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1.
Hematology ; 27(1): 318-321, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35231200

RESUMO

BACKGROUND: Heparin-induced thrombocytopenia (HIT) is an immune-mediated adverse drug reaction associated with thrombosis. Clinical scoring systems and the presence of anti-platelet factor 4 (anti-PF4)/heparin antibodies determine the diagnosis. CASE PRESENTATION: A 57-year-old man who was treated with acenocoumarol due to a chronic left ventricular thrombus was admitted to the hospital for severe SARS-CoV-2 pneumonia and pulmonary embolism. The patient was started on bemiparin and discharged. Left lower limb acute arterial ischemia and thrombocytopenia were diagnosed 18 days later. Computed tomography angiography revealed a large left ventricular thrombus and multiple arterial thrombi. Left femoral-popliteal thromboembolectomy was performed. Anti-PF4/heparin antibodies confirmed an HIT diagnosis. Fondaparinux (7.5 mg/24 h) was initiated, but cardiac surgery was necessary. Bivalirudin was used during surgery, with an initial load (1.25 mg/kg) and maintenance infusion (2.5 mg/kg/h). The cardiac thrombus was extracted, but the patient experienced a postsurgical myocardial infarction. Percutaneous cardiovascular intervention (PCI) required a bivalirudin load (0.75 mg/kg) and maintenance infusion (1.75 mg/kg/h). No coronary lesions were detected, and argatroban was started afterwards (0.5 µg/kg/min). When the platelet count exceeded 100 × 109/L, acenocoumarol was initiated. Thereupon, acetylsalicylic acid (100 mg/24 h) was added. No other complications have been reported to date. CONCLUSION: The clinical presentation of intraventricular and multiple arterial thrombi is remarkable. SARS-CoV-2 infection likely contributed to a hypercoagulable state. The management of patients with HIT undergoing cardiac surgery is challenging. If surgery cannot be delayed, then treatment with bivalirudin is recommended. Additionally, this drug is recommended for PCI. Bivalirudin is safe and well-tolerated in both procedures.


Assuntos
Acenocumarol/administração & dosagem , Anticoagulantes/administração & dosagem , Arginina/análogos & derivados , COVID-19/tratamento farmacológico , Heparina , Hirudinas/administração & dosagem , Fragmentos de Peptídeos/administração & dosagem , Intervenção Coronária Percutânea , Ácidos Pipecólicos/administração & dosagem , SARS-CoV-2 , Sulfonamidas/administração & dosagem , Trombocitopenia , Trombose , Arginina/administração & dosagem , COVID-19/complicações , Heparina/administração & dosagem , Heparina/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/administração & dosagem , Trombocitopenia/induzido quimicamente , Trombocitopenia/terapia , Trombose/induzido quimicamente , Trombose/terapia
2.
Crit Rev Anal Chem ; 52(3): 627-636, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-32897755

RESUMO

Acenocoumarol is an oral anticoagulant medicinal agent is frequently prescribed for the prophylaxis and the management of thromboembolic events. Acenocoumarol is prescribed in the form of racemic mixture and S- form is a more influential isomer. Acenocoumarol starts quickly with action and absorption, and the effect lasts for 15-20 h. In most patients, the therapeutic prothrombin range is caused 36 h after the primary dose. This review offers a detailed overview of the various analytical methodologies published in the literature from 1976 to uptil now for evaluation acenocoumarol and its combinations in specimens. The present review also stated the chiral analytical methods for the quantification of its enantiomers. A detailed study of the work revealed several analytical methodologies are routinely used for estimation of acenocoumarol includes UV/Vis-Spectrophotometry, liquid chromatography-mass spectrophotometry, high-performance liquid-chromatography, gas chromatography, high-performance thin-layer chromatography, capillary electrophoresis, Fourier-transform infrared spectroscopy and many miscellaneous techniques. Pharmaceutical analysis carried out the prominent task to understand the knowledge of the physicochemical properties of the medicinal agent; since the establishment of a new analytical method is still a challenging task for a research scientist. Thus, the present review will help to research scientist for the development of new analytical methods for the acenocoumarol.


Assuntos
Acenocumarol , Eletroforese Capilar , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia em Camada Delgada , Humanos , Preparações Farmacêuticas
3.
FEMS Microbiol Lett ; 368(18)2021 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-34529059

RESUMO

The increased interest of consumers in probiotic foods requires a deeper knowledge on the possible interactions with drugs, because their pharmacological properties could be modified. In this context, these studies are relevant for drugs such as acenocoumarol, whose dosage must be controlled due to, among other factors, food-drug interactions. Acenocoumarol is an oral anticoagulant with a narrow therapeutic range. The aim of the present research is to evaluate, in vitro, the effect of bifidobacteria on acenocoumarol. The drug was incubated with Bifidobacterium bifidum CIDCA 5310 or Bifidobacterium adolescentis CIDCA 5317 in MRS broth at 37°C for 24 h in anaerobic conditions. The effect of incubation with sterilized spent culture supernatants (SSCS) was also evaluated. Analysis by RP-HPLC showed that both bifidobacterial strains reduced the area of the acenocoumarol peak and two new peaks were evidenced. In addition, a decrease in the intensity of the bands at 1650, 1390 and 1110/cm was observed in the FTIR spectroscopic determinations. Moreover, a new band appeared at 1720/cm. No effect on the drug was observed when incubation was performed with SSCS. The present study showed a significant change in the concentration of the anticoagulant after incubation with bifidobacteria and results are compatible with biomodification of the drug due to enzymatic activity of bifidobacteria.


Assuntos
Acenocumarol , Bifidobacterium , Acenocumarol/metabolismo , Anticoagulantes/metabolismo , Bifidobacterium/metabolismo , Interações Medicamentosas , Probióticos/metabolismo
4.
Ned Tijdschr Geneeskd ; 1652021 09 09.
Artigo em Holandês | MEDLINE | ID: mdl-34523845

RESUMO

Acenocoumarol and phenprocoumon are vitamin K antagonists (VKA) with average half-lives of 11 hours and 160 hours, respectively. They are used to treat and prevent thrombosis in mechanical cardiac valve replacement, atrial fibrillation and venous thromboembolism. There are historical regional differences in preferred VKA in the Netherlands. Safe and effective treatment requires the international normalized ratios (INRs) to be in the therapeutic range, and stable. Theoretically, the longer-acting phenprocoumon would yield a higher time in therapeutic range (TTR) and lower INR variability. In practice, switching from acenocoumarol to phenprocoumon eventually improves INR variability and in some patients TTR as well. However, during the preceding transition period, INRs are more often volatile and supratherapeutic. Furthermore, switching to an alternative VKA could weaken integrated care, as other healthcare providers are less experienced with it. Healthcare providers must coordinate an intended switch with the anticoagulation clinic.


Assuntos
Acenocumarol , Femprocumona , Acenocumarol/uso terapêutico , Anticoagulantes , Coagulação Sanguínea , Humanos , Coeficiente Internacional Normatizado , Femprocumona/farmacologia
5.
Biomédica (Bogotá) ; 41(3): 403-408, jul.-set. 2021. tab, graf
Artigo em Espanhol | LILACS | ID: biblio-1345391

RESUMO

Se presenta el caso clínico de una paciente de 10 años diagnosticada con miocardiopatía dilatada, quien registró valores en el índice internacional normalizado (International Normalized Ratio, INR) superiores a 10 con la dosis estándar de acenocumarol, además de otros valores que indicaban el estado incoagulable, lo que obligó a suspender y reiniciar el tratamiento en varias ocasiones. Después de más de 30 días de tratamiento, sorprendentemente se lograron los niveles esperados y estables en el INR con la mitad de la dosis recomendada para una paciente de su edad y peso.Se decidió hacer un análisis farmacogenético retrospectivo del caso mediante RT-PCR con sondas TaqMan™ que incluyó cinco polimorfismos de un solo nucleótido y distinto grado de asociación con la dosis-respuesta a los fármacos antivitamínicos K (AVK): rs2108622 (gen CYP4F2), rs9923231, rs7294 (gen VKORC1), rs1799853 y rs1057910 (gen CYP2C9). La paciente resultó ser homocigota para el rs9923231 (VKORC1) y heterocigota para el rs2108622 (CYP4F2). Se ha evidenciado a nivel nacional e internacional que este perfil genético está fuertemente asociado con una necesidad de dosis menores de antivitamínicos K.En conclusión, el análisis farmacogenético confirmó que la condición genética de la paciente, la cual conlleva una baja expresión de la enzima VKORC1 (blanco terapéutico de los antivitamínicos K), hacía predecible la necesidad de una dosis menor a la establecida según los protocolos clínicos recomendados por la Food and Drug Administration (FDA) y PharmGKB™ para los fármacos cumarínicos. El análisis genotípico previo de la paciente hubiese permitido alcanzar el rango terapéutico más prontamente, evitando potenciales riesgos de hemorragia, lo que demuestra la importancia de los análisis farmacogenéticos en tratamientos de gran variabilidad y estrecho rango terapéutico.


Abstract We present the clinical case of a 10-year-old patient diagnosed with dilated cardiomyopathy who registered INR values above 10 upon receiving standard doses of acenocoumarol, as well as other values reported as uncoagulable, forcing the discontinuation and restart of treatment more than once. Expected and stable INR levels were achieved after more than 30 days of treatment, surprisingly with half the recommended dose for a patient of her age and weight. We decided to conduct a retrospective pharmacogenomic analysis including nucleotide genetic polymorphisms (SNPs) with different degrees of association with the dose/response to antivitamin K (AVK) drugs: rs2108622 (gene CYP4F2), rs9923231, rs7294 (gene VKORC1), rs1799853, and rs1057910 (CYP2C9 gene) using TaqMan® RT-PCR. The patient was homozygous for rs9923231 (VKORC1) and heterozygous for rs2108622 (CYP4F2), a genetic profile strongly associated with a requirement of lower AVK doses as shown by national and international evidence. In conclusion, the pharmacogenetic analysis confirmed that this patient's genetic conditions, involving low expression of the VKA therapeutic target, required a lower dose than that established in clinical protocols as recommended by the Food and Drug Administration (FDA) and the PharmGKB® for coumarin drugs. A previous genotypic analysis of the patient would have allowed reaching the therapeutic range sooner, thus avoiding potential bleeding risks. This shows the importance of pharmacogenetic analyses for highly variable treatments with a narrow therapeutic range.


Assuntos
Farmacogenética , Acenocumarol , Vitamina K , Anticoagulantes
7.
Ann Rheum Dis ; 80(5): 598-604, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-34412027

RESUMO

OBJECTIVES: Vitamin K is hypothesised to play a role in osteoarthritis (OA) pathogenesis through effects on vitamin K-dependent bone and cartilage proteins, and therefore may represent a modifiable risk factor. A genetic variant in a vitamin K-dependent protein that is an essential inhibitor for cartilage calcification, matrix Gla protein (MGP), was associated with an increased risk for OA. Vitamin K antagonist anticoagulants (VKAs), such as warfarin and acenocoumarol, act as anticoagulants through inhibition of vitamin K-dependent blood coagulation proteins. VKAs likely also affect the functioning of other vitamin K-dependent proteins such as MGP. METHODS: We investigated the effect of acenocoumarol usage on progression and incidence of radiographic OA in 3494 participants of the Rotterdam Study cohort. We also examined the effect of MGP and VKORC1 single nucleotide variants on this association. RESULTS: Acenocoumarol usage was associated with an increased risk of OA incidence and progression (OR=2.50, 95% CI=1.94-3.20), both for knee (OR=2.34, 95% CI=1.67-3.22) and hip OA (OR=2.74, 95% CI=1.82-4.11). Among acenocoumarol users, carriers of the high VKORC1(BB) expression haplotype together with the MGP OA risk allele (rs1800801-T) had an increased risk of OA incidence and progression (OR=4.18, 95% CI=2.69-6.50), while this relationship was not present in non-users of that group (OR=1.01, 95% CI=0.78-1.33). CONCLUSIONS: These findings support the importance of vitamin K and vitamin K-dependent proteins, as MGP, in the pathogenesis of OA. Additionally, these results may have direct implications for the clinical prevention of OA, supporting the consideration of direct oral anticoagulants in favour of VKAs.


Assuntos
4-Hidroxicumarinas/efeitos adversos , Acenocumarol/efeitos adversos , Anticoagulantes/efeitos adversos , Indenos/efeitos adversos , Osteoartrite/epidemiologia , Vitamina K/antagonistas & inibidores , Idoso , Alelos , Proteínas de Ligação ao Cálcio/efeitos dos fármacos , Progressão da Doença , Proteínas da Matriz Extracelular/efeitos dos fármacos , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Osteoartrite/induzido quimicamente , Osteoartrite/patologia , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos , Vitamina K/efeitos adversos , Vitamina K Epóxido Redutases/efeitos dos fármacos
8.
Pan Afr Med J ; 38: 324, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34285747

RESUMO

Vitamin K antagonists (VKA) based oral anticoagulation, is widely used for the prevention and treatment of thromboembolic disease. The major complication of this therapy is bleeding, and sometimes it can occur in unsuspected areas. Spontaneous pectoral hematoma is one of the rare complications due to over anticoagulation by VKA therapy, with only a few cases reported in the literature. Concomitant use of this therapy with commonly used antibiotic, especially in the elderly with multiple comorbidities, can increase the risk of bleeding. Herein, we report a case of a 72-year-old woman under VKA for the treatment of atrial fibrillation, who presented with a spontaneous massive pectoral hematoma, while using antibiotic to treat a respiratory tract infection, who was successfully managed.


Assuntos
Anticoagulantes/efeitos adversos , Hematoma/induzido quimicamente , Hemorragia/induzido quimicamente , Acenocumarol/administração & dosagem , Acenocumarol/efeitos adversos , Idoso , Anticoagulantes/administração & dosagem , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Feminino , Humanos , Tromboembolia/etiologia , Tromboembolia/prevenção & controle , Vitamina K/antagonistas & inibidores
9.
Eur Rev Med Pharmacol Sci ; 25(13): 4499-4505, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34286492

RESUMO

OBJECTIVE: The embolization of thrombi formed within the atria can occur in any form of atrial fibrillation (AF), i.e., paroxysmal, persistent, or permanent. Although ischemic stroke is the most frequent embolic event associated with AF, embolization to other sites in the pulmonary and systemic circulations may occasionally occur. To avert the risk of embolization, long-term oral anticoagulation therapy is recommended for all AF patients if the CHA2DS2-VASC score is at least 1 for men and at least 2 for women. Since anticoagulant therapy is associated with an increased risk of bleeding, the choice of oral anticoagulant agent should be made by careful consideration of the benefit-to-risk ratio. The use of a newer class of direct oral anticoagulants (DOACs) as an alternative to the anti-vitamin K (AVK) anticoagulants (warfarin, acenocumarol, etc.) can help mitigate the need for periodic monitoring of International Normalized Ratio (INR) and adverse bleeding events that are commonly associated with the use of AVK anticoagulants. Though the use of DOACs (dabigatran, rivaroxaban, edoxaban, apixaban, etc.) is gaining ground due to their relative safety profile and the low overall cost, quite a few clinicians remain skeptical about their use. PATIENTS AND METHODS: Our objective was to evaluate the risk of thromboembolism, stroke, neuropsychiatric illness, depression, and dementia, in patients with non-valvular atrial fibrillation who have been treated with either acenocumarol or apixaban, as well as to see the inflammatory status (ESR) and levels of fibrinogen. Our team at Municipal Emergency University Hospital, Timisoara, Romania, conducted a retrospective study using the medical records of AF patients who were treated with either apixaban or acenocumarol between 2016-2019. We divided the patients into two groups and compared the groups for the aforementioned outcomes. RESULTS: AF patients who were prescribed apixaban had a lower rate of stroke and psychiatric illness compared to those on acenocumarol. No significant correlation was found in terms of risk of developing depression or dementia between the groups. CONCLUSIONS: Non-valvular AF patients on apixaban had lower rates of thromboembolic events than the patients on acenocumarol. This article will serve as a reminder of the positive health and financial outcomes of apixaban use, especially to those healthcare systems that are still oblivious to the decrease in economic burden and gain in quality-adjusted life years (QALY) by the long-term use of NOACS/ DOACS instead of the AVK anticoagulants.


Assuntos
Anticoagulantes/administração & dosagem , Fibrilação Atrial/tratamento farmacológico , Hemorragia/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Acenocumarol/administração & dosagem , Acenocumarol/efeitos adversos , Administração Oral , Idoso , Anticoagulantes/efeitos adversos , Fibrilação Atrial/sangue , Fibrilação Atrial/complicações , Tomada de Decisão Clínica , Feminino , Hemorragia/sangue , Hemorragia/induzido quimicamente , Hemorragia/prevenção & controle , Humanos , Incidência , Coeficiente Internacional Normatizado , Masculino , Pessoa de Meia-Idade , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , Piridonas/administração & dosagem , Piridonas/efeitos adversos , Anos de Vida Ajustados por Qualidade de Vida , Estudos Retrospectivos , Medição de Risco/estatística & dados numéricos , Romênia/epidemiologia , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle
10.
Artigo em Inglês | MEDLINE | ID: mdl-34073370

RESUMO

Introduction: The use of vitamin K antagonists (VKAs) in non-valvular atrial fibrillation (NVAF) is complicated due to the narrow therapeutic margin they present and their unpredictable dose-response relationship. Most studies are based on warfarin, with the results being extrapolated to acenocoumarol. However, studies comparing the two treatments in terms of the degree of anticoagulation control are scarce, justifying the present study. Main factors associated with poor control of time in therapeutic range (TTR) of anticoagulated patients are also studied. Methods: Cross-sectional study, with real-world data from patients treated in primary care (PC). Data were obtained from the System for the Improvement of Research in PC (SIDIAP) database, covering 60,978 NVAF-anticoagulated patients from 287 PC centres in 2018. Descriptive statistics were derived, and odds ratios were estimated by multivariate logistic regression. Results: 41,430 patients were considered: 93% were being treated with acenocoumarol and 7% with warfarin. There was no difference in poor control of TTR between the two types of VKA treatment, acenocoumarol and warfarin (38.9 vs. 38.4; p = 0.610). Poor anticoagulation control was mainly associated with advanced alcoholism (OR = 1.38), liver failure (OR = 1.37) and intracranial haemorrhage (OR = 1.35) as well as female sex, age < 60 years, cardiovascular history, diabetes mellitus and other variables. Conclusions: There is no association between poor anticoagulation control and the type of VKA treatment administered. Factors associated with poor control of TTR must be considered in clinical practice to improve control and decision-making.


Assuntos
Fibrilação Atrial , Acidente Vascular Cerebral , Acenocumarol/uso terapêutico , Anticoagulantes/uso terapêutico , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Atenção Primária à Saúde , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/prevenção & controle , Varfarina/uso terapêutico
11.
JBJS Case Connect ; 11(2)2021 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-34166270

RESUMO

CASE: An elderly, polytrauma patient receiving vitamin K antagonist (VKA) for atrial fibrillation required immediate surgery for open distal tibial fracture. As the initial reversal with vitamin K and fresh frozen plasma by the trauma team was ineffective, the "Bleeding Team" was convened and administrated the appropriate four-factor prothrombin complex regimen, reversing the VKA in a timely manner. Surgery was performed under peripheral nerve blockade subsequently. The postoperative course of the patient was uneventful. CONCLUSION: The individualized approach and the multidisciplinary experts' team guidance is of outmost importance in patients who are treated with anticoagulants and present for nonelective surgery.


Assuntos
Acenocumarol , Fraturas Expostas , Acenocumarol/efeitos adversos , Idoso , Anticoagulantes/efeitos adversos , Fraturas Expostas/complicações , Hemorragia/etiologia , Humanos , Vitamina K
12.
J Gastroenterol Hepatol ; 36(10): 2794-2802, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33978991

RESUMO

BACKGROUND AND AIM: Atrial fibrillation is a major cause of death and disability due to stroke. Vitamin K antagonist drugs are effective for prevention, but they have a narrow therapeutic range and multiple pharmacological interactions. In recent years, new therapeutic alternatives have been searched to minimize complications. The main objective is to evaluate the risk of gastrointestinal bleeding in anticoagulated patients and compare the classic treatment with new anticoagulants. METHODS: We conducted a retrospective cohort study to determine the risk of gastrointestinal bleeding in patients treated with acenocoumarol/dabigatran/rivaroxaban, between 2012 and 2016. We compared the classic with the new anticoagulant group, and a multivariate logistic regression analysis was used to determinate the risk factors of gastrointestinal bleeding. RESULTS: A total of 1213 patients were selected, 52.7% male patients, a mean age of 72.6 years old (± 14.563). 73.6% had atrial fibrilation. 14.5% of patients used acetylsalicylic acid, and 4% clopidogrel. 67.2% had a high-risk CHADS-2 Score, and 36.9% a high-risk HAS-BLED Score. We determined a 5.6% (68) of gastrointestinal bleeding, without differences according to anticoagulant used. The multivariate model showed a greater risk for digestive hemorrhage in patients with a previous hemorrhagic event (odds ratio [OR] = 2.422 95% confidence interval [CI]: 1.101-5.327) and the concomitant therapy with clopidogrel (OR = 2.373 95% CI: 0.996-5.652). CONCLUSIONS: No differences were found in the risk of gastrointestinal bleeding between the different anticoagulants. A previous gastrointestinal bleeding were considered independent risk factor. The HAS-BLED score should be taken into account to make clinical decisions about to prescribe anticoagulant treatment.


Assuntos
Fibrilação Atrial , Dabigatrana , Acenocumarol/efeitos adversos , Administração Oral , Idoso , Anticoagulantes/efeitos adversos , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Clopidogrel , Dabigatrana/efeitos adversos , Feminino , Hemorragia Gastrointestinal/induzido quimicamente , Hemorragia Gastrointestinal/tratamento farmacológico , Hemorragia Gastrointestinal/epidemiologia , Humanos , Masculino , Estudos Retrospectivos , Rivaroxabana/efeitos adversos , Varfarina/uso terapêutico
13.
Pan Afr Med J ; 38: 207, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33995813

RESUMO

Myocardial infarction is a life-threatening emergency with a high mortality rate. A high plasma level of factor VIII is an established risk for both arterial and venous thrombotic events. In this mini-review, we report the case of a 41-year-old woman without cardiovascular risk factors or a previous history of thrombotic events, admitted for ST-elevation myocardial infarction, in whom coronary angiography showed a thrombotic occlusion in the left anterior descending artery. The patient underwent primary percutaneous coronary intervention (PCI), with GPIIB-IIIA antagonist, then, a pre-dilation with a semi-compliant balloon-catheter, followed by implantation of 2 stents. The etiological assessment revealed a high level of coagulation factor VIII (FVIII). She underwent anticoagulation therapy (with acenocoumarol) with well-controlled international normalised ratio (INR).


Assuntos
Angiografia Coronária , Fator VIII/metabolismo , Intervenção Coronária Percutânea/métodos , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Acenocumarol/administração & dosagem , Adulto , Anticoagulantes/administração & dosagem , Feminino , Humanos , Inibidores da Agregação Plaquetária/administração & dosagem , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/antagonistas & inibidores , Infarto do Miocárdio com Supradesnível do Segmento ST/sangue , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Stents , Trombose/diagnóstico por imagem
14.
BMJ Case Rep ; 14(4)2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33795273

RESUMO

Acute intoxication with a vitamin K antagonist may cause serious coagulopathy. We report the accidental ingestion of a high dose of acenocoumarol in a young child. Two intravenous administrations of 5 mg of vitamin K, in combination with fast and repeated administration of activated charcoal and sodium sulfate, were sufficient to prevent coagulopathy and related symptoms, despite a confirmed elevated blood acenocoumarol concentration (260 µg/L).


Assuntos
Acenocumarol , Transtornos da Coagulação Sanguínea , Acenocumarol/efeitos adversos , Anticoagulantes/efeitos adversos , Transtornos da Coagulação Sanguínea/induzido quimicamente , Transtornos da Coagulação Sanguínea/tratamento farmacológico , Criança , Ingestão de Alimentos , Humanos , Vitamina K
15.
Molecules ; 26(5)2021 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-33800767

RESUMO

Vitamin K antagonists are indicated for the thromboprophylaxis in patients with mechanical prosthetic heart valves (MPHV). However, it is unclear whether some differences between acenocoumarol and warfarin in terms of anticoagulation quality do exist. We included 2111 MPHV patients included in the nationwide PLECTRUM registry. We evaluated anticoagulation quality by the time in therapeutic range (TiTR). Factors associated with acenocoumarol use and with low TiTR were investigated by multivariable logistic regression analysis. Mean age was 56.8 ± 12.3 years; 44.6% of patients were women and 395 patients were on acenocoumarol. A multivariable logistic regression analysis showed that patients on acenocoumarol had more comorbidities (i.e., ≥3, odds ratio (OR) 1.443, 95% confidence interval (CI) 1.081-1.927, p = 0.013). The mean TiTR was lower in the acenocoumarol than in the warfarin group (56.1 ± 19.2% vs. 61.6 ± 19.4%, p < 0.001). A higher prevalence of TiTR (<60%, <65%, or <70%) was found in acenocoumarol users than in warfarin ones (p < 0.001 for all comparisons). Acenocoumarol use was associated with low TiTR regardless of the cutoff used at multivariable analysis. A lower TiTR on acenocoumarol was found in all subgroups of patients analyzed according to sex, hypertension, diabetes, age, valve site, atrial fibrillation, and INR range. In conclusion, anticoagulation quality was consistently lower in MPHV patients on acenocoumarol compared to those on warfarin.


Assuntos
Acenocumarol/uso terapêutico , Anticoagulantes/uso terapêutico , Coagulação Sanguínea/efeitos dos fármacos , Doenças das Valvas Cardíacas/terapia , Próteses Valvulares Cardíacas/efeitos adversos , Tromboembolia Venosa/tratamento farmacológico , Varfarina/uso terapêutico , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tromboembolia Venosa/etiologia
16.
Lancet Neurol ; 20(5): 341-350, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33765420

RESUMO

BACKGROUND: Cervical artery dissection is a major cause of stroke in young people (aged <50 years). Historically, clinicians have preferred using oral anticoagulation with vitamin K antagonists for patients with cervical artery dissection, although some current guidelines-based on available evidence from mostly observational studies-suggest using aspirin. If proven to be non-inferior to vitamin K antagonists, aspirin might be preferable, due to its ease of use and lower cost. We aimed to test the non-inferiority of aspirin to vitamin K antagonists in patients with cervical artery dissection. METHODS: We did a multicentre, randomised, open-label, non-inferiority trial in ten stroke centres across Switzerland, Germany, and Denmark. We randomly assigned (1:1) patients aged older than 18 years who had symptomatic, MRI-verified, cervical artery dissection within 2 weeks before enrolment, to receive either aspirin 300 mg once daily or a vitamin K antagonist (phenprocoumon, acenocoumarol, or warfarin; target international normalised ratio [INR] 2·0-3·0) for 90 days. Randomisation was computer-generated using an interactive web response system, with stratification according to participating site. Independent imaging core laboratory adjudicators were masked to treatment allocation, but investigators, patients, and clinical event adjudicators were aware of treatment allocation. The primary endpoint was a composite of clinical outcomes (stroke, major haemorrhage, or death) and MRI outcomes (new ischaemic or haemorrhagic brain lesions) in the per-protocol population, assessed at 14 days (clinical and MRI outcomes) and 90 days (clinical outcomes only) after commencing treatment. Non-inferiority of aspirin would be shown if the upper limit of the two-sided 95% CI of the absolute risk difference between groups was less than 12% (non-inferiority margin). This trial is registered with ClinicalTrials.gov, NCT02046460. FINDINGS: Between Sept 11, 2013, and Dec 21, 2018, we enrolled 194 patients; 100 (52%) were assigned to the aspirin group and 94 (48%) were assigned to the vitamin K antagonist group. The per-protocol population included 173 patients; 91 (53%) in the aspirin group and 82 (47%) in the vitamin K antagonist group. The primary endpoint occurred in 21 (23%) of 91 patients in the aspirin group and in 12 (15%) of 82 patients in the vitamin K antagonist group (absolute difference 8% [95% CI -4 to 21], non-inferiority p=0·55). Thus, non-inferiority of aspirin was not shown. Seven patients (8%) in the aspirin group and none in the vitamin K antagonist group had ischaemic strokes. One patient (1%) in the vitamin K antagonist group and none in the aspirin group had major extracranial haemorrhage. There were no deaths. Subclinical MRI outcomes were recorded in 14 patients (15%) in the aspirin group and in 11 patients (13%) in the vitamin K antagonist group. There were 19 adverse events in the aspirin group, and 26 in the vitamin K antagonist group. INTERPRETATION: Our findings did not show that aspirin was non-inferior to vitamin K antagonists in the treatment of cervical artery dissection. FUNDING: Swiss National Science Foundation, Swiss Heart Foundation, Stroke Funds Basel, University Hospital Basel, University of Basel, Academic Society Basel.


Assuntos
Anticoagulantes/uso terapêutico , Aspirina/uso terapêutico , Dissecação da Artéria Carótida Interna/tratamento farmacológico , Inibidores da Agregação Plaquetária/uso terapêutico , Dissecação da Artéria Vertebral/tratamento farmacológico , Acenocumarol/uso terapêutico , Adulto , Dissecação da Artéria Carótida Interna/complicações , Dissecação da Artéria Carótida Interna/diagnóstico por imagem , Dinamarca , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Femprocumona/uso terapêutico , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/epidemiologia , Suíça , Dissecação da Artéria Vertebral/complicações , Dissecação da Artéria Vertebral/diagnóstico por imagem , Varfarina/uso terapêutico
17.
Hellenic J Cardiol ; 62(3): 234-240, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32683128

RESUMO

BACKGROUND: To estimate the incidence of hemorrhagic events in patients with atrial fibrillation (AF) treated with acenocoumarol, and the management cost of those requiring hospitalization in Greece. METHODS: A nationwide telephone survey was conducted between December 2017 and January 2018, to identify cardiologists who treat AF patients with acenocoumarol. A total of 300 cardiologists were selected and reported the number of AF acenocoumarol-treated patients during the past 12 months and the number of those who experienced a hemorrhagic event. The hospital charges to sickness fund and the cost of resource utilization of AF patients hospitalized between January 2013 and June 2017 at a tertiary hospital in Athens due to acenocoumarol-related bleedings were retrieved. RESULTS: Out of 48,255 AF patients, 12,633 (26.2%) were treated with acenocoumarol. In all, 5.1% of patients experienced a hemorrhagic event with the incidence of bleeding requiring hospitalization being 1.7%. The most common bleeding site was the gastrointestinal system (51.5%). The mean (95% CI) management cost per bleeding event requiring hospitalization was €1,202 (€1,058-€1,420). The higher cost was that of intracranial bleeding €3,887 (€2,700-€5,046). The expected annual economic burden for the management of bleedings related to acenocoumarol and requiring hospitalization was estimated at €1,463,955. CONCLUSIONS: The incidence of bleeding events in AF acenocoumarol-treated patients in Greece as well as the estimated annual economic burden for the management of bleeding events requiring hospitalization, emphasize the need to comply with the current guidelines and to optimize therapeutic strategies for the management of AF side effects with oral anticoagulants, particularly in patients with high bleeding risk.


Assuntos
Fibrilação Atrial , Acidente Vascular Cerebral , Acenocumarol/efeitos adversos , Anticoagulantes/efeitos adversos , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/epidemiologia , Grécia/epidemiologia , Hospitalização , Humanos , Incidência , Estudos Retrospectivos
19.
Br J Clin Pharmacol ; 87(2): 632-643, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32530052

RESUMO

AIMS: Acenocoumarol is a vitamin-K antagonist (VKA) primarily used in certain countries (e.g. India, Netherlands, Spain). The half-life of acenocoumarol is similar to that of non-VKA oral anticoagulants (NOAC), unlike warfarin, and this could affect comparative effectiveness and safety (CES). However, data on CES for NOAC come almost exclusively from studies using warfarin as the comparator. We aimed to assess outcomes of NOAC and acenocoumarol in people with non-valvular atrial fibrillation (NVAF) in real-world clinical practice. METHODS: This is a population-based retrospective cohort study. All new users of oral anticoagulants from November 2011 to December 2015 with NVAF were included (n = 41,560). Data were obtained by linking several health electronic records of the Valencia region, Spain. Incidence rates were estimated. We used the inverse probability of treatment weighted Cox analysis to control for indication bias when assessing the risk of effectiveness and safety outcomes for each NOAC compared with acenocoumarol. Several sensitivity analyses were performed. RESULTS: We did not find differences in the risk of mortality, ischaemic stroke or any gastrointestinal bleeding. However, we did find a decreased risk of intracranial haemorrhage for dabigatran (HR: 0.34, 95% CI 0.20-0.56) and rivaroxaban (HR: 0.55, 95% CI 0.35-0.85) as compared to acenocoumarol. In subanalyses, apixaban showed a higher risk of ischaemic stroke in high-risk persons (≥75 years and CHA2DS2-VASC score ≥ 2). CONCLUSIONS: No differences in clinical outcomes were found between NOAC and acenocoumarol overall, although dabigatran and rivaroxaban showed a lower risk of intracranial haemorrhage. Findings on the potential inferiority of specific NOAC in high-risk subgroups should be studied further.


Assuntos
Fibrilação Atrial , Isquemia Encefálica , Acidente Vascular Cerebral , Acenocumarol/efeitos adversos , Administração Oral , Anticoagulantes/efeitos adversos , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/epidemiologia , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/epidemiologia , Isquemia Encefálica/prevenção & controle , Estudos de Coortes , Dabigatrana/efeitos adversos , Humanos , Índia , Países Baixos , Estudos Retrospectivos , Rivaroxabana/efeitos adversos , Espanha/epidemiologia , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/prevenção & controle
20.
Eur J Clin Invest ; 51(1): e13356, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33180323

RESUMO

BACKGROUND: Splanchnic vein thrombosis (SVT) is an uncommon but potentially life-threatening disease usually related to different underlying clinical conditions. The risk of SVT recurrences is high over time in patients with an underlying permanent prothrombotic condition. Vitamin K antagonists (VKA) represent the mainstay of treatment for SVT. Data about the efficacy and safety of direct oral anticoagulants (DOACs) are reported in the literature for the treatment of acute SVT, but less is known about their application for the secondary prophylaxis of venous thromboembolism (VTE). The aim of this study was to assess the efficacy and safety of long-term DOACs therapy in patients at high-risk of thrombosis, compared to VKA. METHODS: This is a retrospective single-centre study including 70 patients with SVT on long-term anticoagulant treatment with VKA followed-up at our Units between January 2017 and December 2019. All the patients were at high thrombotic risk defined as the presence of a permanent prothrombotic condition requiring long-term anticoagulation. During follow-up, 28 patients were shifted to DOACs and their clinical outcomes were compared to those of the patients who continued VKA therapy. All the arterial and venous thrombotic events of the splanchnic and extra-splanchnic districts as well as the haemorrhagic adverse events occurring during follow-up were recorded. RESULTS: Of the seventy patients enrolled in the study, 36 patients (51.4%) had a single-segment involvement thrombosis (28.5% of portal vein, 7.1% of superior mesenteric vein, 4.3% of splenic vein, 11.5% of hepatic veins) and 34 patients (48.6%) had multi-segment involvement at the time of diagnosis. 42 patients (60%) continued VKA therapy and 28 (40%) were switched to DOACs. Median follow-up was 6 years (range 2-8) during VKA and 1.9 years (range 1-5.2) during DOACs. The incidence of thrombotic events was similar between patients on VKA and those on DOACs. Patients on VKA developed deep vein thrombosis (DVT), and of the patients on DOACs 1 developed NSTEMI and 1 DVT. No major haemorrhagic events occurred. Minor bleedings occurred in 26% of patients on VKA and in none of the DOACs patients (P: 0.09). CONCLUSIONS: Our results highlight that DOACs could represent an effective and safe alternative to the VKA for secondary prophylaxis in SVT patients at high risk of thrombosis.


Assuntos
Inibidores do Fator Xa/uso terapêutico , Hemorragia/induzido quimicamente , Isquemia Mesentérica/tratamento farmacológico , Veia Porta , Trombose Venosa/tratamento farmacológico , Acenocumarol/uso terapêutico , Adulto , Anticoagulantes/uso terapêutico , Síndrome de Budd-Chiari/tratamento farmacológico , Duração da Terapia , Feminino , Hemorragia/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Pirazóis/uso terapêutico , Piridinas/uso terapêutico , Piridonas/uso terapêutico , Rivaroxabana/uso terapêutico , Prevenção Secundária , Tiazóis/uso terapêutico , Varfarina/uso terapêutico
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