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Intern Emerg Med ; 13(7): 1051-1058, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29790125


The management of major bleeding in patients treated with direct oral anticoagulants (DOACs) is still not well established. START-Events, a branch of the START registry (Survey on anTicoagulated pAtients RegisTer) (NCT02219984), aims to describe the actual management of bleeding or recurrent thrombotic events in routine clinical practice. We here present the results of the management of bleeding patients. The START-Event registry is a prospective, observational, multicenter, international study. Baseline characteristics (demographic, clinical, risk factors) of patients, laboratory data at admission and during follow-up, site of bleeding, therapeutic strategies, and outcomes at the time of hospital discharge and after 6 months were recorded on a web-based case report form. Between January 2015 and December 2016, 117 patients with major bleeding events were enrolled. Non-valvular atrial fibrillation (NVAF) was the indication for treatment in 84% (62% males); 53 patients had intracranial bleeding (13 fatal), 42 had gastrointestinal bleeding (1 fatal), and 22 had bleeding in other sites. Therapeutic interventions for the management of bleeding were performed in 71% of patients. Therapeutic strategies with/without surgery or invasive procedures included: fluid replacement or red blood cells transfusion, prothrombin complex concentrates (3 or 4 factors), antifibrinolytic drugs, and the administration of idarucizumab. Creatinine, blood cell count, and PT/aPTT were the most frequent tests requested, while specific DOAC measurements were performed in 23% of patients. Mortality during hospitalization was 11.9%, at 6-month follow-up 15.5%. Our data confirm a high heterogeneity in the management of bleeding complications in patients treated with DOACs.

Anticoagulantes/farmacocinética , Hemorragia/mortalidade , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Fatores de Coagulação Sanguínea/análise , Dabigatrana/farmacocinética , Dabigatrana/uso terapêutico , Feminino , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Humanos , Masculino , Estudos Prospectivos , Pirazóis/farmacocinética , Pirazóis/uso terapêutico , Piridonas/farmacocinética , Piridonas/uso terapêutico , Sistema de Registros/estatística & dados numéricos , Rivaroxabana/farmacocinética , Rivaroxabana/uso terapêutico , Resultado do Tratamento , Fibrilação Ventricular/tratamento farmacológico
Blood Coagul Fibrinolysis ; 26(2): 225-9, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25629417


Dabigatran is an oral direct inhibitor indicated for stroke prevention in patients with atrial fibrillation. Unlike warfarin, dabigatran's observed therapeutic window and minimal drug-to-drug interaction suggest that laboratory test and dose adjustments are not necessary; nevertheless, circumstances of excessive anticoagulation, decreased kidney function, and instances of significant bleeding and thrombosis require laboratory assessment. In order to gather experience in the management of global [activated partial thromboplastin time (APTT) and thrombin time (TT) with extended endpoint] and specific [ecarin chromogenic assay (ECA) and diluted thrombin time (dTT)] laboratory coagulation tests in patients receiving dabigatran with untoward effects, we describe a case in which hemodialysis was used in attempt to remove dabigatran in a patient with excessive anticoagulation, rectal bleeding, and severe anemia. Our experience confirmed that APTT is an unreliable method for the assessment of dabigatran in patients with acute complications because it was often normal in spite of the therapeutic drug plasma levels. Both ECA and dTT showed a linear correlation with dabigatran levels over a broad range, and identified therapeutic and supratherapeutic levels. TT assay, which is highly sensitive to dabigatran, correlated well and linearly not only with low drug levels, but also, because of the introduction of the extended endpoint (400 s), with high concentrations of the drug, and demonstrated to be a simple and reliable alternative to ECA and dTT to assess dabigatran in patients with acute complications.

Antitrombinas/envenenamento , Benzimidazóis/envenenamento , Coagulação Sanguínea/efeitos dos fármacos , Overdose de Drogas/terapia , Diálise Renal/métodos , beta-Alanina/análogos & derivados , Idoso de 80 Anos ou mais , Dabigatrana , Overdose de Drogas/sangue , Humanos , Masculino , beta-Alanina/envenenamento
G Ital Nefrol ; 31(2)2014.
Artigo em Italiano | MEDLINE | ID: mdl-24777926


A 85-year-old man, with CKD (e-GFR 35 mL/min), had been given Dabigatran (a direct thrombin inhibitor) at 110 mg daily dose because of atrial fibrillation. Due to intercurrent diarrhea and dehydration, renal function worsened (e-GFR 11 mL/min) and Dabigatran excretion decreased, thereby inducing drug overload. In this case, Dabigatran must be removed by dialysis, but the most appropriate schedule is still undefined. The effects of both continuous haemodiafiltration (CVVHDF) and intermittent haemodialysis (IHD) on plasma Dabigatran (Echarin Chromogenic Assay) were reported. Dialysis clearance of Dabigatran was reported as ratio to urea clearance (Dab/Urea(Cl)). Coagulation was assessed by both DOA-aPTTratio and Thrombin Time-ratio (TTratio). Dabigatran was elevated at 597 ng/mL predialysis (bleeding threshold being 30 ng/mL), and decreased to 96 ng/mL (-84%) after 20 hours of CVVHDF (Urea(Cl) = 67 mL/min). Dab/Urea(Cl) was 0.49. Three hours after dialysis, Dabigatran rebounded to 208 ng/mL. On IHD (Urea(Cl)=238 mL/min), predialysis Dabigatran was 52 ng/mL and decreased to 8 ng/mL (-85%) after 3.5 hours of treatment. Dab/Urea(Cl) was 0.47. Fourteen hours later, Dabigatran rebounded at 19 ng/mL. There was a positive correlation between Dabigatran and TTratio (r = 0.92; p<0.0001), whereas DOA-aPTT did not increase above 2.5 times the reference values, even in face of the highest values of Dabigatran. Therefore, TTratio is more reliable than DOA-aPTT in detecting Dabigatran overdose. Post-dialysis rebound of Dabigatran occurred also with CVVHDF, thereby suggesting that accurate monitoring of both Dabigatran levels and bleeding risk are mandatory, also after long-lasting dialysis sessions.

Antitrombinas/envenenamento , Benzimidazóis/envenenamento , Overdose de Drogas/terapia , Terapia de Substituição Renal , beta-Alanina/análogos & derivados , Idoso de 80 Anos ou mais , Dabigatrana , Humanos , Masculino , Diálise Renal , beta-Alanina/envenenamento
Br J Haematol ; 161(5): 688-94, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23573950


Givinostat, a histone-deacetylase inhibitor (HDACi), inhibits proliferation of cells bearing the JAK2 V617F mutation and has shown significant activity with good tolerability in patients with chronic myeloproliferative neoplasms (MPN). In this multicentre, open-label, phase II study, 44 patients with polycythaemia vera (PV), unresponsive to the maximum tolerated doses (MTD) of hydroxycarbamide (HC), were treated with Givinostat (50 or 100 mg/d) in combination with MTD of HC. The European LeukaemiaNet response criteria were used to assess the primary endpoint after 12 weeks of treatment. Complete or partial response was observed in 55% and 50% of patients receiving 50 or 100 mg of Givinostat, respectively. Control of pruritus was observed in 64% and 67% of patients in the 50 and 100 mg groups, respectively. The combination of Givinostat and HC was well tolerated: eight patients (18%) discontinued, four in each treatment arm; grade 3 adverse events were reported in one patient (4·5%) in each treatment arm. The combined use of Givinostat and HC was safe and clinically effective in HC-unresponsive PV patients.

Carbamatos/uso terapêutico , Inibidores de Histona Desacetilases/uso terapêutico , Hidroxiureia/uso terapêutico , Inibidores da Síntese de Ácido Nucleico/uso terapêutico , Policitemia Vera/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carbamatos/administração & dosagem , Carbamatos/efeitos adversos , Relação Dose-Resposta a Droga , Esquema de Medicação , Quimioterapia Combinada , Feminino , Inibidores de Histona Desacetilases/administração & dosagem , Inibidores de Histona Desacetilases/efeitos adversos , Humanos , Hidroxiureia/administração & dosagem , Hidroxiureia/efeitos adversos , Masculino , Pessoa de Meia-Idade , Inibidores da Síntese de Ácido Nucleico/administração & dosagem , Inibidores da Síntese de Ácido Nucleico/efeitos adversos , Falha de Tratamento , Resultado do Tratamento
Exp Hematol ; 41(7): 627-34, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23542632


The purpose of this study was to investigate telomere length (TL) in Ph-negative chronic myeloproliferative neoplasms (Ph-neg-CMNs), and the possible association of TL with disease progression and hydroxycarbamide (HU) treatment. TL was analyzed in peripheral blood samples from 239 patients with Ph-neg-CMNs, including polycythemia vera (PV), essential thrombocythemia and myelofibrosis (MF), and compared with age-matched healthy control subjects (CTR), along with some cases of secondary erythrocytosis (SE). More than half of the patients with CMN received at least 1 year of cytoreduction, mainly HU, before TL analysis. JAK2 mutation analysis was performed as well. TL was significantly shortened in patients with CMN compared with CTR (p < 0.0001). PV and MF showed the most pronounced decrease (p < 0.0001), whereas both essential thrombocythemia and SE showed no significant difference in TL compared with CTR. A short TL correlated with JAK2-V617F allele burden greater than 50% (p = 0.0025), age (p = 0.0132) and diagnosis of PV (p = 0.0122). No correlation was found with disease duration, history of thrombosis, cytoreductive treatment, antiaggregation agents, adverse cytogenetics, phlebotomies, or time to evolution to MF. In summary, TL is distinctly shortened in PV and MF, and it inversely correlates with JAK2V617F allele burden. In addition, HU is unlikely to contribute to telomere erosion. Lastly, PV and SE significantly differ in TL. Therefore, TL could be an additional diagnostic marker to identify and monitor Ph-neg-CMN patients.

Hidroxiureia/uso terapêutico , Transtornos Mieloproliferativos/genética , Telômero/ultraestrutura , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Criança , Pré-Escolar , Células Clonais/patologia , Feminino , Humanos , Hibridização in Situ Fluorescente , Lactente , Recém-Nascido , Janus Quinase 2/genética , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Transtornos Mieloproliferativos/tratamento farmacológico , Transtornos Mieloproliferativos/patologia , Mutação Puntual , Policitemia/tratamento farmacológico , Policitemia/genética , Policitemia/patologia , Policitemia Vera/tratamento farmacológico , Policitemia Vera/genética , Policitemia Vera/patologia , Mielofibrose Primária/tratamento farmacológico , Mielofibrose Primária/genética , Mielofibrose Primária/patologia , Adulto Jovem
Blood Coagul Fibrinolysis ; 23(4): 331-4, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22343685


This case report describes a patient with relapsed primary immune thrombocytopenic purpura (ITP), in which splenectomy was not possible due to the persistence of a low platelet count despite treatment with corticosteroids, intravenous immunoglobulins (IVIG) and platelet transfusion treatment. As an attempt to increase platelet count prior to performing splenectomy, the thrombopoietin receptor agonist, romiplostim, was administered in combination with steroids and IVIG. A single administration of romiplostim was found to be markedly effective, allowing a rapid and notable platelet increase, required for a well tolerated splenectomy. This case confirms the potent activity of romiplostim in ITP, and indicates that patients with recurrent primary ITP who are unresponsive to conventional immunosuppressive therapy may benefit from the addition of a short course of romiplostim.

Plaquetas/efeitos dos fármacos , Imunoglobulinas/uso terapêutico , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Receptores Fc/uso terapêutico , Receptores de Trombopoetina/agonistas , Proteínas Recombinantes de Fusão/uso terapêutico , Esteroides/uso terapêutico , Trombopoetina/uso terapêutico , Adulto , Feminino , Humanos , Contagem de Plaquetas , Púrpura Trombocitopênica Idiopática/sangue , Púrpura Trombocitopênica Idiopática/cirurgia , Esplenectomia/métodos