approved by the U.S. Food and Drug Administration in combination with bendamustine followed by obinutuzumab maintenance, for the treatment of follicular lymphoma (FL) patients who relapsed or are refractory to a rituximab-containing regimen. Additional phase III trials are underway to test obinutuzumab as a first-line anti-CD20 agent in FL with good preliminary results (GALLIUM trial); thus, it is likely that obinutuzumab will soon achieve a first-line indication. It is plausible that obinutuzumab will replace rituximab as the gold standard for chemoimmunotherapy in FL, although some safety concerns still need to be resolved. This review will address the preclinical pharmacology and the main aspects of the clinical development of obinutuzumab for the treatment of FL.
PDF