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1.
PLoS One ; 15(11): e0242922, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33253294

RESUMO

BACKGROUND: Although randomized trials provide a high level of evidence regarding the efficacy of non-vitamin K oral anticoagulants (NOACs), the results of such trials may differ from those observed in day-to-day clinical practice. AIMS: To compare the risk of stroke/systemic embolism (S/SE) and major bleeding (MB) between NOAC and warfarin in clinical practice. METHODS: Patients with non-valvular atrial fibrillation (NVAF) who started warfarin/NOACs between January 2015 and November 2016 were retrospectively identified from Korea's nationwide health insurance claims database. Using inpatient diagnosis and imaging records, the Cox models with inverse probability of treatment weighting using propensity scores were used to estimate hazard ratios (HRs) for NOACs relative to warfarin. RESULTS: Of the 48,389 patients, 10,548, 11,414, 17,779 and 8,648 were administered apixaban, dabigatran, rivaroxaban and warfarin, respectively. Many patients had suffered prior strokes (36.7%, 37.7%, 31.4%, and 32.2% in apixaban, dabigatran, rivaroxaban, and warfarin group, respectively), exhibited high CHA2DS2-VASc (4.8, 4.6, 4.6, and 4.1 in apixaban, dabigatran, rivaroxaban, and warfarin group, respectively) and HAS-BLED (3.7, 3.6, 3.6, and 3.3 in apixaban, dabigatran, rivaroxaban, and warfarin group, respectively) scores, had received antiplatelet therapy (75.4%, 75.7%, 76.8%, and 70.1% in apixaban, dabigatran, rivaroxaban, and warfarin group, respectively), or were administered reduced doses of NOACs (49.8%, 52.9%, and 42.8% in apixaban, dabigatran, and rivaroxaban group, respectively). Apixaban, dabigatran and rivaroxaban showed a significantly lower S/SE risk [HR, 95% confidence intervals (CI): 0.62, 0.54-0.71; 0.60, 0.53-0.69; and 0.71, 0.56-0.88, respectively] than warfarin. Apixaban and dabigatran (HR, 95% CI: 0.58, 0.51-0.66 and 0.75, 0.60-0.95, respectively), but not rivaroxaban (HR, 95% CI: 0.84, 0.69-1.04), showed a significantly lower MB risk than warfarin. CONCLUSIONS: Among Asian patients who were associated with higher bleeding risk, low adherence, and receiving reduced NOAC dose than that provided in randomised controlled trials, all NOACs were associated with a significantly lower S/SE risk and apixaban and dabigatran with a significantly lower MB risk than warfarin.


Assuntos
Anticoagulantes/administração & dosagem , Fibrilação Atrial/tratamento farmacológico , Hemorragia/tratamento farmacológico , Acidente Vascular Cerebral/tratamento farmacológico , Administração Oral , Adulto , Idoso , Anticoagulantes/efeitos adversos , Fibrilação Atrial/complicações , Fibrilação Atrial/patologia , Dabigatrana/administração & dosagem , Embolia/complicações , Embolia/tratamento farmacológico , Embolia/epidemiologia , Embolia/patologia , Feminino , Hemorragia/complicações , Hemorragia/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Pirazóis/administração & dosagem , Piridonas/administração & dosagem , Rivaroxabana/administração & dosagem , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/epidemiologia , Vitamina K/antagonistas & inibidores , Varfarina/administração & dosagem
2.
Am J Emerg Med ; 38(10): 2096-2100, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33152586

RESUMO

INTRODUCTION: Previous studies have shown fixed-dose 4PCC to be as effective as standard-dose 4PCC for warfarin reversal. However, certain patient populations such as those with high total body weight (TBW) or elevated baseline INR may be at increased risk for treatment failure. The purpose of this study was to validate the efficacy of a novel fixed-dose 4PCC protocol for warfarin reversal. METHODS: This was a multi-centered observational comparison of patients who received 4PCC for warfarin reversal. Fixed-dose patients received 1500 units of 4PCC with the dose increased to 2000 units in patients with a baseline INR ≥ 7.5, a TBW ≥ 100 kg, or for intracranial hemorrhage (ICH). Standard-dosing followed manufacturer recommendations. The primary outcome was achievement of a post-4PCC INR of ≤1.4. Secondary outcomes included target INR achievement among patients with a baseline INR ≥ 7.5, a TBW ≥ 100 kg, or neurologic bleeding indications; hospital length of stay; cost of therapy; and thromboembolic complications. RESULTS: A total of 116 patients were included in the standard-dose group and 75 in the fixed-dose group. There was no difference in the primary outcome (65% vs 57%, p = 0.32). There was no difference in secondary outcomes aside from cost of therapy in which fixed-dose 4PCC was less expensive than standard-dose 4PCC. CONCLUSION: A fixed-dose 4PCC regimen for warfarin reversal of 1500 units, with an increased dose of 2000 units for select patients, is as effective as standard-dose 4PCC for INR reversal.


Assuntos
Fatores de Coagulação Sanguínea/uso terapêutico , Hemorragia/tratamento farmacológico , Varfarina/antagonistas & inibidores , Idoso , Idoso de 80 Anos ou mais , Fatores de Coagulação Sanguínea/farmacologia , Distribuição de Qui-Quadrado , Feminino , Hemorragia Gastrointestinal/tratamento farmacológico , Hemorragia Gastrointestinal/fisiopatologia , Hemorragia/fisiopatologia , Humanos , Hemorragias Intracranianas/tratamento farmacológico , Hemorragias Intracranianas/fisiopatologia , Masculino , Pessoa de Meia-Idade , Varfarina/efeitos adversos , Varfarina/uso terapêutico
3.
Ann Hematol ; 99(12): 2763-2771, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32918114

RESUMO

The current standard of care treatment for severe hemophilia A and B (SHA and SHB) is the prophylactic intravenous replacement of coagulation factor VIII or IX (FVIII/FIX) to prevent spontaneous bleeding. Persons with hemophilia without prophylactic treatment receive therapy in case of bleeding, i.e., on demand. To assess treatment patterns, utilization of products, and bleeding outcomes in a real-world cohort of persons with SHA and SHB, defined as FVIII or FIX activity < 1%, data was retrospectively collected from hemophilia-specific patient diaries used for home treatment, medical records, and entries into the Austrian Hemophilia Registry from the year 2012 to 2017. Fifty-three male persons with SHA (n = 47) and SHB (n = 6) were included; 26 with SHA and 5 with SHB were on prophylaxis, 8 and 1 switched therapy regimen, and 13 and 0 received on-demand therapy. Persons on prophylaxis used a mean factor FVIII or FIX dose of 71.7 and 40.1 IU/kg/week. Median (IQR) annualized bleeding rates (ABR) in SHA were 28.0 (23.4-31.3) in the on-demand, 4.9 (1.6-13.5) in the prophylaxis group, and 3.0 (2.0-6.8) in the prophylactic group of SHB. Three persons with SHA had zero bleeds during the observation period. On-demand therapy and hepatitis B and C were associated with higher ABR but not age, weight, and HIV positivity. Bleeding rates and the proportion of on-demand therapy in persons with hemophilia were high in our real-world cohort. Further improvement is needed, which might be facilitated with the advent of factor products with extended half-life or non-factor therapies.


Assuntos
Fator IX/administração & dosagem , Fator VIII/administração & dosagem , Hemofilia A/tratamento farmacológico , Hemofilia B/tratamento farmacológico , Hemorragia/tratamento farmacológico , Índice de Gravidade de Doença , Adulto , Áustria/epidemiologia , Estudos de Coortes , Hemofilia A/diagnóstico , Hemofilia A/epidemiologia , Hemofilia B/diagnóstico , Hemofilia B/epidemiologia , Hemorragia/diagnóstico , Hemorragia/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
4.
Ann Hematol ; 99(12): 2787-2800, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32879992

RESUMO

Significant advancements have been achieved with regard to the outcomes of acute promyelocytic leukemia (APL) patients through the introduction of all-trans retinoic acid; however, early hemorrhagic death and differentiation syndrome remain the major causes of remission induction failure in patients with APL. To investigate early death, serious hemorrhage, and differentiation syndrome during remission induction therapy in terms of incidence, risk factors, influence on outcomes, and prophylactic effects of several new anticoagulants, the results of 344 patients enrolled in the Acute Promyelocytic Leukemia 204 study conducted by the Japan Adult Leukemia Study Group were analyzed. Early death was observed in 16 patients (4.7%), of whom 14 had serious hemorrhage and 2 had differentiation syndrome. Serious hemorrhage and differentiation syndrome of grade 2 or higher were observed in 21 and 54 patients, respectively. Patients who achieved complete remission had a 7-year disease-free survival of 84.8% if they did not experience serious hemorrhage and 40.0% if they experienced serious hemorrhage during remission induction therapy (P = 0.001). Risk factor analyses showed that higher white blood cell count was associated with early death, higher white blood cell count and lower platelet count with serious hemorrhage, and leukocytosis during induction therapy and higher body surface area with differentiation syndrome. In conclusion, these results indicate that patients with such high-risk features may benefit from more intensive supportive care. The hemorrhagic risk was not relieved by the introduction of new anticoagulants. Further studies are required to establish the predictive impact of body surface area on differentiation syndrome. This trial is registered with UMIN-CTR as C000000154 on September 13, 2005.


Assuntos
Diferenciação Celular/fisiologia , Hemorragia/diagnóstico , Hemorragia/mortalidade , Leucemia Promielocítica Aguda/diagnóstico , Leucemia Promielocítica Aguda/mortalidade , Índice de Gravidade de Doença , Adolescente , Adulto , Idoso , Anticoagulantes/farmacologia , Anticoagulantes/uso terapêutico , Diferenciação Celular/efeitos dos fármacos , Feminino , Hemorragia/tratamento farmacológico , Humanos , Japão , Leucemia Promielocítica Aguda/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Mortalidade/tendências , Valor Preditivo dos Testes , Estudos Prospectivos , Indução de Remissão/métodos , Adulto Jovem
5.
Vnitr Lek ; 66(4): 225-231, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32972179

RESUMO

Low molecular weight heparin (LMWH) has become a standard of treatment of cancer-associated thromboembolism (CAT). Until recently, direct oral anticoagulants (DOAC) have not had data about efficacy and safety in cancer patients. However, in the last two years, four randomized open-label studies comparing DOAC and LMWH in the treatment of CAT have been published. The first one was a large trial with edoxaban, followed by two smaller studies with rivaroxaban and apixaban, and, recently, by another large trial with apixaban. There are some differences among the studies concerning design, inclusion and exclusion criteria, length of treatment. In summary, DOAC are associated with a trend to the reduction of the risk of recurrence of venous thromboembolism; however, this is at the expense of some increase in bleeding risk. This risk is differential; the prevailing site of bleeding is the upper part of gastrointestinal tract, and, to a lesser extent, genitourinary tract. The updated guidelines for the treatment of CAT suggest DOAC as an alternative, however with careful consideration of the risk of bleeding and the risk of drug interactions. So far, the guidelines have mentioned edoxaban and rivaroxaban. With emerging evidence, apixaban is expected to play a role as well.


Assuntos
Neoplasias , Tromboembolia Venosa , Administração Oral , Anticoagulantes/uso terapêutico , Hemorragia/induzido quimicamente , Hemorragia/tratamento farmacológico , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/prevenção & controle
6.
BMC Infect Dis ; 20(1): 658, 2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32912165

RESUMO

BACKGROUND: Stenotrophomonas maltophilia-induced pulmonary haemorrhage is considered a fatal infection among haematological patients. The outcome can be explained by the patients' immunity status and late diagnosis and treatment. CASE PRESENTATION: We present the rare case of successful outcome in a 61-year-old female who developed alveolar haemorrhage and acute respiratory distress syndrome 8 days after a chemotherapy session for her acute lymphoblastic leukaemia, in the context of secondary bone marrow aplasia. Stenotrophomonas maltophilia was isolated in sputum culture. The patient benefitted from early empirical treatment with colistin followed by trimethoprim/sulfamethoxazole, according to the antibiogram. Despite a severe initial clinical presentation in need of mechanical ventilation, neuromuscular blocking agents infusion, and ventilation in prone position, the patient had a favourable outcome and was discharged from intensive care after 26 days. CONCLUSIONS: Stenotrophomonas maltophilia severe pneumonia complicated with pulmonary haemorrhage is not always fatal in haematological patients. Empirical treatment of multidrug-resistant Stenotrophomonas maltophilia in an immunocompromised haematological patient presenting with hemoptysis should be taken into consideration.


Assuntos
Antibacterianos/uso terapêutico , Colistina/uso terapêutico , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Hemorragia/tratamento farmacológico , Pneumonia Bacteriana/tratamento farmacológico , Síndrome do Desconforto Respiratório do Adulto/tratamento farmacológico , Stenotrophomonas maltophilia/isolamento & purificação , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/complicações , Feminino , Infecções por Bactérias Gram-Negativas/etiologia , Hemorragia/etiologia , Humanos , Hospedeiro Imunocomprometido , Pessoa de Meia-Idade , Pneumonia Bacteriana/etiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Alvéolos Pulmonares/patologia , Síndrome do Desconforto Respiratório do Adulto/etiologia , Síndrome do Desconforto Respiratório do Adulto/microbiologia , Escarro/microbiologia , Resultado do Tratamento
7.
Mayo Clin Proc ; 95(8): 1604-1612, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32753135

RESUMO

OBJECTIVE: To present our center's experience with a maintenance treatment algorithm for intravenous bevacizumab that allows for personalized therapy decisions. PATIENTS AND METHODS: We reviewed all patients treated with intravenous bevacizumab for hereditary hemorrhagic telangiectasia-related bleeding and/or high-output cardiac failure (HOCF) from January 1, 2013, to July 1, 2019, at the Mayo Clinic, Rochester, Minnesota. Data regarding subsequent bevacizumab dosing were abstracted. RESULTS: A total of 57 patients (n=40, 70.2% females) were identified with a median age of 65 (55 to 74; range, 37 to 89) years. High-cardiac output state was present in 21 patients (36.8%) and 10 (17.5%) were treated with intravenous bevacizumab primarily for HOCF. The median duration of follow-up after completion of the initial intravenous bevacizumab treatment was 25 (12.3 to 40.8; range, 0.1 to 65.4) months. A total of 20 (35.1%) patients with a median follow-up of 13.5 (range, 0 to 48.4) months required no maintenance dosing throughout the duration of follow-up. Among those who required subsequent maintenance doses, only a small fraction (8 patients; 14.0%) required regular maintenance doses every 4 to 8 weeks during follow-up whereas the majority of patients required intermittent "as-needed" doses at varying intervals. CONCLUSION: There is significant inter-individual variability in the need for maintenance intravenous bevacizumab when patients are followed using a predefined bevacizumab maintenance dosing treatment algorithm. The use of "as-needed" maintenance bevacizumab appears to be an effective strategy for management of hereditary hemorrhagic telangiectasia-related bleeding and HOCF.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Bevacizumab/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Hemorragia/tratamento farmacológico , Telangiectasia Hemorrágica Hereditária/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/administração & dosagem , Bevacizumab/administração & dosagem , Feminino , Insuficiência Cardíaca/etiologia , Hemorragia/etiologia , Humanos , Individualidade , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Medicina de Precisão/métodos , Estudos Retrospectivos , Telangiectasia Hemorrágica Hereditária/complicações
8.
Am J Emerg Med ; 38(9): 1890-1903, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32750627

RESUMO

Anticoagulation is key to the treatment/prevention of thromboembolic events. The primary complication of anticoagulation is serious or life-threatening hemorrhage, which may necessitate prompt anticoagulation reversal; this could also be required for nonbleeding patients requiring urgent/emergent invasive procedures. The decision to reverse anticoagulation should weigh the benefit-risk ratio of supporting hemostasis versus post-reversal thrombosis. We appraise the available guidelines/recommendations for vitamin K antagonist (VKA) and direct oral anticoagulant (DOAC) reversal in the management of major bleeding, and also assess recent clinical data that may not yet be reflected in official guidance. In general, available guidelines are consistent in their recommendations, advocating administration of vitamin K and 4-factor prothrombin complex concentrates (4F-PCCs) rather than fresh frozen plasma to patients with VKA-associated intracranial hemorrhage and life-threatening bleeding, and specific reversal agents as essential therapy for DOAC reversal in those same severe conditions. However, guidelines also recommend off-label use of PCCs for DOAC reversal when specific reversal agents are unavailable. Limited recent evidence generally support the latter recommendation, but guidelines are likely to evolve as more data become available.


Assuntos
Anticoagulantes , Guias de Prática Clínica como Assunto , Vitamina K/antagonistas & inibidores , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Consenso , Hemorragia/induzido quimicamente , Hemorragia/tratamento farmacológico , Humanos
9.
West J Emerg Med ; 21(4): 924-934, 2020 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-32726266

RESUMO

INTRODUCTION: Current U.S. cardiology guidelines recommend oral anticoagulation (OAC) to reduce stroke risk in selected patients with atrial fibrillation (AF), but no formal AF OAC recommendations exist to guide emergency medicine clinicians in the acute care setting. We sought to characterize emergency department (ED) OAC prescribing practices after an ED AF diagnosis. METHODS: This retrospective study included index visits for OAC-naive patients ≥18 years old who were discharged home from the ED at an urban, academic, tertiary hospital with a primary diagnosis of AF from 2012-2014. Five hypothesis-blinded, chart reviewers abstracted data from patient problem lists and medical history in the electronic health record to assess stroke (CHA2DS2-VASc) and bleeding risk (HAS-BLED). The primary outcome was the provision of an OAC prescription at discharge in OAC-naive patients with high stroke risk. Descriptive statistics and multivariable logistic regression assessed associations between OAC prescription and patient characteristics. RESULTS: We included 138 patient visits in our analysis, of whom 39.9% (n = 55) were low stroke risk (CHA2DS2-VASc = 0 in males and 1 in females), 15.9% (n = 22) were intermediate risk (CHA2DS2-VASc = 1 in males), and 44.2% (n = 61) were high risk (CHA2DS2-VASc ≥ 2). Of patients with high stroke risk and low-to-intermediate bleeding risk (n = 57), 80.7% were not prescribed an OAC at discharge. Cardiology consultation and female gender, but not stroke risk (CHA2DS2-VASc score), were predictors of an ED provider prescribing an OAC to an OAC-naive AF patient at ED discharge. CONCLUSION: The majority of OAC-eligible patients were discharged home without an OAC prescription. In OAC-naive patients discharged home from the ED, cardiology consultation and female gender were associated with OAC prescription. Our findings suggest that access to expert opinion may improve provider comfort with OAC prescribing and highlight the need for improved guidelines specific to ED-management of AF.


Assuntos
Anticoagulantes/administração & dosagem , Fibrilação Atrial/tratamento farmacológico , Prescrições de Medicamentos , Serviço Hospitalar de Emergência , Alta do Paciente , Lacunas da Prática Profissional , Administração Oral , Adulto , Idoso , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Feminino , Hemorragia/tratamento farmacológico , Hemorragia/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/etiologia , Resultado do Tratamento
10.
Stroke Vasc Neurol ; 5(2): 128-137, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32606085

RESUMO

BACKGROUND: The effect of cerebral small vessel disease (CSVD) and intracranial arterial stenosis (ICAS) on stroke outcomes remains unclear. METHODS: Data of 1045 patients with minor stroke or transient ischaemic attack (TIA) were obtained from 45 sites of the Clopidogrel in High-Risk Patients with Acute Non-disabling Cerebrovascular Events (CHANCE) trial. We assessed the associations of burdens of CSVD and ICAS with new strokes and bleeding events using multivariate Cox regression models and those with modified Rankin Scale (mRS) scores using ordinal logistic regression models. RESULTS: Among the 1045 patients, CSVD was present in 830 cases (79.4%) and ICAS in 460 (44.0%). Patients with >1 ICAS segment showed the highest risk of new strokes (HR 2.03, 95% CI 1.15 to 3.56, p=0.01). No association between CSVD and the occurrence of new strokes was found. The presence of severe CSVD (common OR (cOR) 2.01, 95% CI 1.40 to 2.89, p<0.001) and >1 ICAS segment (cOR 2.15, 95% CI 1.57 to 2.93, p<0.001) was associated with higher mRS scores. Severe CSVD (HR 10.70, 95% CI 1.16 to 99.04, p=0.04), but not ICAS, was associated with a higher risk of bleeding events. Six-point modified CSVD score improved the predictive power for bleeding events and disability. INTERPRETATION: CSVD is associated with more disability and bleeding events, and ICAS is associated with an increased risk of stroke and disability in patients with minor stroke and TIA at 3 months. CSVD and ICAS may represent different vascular pathologies and play distinct roles in stroke outcomes. TRIAL REGISTRATION NUMBER: NCT00979589.


Assuntos
Doenças de Pequenos Vasos Cerebrais/complicações , Arteriosclerose Intracraniana/complicações , Ataque Isquêmico Transitório/etiologia , Acidente Vascular Cerebral/etiologia , Idoso , Angiografia Cerebral , Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Doenças de Pequenos Vasos Cerebrais/tratamento farmacológico , China , Clopidogrel/uso terapêutico , Imagem de Difusão por Ressonância Magnética , Avaliação da Deficiência , Método Duplo-Cego , Feminino , Hemorragia/tratamento farmacológico , Hemorragia/etiologia , Humanos , Arteriosclerose Intracraniana/diagnóstico por imagem , Arteriosclerose Intracraniana/tratamento farmacológico , Ataque Isquêmico Transitório/diagnóstico , Angiografia por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/uso terapêutico , Prognóstico , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/tratamento farmacológico
11.
Medicine (Baltimore) ; 99(26): e20851, 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32590782

RESUMO

INTRODUCTION: The Antopol-Goldman lesion (AGL), which expresses subepithelial hemorrhage in the renal pelvis, was first defined by Antopol and Goldman in 1948. The objective of this study is to report the first case of AGL in patients with congenital hemophilia and review the relevant literature. PATIENT CONCERNS: A 32-year-old male patient diagnosed with congenital hemophilia A (FVIII = %4) with high responding inhibitors (7.4 BU) was admitted to our emergency department with gross hematuria and sudden onset flank pain. DIAGNOSIS: Abdominal computed tomography (CT-scan) presented a hyperdense lesion in the left ureteropelvic junction with Hounsfield Units of 56 compatibles with hemorrhage. INTERVENTIONS: The patient was given 4500 IU of factor eight inhibitor bypass activity (FEIBA) intravenously twice daily for 5 days. Subsequently, 4500 IU of FEIBA was administrated once a day for 2 days. OUTCOMES: The patient's complaints disappeared on the fourth day of treatment. Macroscopic and microscopic hematuria was not seen in the following days. Follow-up CT was done 3 months after discharge and showed normal left renal pelvis without hyperdenosis. Follow-up CT was performed 3 months after discharge and presented normal left renal pelvis with no hyperdense lesion. CONCLUSION: Although very rare, AGL should be kept in mind in the differential diagnosis of renal pelvic hemorrhage. In the patient who has an underlying history of coagulopathy nephrectomy can be avoided when there is awareness of AGL.


Assuntos
Hemofilia A/complicações , Hemorragia/etiologia , Administração Intravenosa , Adulto , Fatores de Coagulação Sanguínea/uso terapêutico , Hematúria/etiologia , Hemorragia/tratamento farmacológico , Hemorragia/prevenção & controle , Humanos , Pelve Renal/anormalidades , Pelve Renal/fisiopatologia , Masculino , Tomografia Computadorizada por Raios X/métodos , Ureter/anormalidades , Ureter/fisiopatologia
13.
Toxicon ; 184: 99-108, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32522619

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: In the region of Western Pará, Amazonia, Brazil, Philodendron megalophyllum is widely used for the treatment of envenomations caused by bites from venomous snakes. The traditional use of plants is usually done through oral administration of an infusion (decoction) soon after the bite occurs. The efficiency of aqueous extracts of P. megalophyllum was demonstrated for blocking the activity of the venom of Bothrops sp., but only for a pre-incubation protocol (venom:extract), which fails to simulate the real form of use of this species. In this context, the objective of this research was to evaluate the anti-snakebite potential of the aqueous extract of P. megalophyllum to inhibit for the biological activity induced by Bothrops atrox venom (BaV) using traditional treatment methods. MATERIAL AND METHODS: Initially, an aqueous extract using the stem of P. megalophyllum (AEPm) was prepared following the standard procedure used by the residents of the rural area along the Tapajós River (Eixo Forte region) in Santarém, PA, Brazil. The phytochemical profile of AEPm was conducted using thin layer chromatography (TLC) and phenolic compounds were quantified through colorimetric trials. The cytotoxicity of AEPm was evaluated using the MRC-5 human fibroblast line, and the antioxidant potential was measured using DPPH methods and cell culture. AEPm antimicrobial action was evaluated by the 96-well plate microdilution and the minimum inhibitory concentration (MIC) methods using 18 types of microorganisms including bacteria that are present in the oral cavity of snakes. AEPm blocking potential was tested against BaV activity in vitro (fibrinolytic) and in vivo (defibrinating and hemorrhagic). In order to test for an interaction between BaV and AEPm SDS-PAGE electrophoresis was conducted. RESULTS: The presence of coumarins, fatty acids, and hydrolysable tannins were detected in the AEPm. The colorimetric trials showed that AEPm had a high concentration of condensed tannins (20.1 ± 1.2%). The potential of AEPm for blocking of hemorrhagic and fibrinolytic activity of BaV showed a maximum reduction of 86.1% and 96.5%, respectively, for the pre-incubation protocol (1:10, venom:extract). However, when the extract was administered orally there was no significant blocking of these activities. The interaction of BaV and AEPm showed a modification of the profile of proteic bands when compared to the pattern of bands obtained from the BaV alone. The AEPm was not considered toxic, demonstrated antioxidant activity, and was capable of reducing the growth of 10 of the 18 studied microorganisms. CONCLUSION: Although the stem of P. megalophyllum is indicated by traditional medicine techniques as effective against snakebites, the extract, when tested orally was not able to significantly inhibit (p ˃ 0.05) hemorrhage and defibrinating activity induced by the B. atrox venom. On the other hand, the extract yielded a promising result with respect to antioxidant and antimicrobial potential, and after further studies it could be used as a complementary treatment for localized action and secondary infections that frequently occur with snakebites from the genus of Bothrops sp.


Assuntos
Antibacterianos/uso terapêutico , Extratos Vegetais/uso terapêutico , Mordeduras de Serpentes/tratamento farmacológico , Animais , Antibacterianos/farmacologia , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Antivenenos/uso terapêutico , Venenos de Crotalídeos , Hemorragia/tratamento farmacológico , Humanos , Medicina Tradicional , Philodendron , Extratos Vegetais/farmacologia
14.
Hematol Oncol ; 38(4): 589-596, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32588912

RESUMO

The anticoagulant treatment for patients with hematologic malignancies is low molecular weight heparin (LMWH), which is considered the safest in this particular patients setting. Although direct oral anticoagulants (DOACs) have proven their efficacy and safety in patients with cancer, their use can be challenging in patients with hematologic malignancies due to the peculiarity of these neoplasms: high thrombotic risk, possible onset of thrombocytopenia and concomitant anticancer therapies. The aim of our study was to evaluate the efficacy and safety of DOACs for venous thromboembolism or atrial fibrillation in patients with hematologic malignancies and plasmatic DOACs level during anticancer therapy and at time of bleeding or thrombotic complications. We evaluated patients with hematologic malignancies treated with DOACs for venous thromboembolism or atrial fibrillation-therapy was maintained until the platelet count was ≥50 × 109 /L. In case of concomitant anticancer treatment and haemorrhagic or thrombotic events, we checked DOACs plasma levels (trough and peak). The patients evaluated were 135: 104/135 were on anticancer therapy. We did not observe either thrombotic or major haemorrhagic adverse events. Minor bleedings occurred in 10 patients and clinical relevant non-major (CRNM) in two patients. There was a statistically significant correlation between bleedings and myelodysplastic syndrome. DOACs resulted effective and safe in patients with hematologic malignancies. DOACs plasma level can be helpful in suggesting an early dose adjustment to prevent haemorrhagic adverse event in patients on concomitant anticancer therapy. Larger prospective studies including hematologic patients are warranted to confirm the safety and efficacy of DOACs.


Assuntos
Anticoagulantes/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Fibrilação Atrial/tratamento farmacológico , Neoplasias Hematológicas/tratamento farmacológico , Hemorragia/tratamento farmacológico , Tromboembolia Venosa/tratamento farmacológico , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/induzido quimicamente , Fibrilação Atrial/patologia , Feminino , Seguimentos , Neoplasias Hematológicas/patologia , Hemorragia/induzido quimicamente , Hemorragia/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Tromboembolia Venosa/induzido quimicamente , Tromboembolia Venosa/patologia
15.
Carbohydr Polym ; 239: 116106, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32414437

RESUMO

Hemorrhage remains a big threat to trauma patients, especially in combat fields. Therefore, we formulated a biocompatible and biopolymer based chitosan/carrageenan composite dressing. This dressing was fabricated using freeze-drying that will serve as a promising material to promote hemostasis and tissue growth required during hemorrhage. The efficacy of dressing was evaluated for its physiochemical analysis, surface morphology, and biodegradability. Further, human dermal fibroblast cells were seeded on dressing and demonstrated non-toxic effects on the cells by showing enhanced cell attachment and proliferation. In vitro hemostatic properties of the dressing were analyzed by human Thrombin-Antithrombin assay. The dressing formed showed steady blood coagulation implying red blood cells and platelet adhesion that helped in thrombin formation, which is responsible for enhancing wound healing. Thus, it is concluded that the composite dressing can be a potent combination to accelerate hemostatic activity against hemorrhage and promote tissue growth for effective wound healing.


Assuntos
Materiais Biocompatíveis/farmacologia , Lesões Encefálicas Traumáticas/tratamento farmacológico , Carragenina/farmacologia , Quitosana/farmacologia , Citotoxinas/farmacologia , Hemorragia/tratamento farmacológico , Hemostáticos/farmacologia , Cicatrização/efeitos dos fármacos , Bandagens , Materiais Biocompatíveis/química , Coagulação Sanguínea/efeitos dos fármacos , Lesões Encefálicas Traumáticas/patologia , Carragenina/química , Quitosana/química , Citotoxinas/química , Hemorragia/patologia , Hemostáticos/química , Humanos , Tamanho da Partícula , Propriedades de Superfície
16.
Medicine (Baltimore) ; 99(20): e20284, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32443373

RESUMO

INTRODUCTION: Alveolar hemorrhage (AH) is characterized by the acute onset of alveolar bleeding and hypoxemia and can be fatal. Thrombin has been widely used to achieve coagulation and hemostasis. However, the efficacy of thrombin in patients with AH is unclear. Thus, this study aimed to evaluate the efficacy of thrombin administration in patients with hematological malignancy and AH. PATIENT CONCERNS AND DIAGNOSES: This retrospective study included 15 hematological malignancy patients (8 men and 7 women; mean age 47.7 ±â€Š17.3 years) with AH who were administered intrapulmonary thrombin between March 2013 and July 2018. INTERVENTIONS AND OUTCOMES: All patients received bovine-origin thrombin (1000 IU/ml, Reyon Pharmaceutical Co., Ltd., Seoul, Korea) via a fiberoptic bronchoscope. A maximum of 15 ml of thrombin was injected via the working channel to control bleeding. The ability of thrombin to control bleeding was assessed. Additionally, the change in the PaO2/FiO2 (PF) ratio after intrapulmonary thrombin administration was evaluated. Intrapulmonary thrombin was administered a minimum of 3 days after starting mechanical ventilation in all patients, and it immediately controlled the active bleeding in 13 of 15 patients (86.7%). However, AH relapse was noted in 3 of the 13 patients (23.1%). The PF ratio improved in 10 of 15 patients (66.6%), and the mean PF ratio was significantly higher after thrombin administration than before administration (P = .03). No adverse thromboembolic complications or systemic adverse events were observed. CONCLUSION: Thrombin administration was effective in controlling bleeding in hematological malignancy patients with AH. Intrapulmonary thrombin administration might be a good therapeutic option for treating AH.


Assuntos
Neoplasias Hematológicas/complicações , Hemorragia/tratamento farmacológico , Hemostáticos/uso terapêutico , Pneumopatias/tratamento farmacológico , Trombina/uso terapêutico , Adolescente , Adulto , Idoso , Feminino , Hemorragia/etiologia , Hemostáticos/administração & dosagem , Humanos , Pneumopatias/etiologia , Masculino , Pessoa de Meia-Idade , Alvéolos Pulmonares/patologia , Estudos Retrospectivos , Trombina/administração & dosagem , Adulto Jovem
17.
Leuk Res ; 94: 106356, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32445941

RESUMO

Hemorrhagic death is the leading cause of treatment failure in acute promyelocytic leukemia (APL). Our ability to identify patients at greatest risk of hemorrhage, and to actively prevent hemorrhage, remains limited. Nevertheless, some data is available to guide contemporary clinical practice and future investigation. Circulating disease burden, best represented by the peripheral WBC / blast count, is the most consistent predictor of major and fatal bleeding risk. In contrast, laboratory markers of disseminated intravascular coagulation (DIC) appear to be poor predictors. A number of interventions have been posited to reduce bleeding risk. Prompt initiation of all-trans retinoic acid (ATRA), avoidance of invasive procedures, transfusion support, and cytoreduction all have theoretical merit. Though they lack strong evidence to support their benefit with respect to bleeding, they are associated with limited risks, and are therefore advisable. Low-dose therapeutic heparin and antifibrinolytics have not shown the ability to positively modify bleeding risk, and heparin has been associated with harm. Thrombomodulin has shown promise in limited retrospective studies however further prospective data are needed. rFVIIa may have a role in cases of life-threatening bleeding however evidence is largely anecdotal. Additional studies evaluating the above interventions, and investigating other potential interventions are needed.


Assuntos
Crise Blástica , Hemorragia , Leucemia Promielocítica Aguda , Crise Blástica/sangue , Crise Blástica/complicações , Crise Blástica/tratamento farmacológico , Crise Blástica/patologia , Fator VIII/uso terapêutico , Hemorragia/sangue , Hemorragia/tratamento farmacológico , Hemorragia/etiologia , Hemorragia/patologia , Heparina/uso terapêutico , Humanos , Leucemia Promielocítica Aguda/sangue , Leucemia Promielocítica Aguda/complicações , Leucemia Promielocítica Aguda/tratamento farmacológico , Leucemia Promielocítica Aguda/patologia , Trombomodulina/uso terapêutico , Tretinoína/uso terapêutico
18.
PLoS One ; 15(5): e0233640, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32453766

RESUMO

Understanding the coagulation process is critical to developing treatments for trauma and coagulopathies. Clinical studies on tranexamic acid (TXA) have resulted in mixed reports on its efficacy in improving outcomes in trauma patients. The largest study, CRASH-2, reported that TXA improved outcomes in patients who received treatment prior to 3 hours after the injury, but worsened outcomes in patients who received treatment after 3 hours. No consensus has been reached about the mechanism behind the duality of these results. In this paper we use a computational model for coagulation and fibrinolysis to propose that deficiencies or depletions of key anti-fibrinolytic proteins, specifically antiplasmin, a1-antitrypsin and a2-macroglobulin, can lead to worsened outcomes through urokinase-mediated hyperfibrinolysis.


Assuntos
Transtornos da Coagulação Sanguínea/tratamento farmacológico , Ácido Tranexâmico/uso terapêutico , Ativador de Plasminogênio Tipo Uroquinase/genética , Ferimentos e Lesões/tratamento farmacológico , Antifibrinolíticos/uso terapêutico , Coagulação Sanguínea/genética , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/genética , Transtornos da Coagulação Sanguínea/patologia , Simulação por Computador , Fibrina/genética , Tempo de Lise do Coágulo de Fibrina , Fibrinolisina/genética , Fibrinólise/efeitos dos fármacos , Hemorragia/sangue , Hemorragia/tratamento farmacológico , Hemorragia/genética , Humanos , Proteínas de Membrana/genética , Mortalidade , alfa 2-Macroglobulinas Associadas à Gravidez/genética , Trombina/genética , Trombina/metabolismo , Ferimentos e Lesões/sangue , Ferimentos e Lesões/genética , Ferimentos e Lesões/patologia , alfa 1-Antitripsina/genética
19.
Medicine (Baltimore) ; 99(16): e19720, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32311960

RESUMO

BACKGROUND: Hemorrhoidal disease (HD) is one of the commonest proctologic condition in the general population. Medical therapy for HD has not been formally confirmed due to the inconsistent of results. Liang-Xue-Di-Huang Decoction, a kind of ancient Chinese classical prescription, has been used to treat HD from the 19th century in China. However, clinical research of Liang-Xue-Di-Huang Decoction in the treatment of HD was lack. We designed this study to evaluate the efficacy and safety of Liang-Xue-Di-Huang Decoction in the treatment of HD. METHODS/DESIGN: A randomized, controlled, double blind, double-mimetic agent, and multicenter trial to evaluate the efficacy and safety of Liang-Xue-Di-Huang Decoction is proposed. HD patients (stage I, II, III) will be randomly assigned into experimental group or control group. HD patients will receive a 7-day treatments and a 7-day follow-up. The primary outcome measure is the Hemorrhoid Bleeding Score in 7 and 14 days. The Secondary outcome measures are Goligher prolapse score and quality-of-life score in 7 and 14 days. DISCUSSION: This study will provide objective evidences to evaluate the efficacy and safety of Liang-Xue-Di-Huang Decoction in treatment of HD.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Hemorragia/tratamento farmacológico , Hemorroidas/tratamento farmacológico , Hemorragia/etiologia , Hemorroidas/complicações , Humanos , Medicina Tradicional Chinesa , Fitoterapia
20.
Am J Case Rep ; 21: e919536, 2020 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-32249274

RESUMO

BACKGROUND Thrombocytopenia, anasarca, fever, reticulin fibrosis/renal failure, and organomegaly (TAFRO) syndrome is a variant of idiopathic multicentric Castleman disease. Adrenal hemorrhage has rarely been reported in TAFRO syndrome, and previous cases have mainly been Asian patients. This report is of two Caucasian patients with TAFRO syndrome presenting with acute adrenal insufficiency due to bilateral adrenal hemorrhage. CASE REPORT Case 1 was a 19-year-old Caucasian man with no significant past medical history who was admitted with acute abdominal pain, vomiting, anorexia, and moderate weight loss. Case 2 was a 31-year-old Caucasian woman with no past medical history who was admitted to hospital with fever, dyspnea, thoracic and abdominal pain, polyarthralgia, and hypotension. Both patients had splenomegaly, mild lymphadenopathy, thrombocytopenia, acute kidney injury, and myelofibrosis. In both cases, lymph node biopsy histology showed mixed-type idiopathic multicentric Castleman disease. In both patients, a diagnosis of TAFRO was made, and they developed bilateral adrenal hemorrhage with adrenal insufficiency. Case 1 was treated with high-dose steroids, followed by tocilizumab infusion. Due to persistent thrombocytopenia, second-line treatment commenced with rituximab, but the patient relapsed two months later. Tocilizumab treatment was recommenced, which was followed by an immuno-allergic adverse event. He then had a good response to sirolimus. Case 2 died nine months after diagnosis due to acute respiratory distress. CONCLUSIONS Two cases of TAFRO syndrome presented with acute adrenal insufficiency due to bilateral adrenal hemorrhage. The symptoms were only partially controlled with tocilizumab, rituximab, and tacrolimus. Adrenal hemorrhage may be a specific manifestation of TAFRO syndrome.


Assuntos
Doenças das Glândulas Suprarrenais/tratamento farmacológico , Hiperplasia do Linfonodo Gigante/tratamento farmacológico , Hemorragia/tratamento farmacológico , Evolução Fatal , Feminino , Humanos , Masculino , Adulto Jovem
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