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1.
N Engl J Med ; 385(9): 790-802, 2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34351721

RESUMO

BACKGROUND: Thrombosis and inflammation may contribute to the risk of death and complications among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation may improve outcomes in noncritically ill patients who are hospitalized with Covid-19. METHODS: In this open-label, adaptive, multiplatform, controlled trial, we randomly assigned patients who were hospitalized with Covid-19 and who were not critically ill (which was defined as an absence of critical care-level organ support at enrollment) to receive pragmatically defined regimens of either therapeutic-dose anticoagulation with heparin or usual-care pharmacologic thromboprophylaxis. The primary outcome was organ support-free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge. This outcome was evaluated with the use of a Bayesian statistical model for all patients and according to the baseline d-dimer level. RESULTS: The trial was stopped when prespecified criteria for the superiority of therapeutic-dose anticoagulation were met. Among 2219 patients in the final analysis, the probability that therapeutic-dose anticoagulation increased organ support-free days as compared with usual-care thromboprophylaxis was 98.6% (adjusted odds ratio, 1.27; 95% credible interval, 1.03 to 1.58). The adjusted absolute between-group difference in survival until hospital discharge without organ support favoring therapeutic-dose anticoagulation was 4.0 percentage points (95% credible interval, 0.5 to 7.2). The final probability of the superiority of therapeutic-dose anticoagulation over usual-care thromboprophylaxis was 97.3% in the high d-dimer cohort, 92.9% in the low d-dimer cohort, and 97.3% in the unknown d-dimer cohort. Major bleeding occurred in 1.9% of the patients receiving therapeutic-dose anticoagulation and in 0.9% of those receiving thromboprophylaxis. CONCLUSIONS: In noncritically ill patients with Covid-19, an initial strategy of therapeutic-dose anticoagulation with heparin increased the probability of survival to hospital discharge with reduced use of cardiovascular or respiratory organ support as compared with usual-care thromboprophylaxis. (ATTACC, ACTIV-4a, and REMAP-CAP ClinicalTrials.gov numbers, NCT04372589, NCT04505774, NCT04359277, and NCT02735707.).


Assuntos
Anticoagulantes/administração & dosagem , COVID-19/tratamento farmacológico , Heparina/administração & dosagem , Trombose/prevenção & controle , Adulto , Idoso , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , COVID-19/mortalidade , Feminino , Hemorragia/induzido quimicamente , Heparina/efeitos adversos , Heparina/uso terapêutico , Heparina de Baixo Peso Molecular/uso terapêutico , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida
2.
N Engl J Med ; 385(9): 777-789, 2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34351722

RESUMO

BACKGROUND: Thrombosis and inflammation may contribute to morbidity and mortality among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation would improve outcomes in critically ill patients with Covid-19. METHODS: In an open-label, adaptive, multiplatform, randomized clinical trial, critically ill patients with severe Covid-19 were randomly assigned to a pragmatically defined regimen of either therapeutic-dose anticoagulation with heparin or pharmacologic thromboprophylaxis in accordance with local usual care. The primary outcome was organ support-free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge. RESULTS: The trial was stopped when the prespecified criterion for futility was met for therapeutic-dose anticoagulation. Data on the primary outcome were available for 1098 patients (534 assigned to therapeutic-dose anticoagulation and 564 assigned to usual-care thromboprophylaxis). The median value for organ support-free days was 1 (interquartile range, -1 to 16) among the patients assigned to therapeutic-dose anticoagulation and was 4 (interquartile range, -1 to 16) among the patients assigned to usual-care thromboprophylaxis (adjusted proportional odds ratio, 0.83; 95% credible interval, 0.67 to 1.03; posterior probability of futility [defined as an odds ratio <1.2], 99.9%). The percentage of patients who survived to hospital discharge was similar in the two groups (62.7% and 64.5%, respectively; adjusted odds ratio, 0.84; 95% credible interval, 0.64 to 1.11). Major bleeding occurred in 3.8% of the patients assigned to therapeutic-dose anticoagulation and in 2.3% of those assigned to usual-care pharmacologic thromboprophylaxis. CONCLUSIONS: In critically ill patients with Covid-19, an initial strategy of therapeutic-dose anticoagulation with heparin did not result in a greater probability of survival to hospital discharge or a greater number of days free of cardiovascular or respiratory organ support than did usual-care pharmacologic thromboprophylaxis. (REMAP-CAP, ACTIV-4a, and ATTACC ClinicalTrials.gov numbers, NCT02735707, NCT04505774, NCT04359277, and NCT04372589.).


Assuntos
Anticoagulantes/administração & dosagem , COVID-19/tratamento farmacológico , Heparina/administração & dosagem , Trombose/prevenção & controle , Idoso , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , COVID-19/mortalidade , Estado Terminal , Feminino , Hemorragia/induzido quimicamente , Heparina/efeitos adversos , Heparina/uso terapêutico , Mortalidade Hospitalar , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Respiração Artificial , Falha de Tratamento
4.
Biochem Med (Zagreb) ; 31(2): 021003, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34140837

RESUMO

This case report describes false shortening of activated partial thromboplastin time (aPTT) due to erroneous optical reading of the clotting point in the presence of unfractionated heparin (UFH), and a biphasic waveform. Activated partial thromboplastin time performed on a coagulometer with photo-optical detection yielded an ambiguous clotting curve characterized by an early and steady decrease in light transmittance throughout the whole measuring range, with the clotting point read at 65 seconds. Further investigations included measurement of aPTT by means of a mechanical clot detection method as well as determination of another heparin-sensitive coagulation assay, that is thrombin time (TT), both being unmeasurably prolonged (> 150 seconds). Communication with clinicians revealed that the patient was on continuous UFH therapy and had an underlying sepsis, with highly elevated C-reactive protein (289 mg/L). The aPTT measurements requested at three timepoints later during the same day revealed gradual aPTT shortening and unveiled a peculiar biphasic waveform pattern. In this case, unmeasurably prolonged aPTT due to UFH therapy was masked by a biphasic aPTT curve pattern making only the first slope of the biphasic waveform visible within the measuring range. The early decrease in plasma light transmittance mimicked optical changes related to clot formation, thus causing erroneous optical reading and yielding a falsely shortened aPTT. This case emphasizes that such a pattern should be carefully inspected, especially when a combination of a critically ill condition and UFH therapy is present, in order to prevent erroneous reporting of aPTT and potential adverse effects on patient care.


Assuntos
Anticoagulantes/administração & dosagem , Proteína C-Reativa/metabolismo , Heparina/administração & dosagem , Sepse/sangue , Sepse/tratamento farmacológico , Anticoagulantes/farmacocinética , Heparina/farmacocinética , Humanos , Masculino , Tempo de Tromboplastina Parcial
5.
Medicine (Baltimore) ; 100(23): e26313, 2021 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-34115042

RESUMO

RATIONALE: In coronavirus disease 2019 (COVID-19) patients with acute respiratory distress syndrome refractory to optimal conventional management, we should consider the indication for veno-venous extracorporeal membrane oxygenation (V-V ECMO). Growing evidence indicates that COVID-19 frequently causes coagulopathy, presenting as hypercoagulation and incidental thrombosis. For these reasons, a multifactorial approach with several anticoagulant markers should be considered in the management of anticoagulation using heparin in COVID-19 patients on V-V ECMO. PATIENT CONCERNS: A 48-year-old man was infected with COVID-19 with a worsening condition manifesting as acute respiratory distress syndrome. DIAGNOSES: He was refractory to conventional therapy, thus we decided to introduce V-V ECMO. We used heparin as an anticoagulant therapy for V-V ECMO and adjusted the doses of heparin by careful monitoring of the activated clotting time (ACT) and activated partial thromboplastin time (APTT) to avoid both hemorrhagic and thrombotic complications. We controlled the doses of heparin in the therapeutic ranges of ACT and APTT, but clinical hemorrhaging and profound elevation of coagulant marker became apparent. INTERVENTIONS: Using thromboelastography (TEG; Haemonetics) in addition to ACT and APTT, we were able to clearly detect not only sufficient coagulability of COVID19 on V-V ECMO (citrated rapid thromboelastography-R 0.5 min, angle 75.5°, MA 64.0 mm, citrated functional fibrinogen-MA 20.7 mm) but also an excessive effect of heparin (citrated kaolin -R 42.7 min, citrated kaolin with heparinase 11.7 min). OUTCOMES: Given the TEG findings indicating an excessive heparin effect, the early withdrawal of ECMO was considered. After an evaluation of the patient's respiratory capacity, withdrawal from V-V ECMO was achieved and then anticoagulation was stopped. The hemorrhagic complications and elevated thrombotic marker levels dramatically decreased. LESSONS: TEG monitoring might be a useful option for managing anticoagulation in COVID-19 patients on V-V ECMO frequently showing a hypercoagulative state and requiring massive doses of heparin, to reduce both hemorrhagic and thrombotic complications.


Assuntos
Anticoagulantes/administração & dosagem , COVID-19/complicações , Oxigenação por Membrana Extracorpórea , Heparina/administração & dosagem , Síndrome do Desconforto Respiratório/terapia , Tromboelastografia , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome do Desconforto Respiratório/virologia
6.
Plast Reconstr Surg ; 148(1): 14e-18e, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34003808

RESUMO

SUMMARY: Autologous breast reconstruction has evolved considerably from pedicled muscle-based approaches to microsurgical perforator-based techniques. Patients with documented coagulopathy, however, remain a particularly challenging population. The authors present their experience in microsurgical breast reconstruction in patients with coagulopathy and discuss their treatment protocol. A prospectively maintained database was queried for patients with coagulopathy who underwent microsurgical breast reconstruction between 2016 and 2019. Information regarding patient demographics, type of coagulopathy, and anticoagulation regimen were retrieved, and clinical outcomes were investigated. Nineteen patients who underwent 34 microsurgical breast reconstructions with free abdominal flaps were included in the study. The most common coagulopathy was factor V Leiden [n = 7 (38.6 percent)]. Nine patients (47.4 percent) developed thrombotic complications (the majority occurring intraoperatively); notably, arterial and venous thrombosis in four (21.1 percent) and two patients (10.5 percent), respectively. Postoperative thrombotic complications included pulmonary embolism [n = 2 (10.5 percent)] and flap congestion secondary to venous thrombosis [two flaps (5.9 percent)]. Only one flap loss was observed secondary to delayed venous thrombosis on postoperative day 6 (2.9 percent). The anticoagulation regimen in the majority of patients consisted of intraoperative intravenous administration of heparin (2000 U [bolus]) followed by a 5-day heparin infusion at 500 U/hour [n = 10 (52.6 percent)]. The high rate of thrombotic complications in patients with coagulopathy who underwent microsurgical breast reconstruction is contrasted by a low flap loss rate. Although coagulopathy is a risk factor for thrombotic complications, successful microsurgical breast reconstruction is still possible in the majority of patients.


Assuntos
Transtornos da Coagulação Sanguínea/complicações , Neoplasias da Mama/cirurgia , Mamoplastia/efeitos adversos , Microcirurgia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Trombose/epidemiologia , Administração Intravenosa , Adulto , Anticoagulantes/administração & dosagem , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/tratamento farmacológico , Transtornos da Coagulação Sanguínea/epidemiologia , Neoplasias da Mama/complicações , Feminino , Retalhos de Tecido Biológico/transplante , Sobrevivência de Enxerto , Heparina/administração & dosagem , Humanos , Mamoplastia/métodos , Microcirurgia/métodos , Pessoa de Meia-Idade , Retalho Perfurante/transplante , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco , Trombose/sangue , Trombose/etiologia , Trombose/prevenção & controle , Transplante Autólogo/efeitos adversos , Transplante Autólogo/métodos , Resultado do Tratamento
8.
CMAJ Open ; 9(2): E585-E591, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34021017

RESUMO

BACKGROUND: We identified the need to modernize frostbite management in our northern centre and implemented a treatment protocol in 2015. Our aim was to describe the clinical course of patients presenting to the hospital since the implementation of the protocol. METHODS: This was a retrospective case series from Whitehorse General Hospital, Whitehorse, Yukon Territory, Canada. We reviewed the charts of patients who presented to the hospital with grade 2-4 frostbite and were treated as per our protocol between Feb. 9, 2015, and Feb. 8, 2020. Patients with grade 2-4 frostbite received iloprost; in addition, those with grade 4 frostbite received alteplase and heparin. We determined the number of digits affected and salvaged, and the time from presentation to the emergency department to treatment initiation. We also examined patients' demographic characteristics, predisposing events, frostbite severity and adverse drug reactions. RESULTS: In 22 patients treated for grade 2-4 frostbite, 142 digits were affected: 59 with grade 2 frostbite, 25 with grade 3 frostbite and 58 with grade 4 frostbite; of the 142, 113 (79.6%) were salvaged. All 29 digits amputated had grade 4 frostbite. The mean time from presentation to iloprost initiation was reduced from 32.9 hours in 2015 to 3.0 hours in 2020. Sports (10 cases [45%]) and alcohol use (6 [27%]) were the most common precipitating events, with alcohol use tending to result in more severe injury (grade 4 in 5 of 6 cases). Adverse reactions with iloprost (e.g., headache) were common but mild. Adverse reactions with alteplase (e.g., bleeding) were less common but of greater clinical significance. INTERPRETATION: Over the study period, our protocol contributed to improvement in frostbite care at our institution, resulting in a digit salvage rate comparable to other published results. Our 5-year experience shows that advanced medical care of frostbite can be achieved, even at a rural centre.


Assuntos
Amputação , Dedos , Congelamento das Extremidades , Heparina , Iloprosta , Ativador de Plasminogênio Tecidual , Adulto , Consumo de Bebidas Alcoólicas/epidemiologia , Amputação/métodos , Amputação/estatística & dados numéricos , Serviços Médicos de Emergência/métodos , Feminino , Fibrinolíticos/administração & dosagem , Fibrinolíticos/efeitos adversos , Dedos/patologia , Dedos/cirurgia , Congelamento das Extremidades/diagnóstico , Congelamento das Extremidades/epidemiologia , Congelamento das Extremidades/cirurgia , Congelamento das Extremidades/terapia , Heparina/administração & dosagem , Heparina/efeitos adversos , Humanos , Iloprosta/administração & dosagem , Iloprosta/efeitos adversos , Masculino , Avaliação de Processos e Resultados em Cuidados de Saúde , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Esportes/estatística & dados numéricos , Tempo para o Tratamento/normas , Ativador de Plasminogênio Tecidual/administração & dosagem , Ativador de Plasminogênio Tecidual/efeitos adversos , Vasodilatadores/administração & dosagem , Vasodilatadores/efeitos adversos , Yukon/epidemiologia
9.
Int J Mol Sci ; 22(8)2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33920853

RESUMO

A self-nanoemulsifying drug delivery system (SNEDDS) was developed to enhance the absorption of heparin after oral administration, in which heparin was compounded with phospholipids to achieve better fat solubility in the form of heparin-phospholipid (HEP-Pc) complex. HEP-Pc complex was prepared using the solvent evaporation method, which increased the solubility of heparin in n-octanol. The successful preparation of HEP-Pc complex was confirmed by differential scanning calorimetry (DSC), Fourier-transform infrared (FT-IR) spectroscopy, NMR, and SEM. A heparin lipid microemulsion (HEP-LM) was prepared by high-pressure homogenization and characterized. HEP-LM can enhance the absorption of heparin after oral administration, significantly prolong activated partial thromboplastin time (APTT) and thrombin time (TT) in mice, and reduce fibrinogen (FIB) content. All these outcomes indicate that HEP-LM has great potential as an oral heparin formulation.


Assuntos
Sistemas de Liberação de Medicamentos , Emulsões/química , Heparina/farmacologia , Nanopartículas/química , Fosfolipídeos/química , Administração Oral , Animais , Anticoagulantes/farmacologia , Varredura Diferencial de Calorimetria , Heparina/administração & dosagem , Masculino , Camundongos , Nanopartículas/ultraestrutura , Tamanho da Partícula , Espectroscopia de Prótons por Ressonância Magnética , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier
10.
Front Immunol ; 12: 613070, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33815368

RESUMO

Lack of specific antiviral treatment for COVID-19 has resulted in long hospitalizations and high mortality rate. By harnessing the regulatory effects of adenosine on inflammatory mediators, we have instituted a new therapeutic treatment with inhaled adenosine in COVID-19 patients, with the aim of reducing inflammation, the onset of cytokine storm, and therefore to improve prognosis. The use of inhaled adenosine in COVID19 patients has allowed reduction of length of stay, on average 6 days. This result is strengthened by the decrease in SARS-CoV-2 positive days. In treated patients compared to control, a clear improvement in PaO2/FiO2 was observed together with a reduction in inflammation parameters, such as the decrease of CRP level. Furthermore, the efficacy of inhaled exogenous adenosine led to an improvement of the prognosis indices, NLR and PLR. The treatment seems to be safe and modulates the immune system, allowing an effective response against the viral infection progression, reducing length of stay and inflammation parameters.


Assuntos
Adenosina/farmacologia , COVID-19/tratamento farmacológico , Adenosina/uso terapêutico , Adulto , Idoso , Antibacterianos/administração & dosagem , Azitromicina/administração & dosagem , COVID-19/diagnóstico por imagem , COVID-19/fisiopatologia , Estudos de Casos e Controles , Inibidores do Citocromo P-450 CYP3A/administração & dosagem , Síndrome da Liberação de Citocina/fisiopatologia , Inibidores Enzimáticos/administração & dosagem , Feminino , Heparina/administração & dosagem , Hospitalização , Humanos , Hidroxicloroquina/administração & dosagem , Inflamação/tratamento farmacológico , Lopinavir/administração & dosagem , Masculino , Pessoa de Meia-Idade , Prognóstico , Tomografia Computadorizada por Raios X
12.
ASAIO J ; 67(4): 411-415, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33769995

RESUMO

The preferred assay for measuring and adjusting unfractionated heparin (UFH) infusion to achieve optimal outcomes during extracorporeal membrane oxygenation (ECMO) is not well established. This retrospective cohort study explored safety and efficacy outcome differences between anti-factor Xa (anti-Xa) and activated partial thromboplastin time (aPTT) for UFH in adult venoarterial ECMO. Forty-one patients were included and analyzed. The UFH rate at first goal and time to goal were both higher in the aPTT versus anti-Xa cohort but did not achieve statistical significance (12.14 vs. 9.58 unit/kg/hour (p = 0.29), 20.22 vs. 12.05 hours (p = 0.11)). The aPTT cohort was in target goals 35.0% of the time versus 47.7% in the anti-Xa cohort (p = 0.13), above goal 41.0% vs. 17.3% (p = 0.02), and below-goal 24.0% versus 35.0% of the time (p = 0.34). Minimum heparin rates in the aPTT cohort were 6.28 vs. 3.33 unit/kg/hour in the anti-Xa cohort (p = 0.07), and the maximum UFH rate was 18.77 unit/kg/hour vs. 15.48 unit/kg/hour (p = 0.10). Our findings suggest that aPTT monitoring may result in a delay to target attainment, higher UFH rates, and overall exposure.


Assuntos
Anticoagulantes/administração & dosagem , Oxigenação por Membrana Extracorpórea , Inibidores do Fator Xa/sangue , Heparina/administração & dosagem , Tempo de Tromboplastina Parcial , Adulto , Coagulação Sanguínea/efeitos dos fármacos , Estudos de Coortes , Monitoramento de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
13.
BMC Pulm Med ; 21(1): 102, 2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33761886

RESUMO

BACKGROUND: Coronavirus Disease 2019 (COVID-19) is a pandemic affecting all countries in the world. Italy has been particularly afflicted by the health emergency, and since the peak phase has passed, major concern regarding medium to long term complications due to COVID-19 is arising. Little is known in literature regarding thromboembolic complications once healed after COVID-19. CASE PRESENTATION: A 51-year-old patient recovered from COVID-19 pneumonia complicated by pulmonary embolism (PE) came to the hospital for palpitations and chest pain. Although he was on treatment dose of direct oral anticoagulation (DOAC), massive recurrent PE was diagnosed. CONCLUSION: In the early post COVID-19 era, the question remains regarding the efficacy of DOACs in COVID-19 patients.


Assuntos
Anticoagulantes/administração & dosagem , COVID-19/complicações , Dabigatrana/administração & dosagem , Heparina/administração & dosagem , Embolia Pulmonar/prevenção & controle , Embolia Pulmonar/virologia , Varfarina/administração & dosagem , Administração Oral , Anticoagulantes/uso terapêutico , Dabigatrana/uso terapêutico , Quimioterapia Combinada , Heparina/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Embolia Pulmonar/tratamento farmacológico , Recidiva , Varfarina/uso terapêutico
14.
BMJ Case Rep ; 14(3)2021 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-33753396

RESUMO

Coagulation predominant-type coagulopathy such as microthrombosis and macrothrombosis is a well-known recognised complication found in COVID-19 infected critically ill patients. In the context of high incidence of thrombotic events in patients with COVID-19, supplementation with anticoagulant therapy has been routinely recommended and shown to reduce mortality. However, the recommended type, dose, duration and timing of anticoagulant has not been determined yet. Spontaneous retroperitoneal haematoma secondary to anticoagulant therapy is one of the well-known but self-limiting conditions. We report a 51-year-old COVID-19 positive woman, who was taking intermediate-intensity heparin therapy for venous thromboembolism prophylaxis and died from complication of retroperitoneal bleeding. Further studies are needed to verify the risk-benefit ratio of anticoagulant therapy in patients with COVID-19. Although anticoagulant deems appropriate to use in patients with COVID-19, clinicians should be cautious about major bleeding complication such as retroperitoneal haemorrhage even when full therapeutic dosage is not used.


Assuntos
Anticoagulantes/efeitos adversos , COVID-19/tratamento farmacológico , Hemorragia/induzido quimicamente , Heparina/efeitos adversos , Espaço Retroperitoneal , Anticoagulantes/administração & dosagem , Anticoagulantes/uso terapêutico , COVID-19/complicações , COVID-19/diagnóstico por imagem , Esquema de Medicação , Evolução Fatal , Feminino , Heparina/administração & dosagem , Heparina/uso terapêutico , Humanos , Pessoa de Meia-Idade , Radiografia , SARS-CoV-2 , Tomografia Computadorizada por Raios X , Tromboembolia Venosa/prevenção & controle
16.
Medicine (Baltimore) ; 100(7): e24695, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33607810

RESUMO

RATIONALE: Cisplatin is one of the key drugs that is frequently used for treating various types of malignancies. Although renal and digestive toxicities are well-known cisplatin-related toxicities, attention should also be paid to acute aortic thrombosis, a relatively rare but potentially fatal disorder caused by cisplatin. Additionally, D-dimer is mainly measured to detect venous thromboembolism or disseminated intravascular coagulation, whereas its usefulness for detecting aortic thrombosis remains unclear. Here, we report a case of squamous cell lung cancer treated with cisplatin-based chemotherapy, wherein acute aortic thrombosis was diagnosed based on elevated D-dimer levels. PATIENT CONCERNS: A 65-year-old man with stage IV squamous cell lung cancer presented with elevated D-dimer levels during treatment with second-line chemotherapy with cisplatin and S-1. Contrast-enhanced computed tomography (CT) revealed an intramural thrombus, which had not been previously identified, extending from the abdominal aorta to the common iliac artery. DIAGNOSES: We diagnosed the patient as having acute aortic thrombosis caused by cisplatin. INTERVENTIONS: The patient received intravenous administration of unfractionated heparin for 9 days followed by oral warfarin. OUTCOMES: One month after initiating treatment, the patient's D-dimer levels decreased to the normal range, and contrast-enhanced CT revealed that the thrombi had nearly completely disappeared without any sequelae or organ damage. LESSONS: Our findings revealed that cisplatin can cause acute aortic thrombosis and that regular measurements of D-dimer levels before and during chemotherapy may contribute to the early detection of acute aortic thrombosis.


Assuntos
Doenças da Aorta/patologia , Cisplatino/toxicidade , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Trombose/induzido quimicamente , Administração Intravenosa , Administração Oral , Idoso , Anticoagulantes/administração & dosagem , Anticoagulantes/uso terapêutico , Antineoplásicos/toxicidade , Carcinoma de Células Escamosas/tratamento farmacológico , Produtos de Degradação da Fibrina e do Fibrinogênio/efeitos dos fármacos , Heparina/administração & dosagem , Heparina/uso terapêutico , Humanos , Neoplasias Pulmonares/patologia , Masculino , Estadiamento de Neoplasias/métodos , Trombose/diagnóstico por imagem , Trombose/tratamento farmacológico , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento , Varfarina/administração & dosagem , Varfarina/uso terapêutico
18.
Pan Afr Med J ; 38: 9, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33520078

RESUMO

In this paper, we report two cases of induced thrombocytopenia after the infusion of glycoprotein (GP) IIb/IIIa receptors antagonists, following a coronary angioplasty. The first patient is a 65-year-old woman, admitted with acute coronary syndrome requiring percutaneous angioplasty with stenting. The patient was given tirofiban + unfractionated heparin (UFH). Ten hours later, the patient revealed very severe thrombocytopenia and went into hemorrhagic shock (hematemesis and hematoma at the injection site). The patient was transfused with nine units of red blood cells (RBCs), 24 platelets pellets and 4 units of fresh frozen plasma (FFP). The second patient is a 76-year-old woman. She was admitted to hospital for acute coronary syndrome necessitating percutaneous angioplasty with stenting and a glycoprotein IIb/IIIa receptor antagonists, tirofiban + unfractionated (UFH). Four hours later, the patient presented with gingivorrhagia associated thrombocytopenia. She received six platelet pellets transfusion with well clinical and biological improvement. These two observations raise the significance of a close monitoring of platelet count after the initiation of GP IIb/IIIa antagonists infusion, which are sometimes responsible for life-threatening adverse events.


Assuntos
Inibidores da Agregação Plaquetária/efeitos adversos , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/antagonistas & inibidores , Trombocitopenia/induzido quimicamente , Tirofibana/efeitos adversos , Idoso , Angioplastia Coronária com Balão , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Feminino , Heparina/administração & dosagem , Heparina/efeitos adversos , Humanos , Plasma , Inibidores da Agregação Plaquetária/administração & dosagem , Transfusão de Plaquetas , Trombocitopenia/terapia , Tirofibana/administração & dosagem
19.
BMJ Case Rep ; 14(2)2021 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-33563670

RESUMO

Cerebral vasculitis is a serious complication of bacterial meningitis that can cause significant morbidity and mortality due to stroke. Currently, there are no treatment guidelines or safety and efficacy studies on the management of cerebral vasculitis in this context. Herein, we report a case of a previously well 11-year-old girl who presented with acute otitis media that progressed to mastoiditis and fulminant meningitis. Group A Streptococcus was found in blood and ear-fluid cultures (lumbar puncture was unsuccessful). Her decreased level of consciousness persisted despite appropriate antimicrobial treatment, and repeat MRI revealed extensive large vessel cerebral vasculitis. Based on expert opinion and a presumed inflammatory mechanism, her cerebral vasculitis was treated with 7 days of pulse intravenous methylprednisolone followed by oral prednisone taper. She was also treated with intravenous heparin. Following these therapies, she improved clinically and radiographically with no adverse events. She continues to undergo rehabilitation with improvement.


Assuntos
Antibacterianos/administração & dosagem , Heparina/administração & dosagem , Meningites Bacterianas/diagnóstico , Meningites Bacterianas/tratamento farmacológico , Infecções Estreptocócicas/diagnóstico , Infecções Estreptocócicas/tratamento farmacológico , Vasculite do Sistema Nervoso Central/diagnóstico , Vasculite do Sistema Nervoso Central/tratamento farmacológico , Criança , Diagnóstico Diferencial , Diagnóstico por Imagem , Quimioterapia Combinada , Feminino , Humanos , Meningites Bacterianas/microbiologia , Infecções Estreptocócicas/microbiologia , Streptococcus pyogenes , Vasculite do Sistema Nervoso Central/microbiologia
20.
Lancet Respir Med ; 9(4): 360-372, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33493448

RESUMO

BACKGROUND: Mechanical ventilation in intensive care for 48 h or longer is associated with the acute respiratory distress syndrome (ARDS), which might be present at the time ventilatory support is instituted or develop afterwards, predominantly during the first 5 days. Survivors of prolonged mechanical ventilation and ARDS are at risk of considerably impaired physical function that can persist for years. An early pathogenic mechanism of lung injury in mechanically ventilated, critically ill patients is inflammation-induced pulmonary fibrin deposition, leading to thrombosis of the microvasculature and hyaline membrane formation in the air sacs. The main aim of this study was to determine if nebulised heparin, which targets fibrin deposition, would limit lung injury and thereby accelerate recovery of physical function in patients with or at risk of ARDS. METHODS: The Can Heparin Administration Reduce Lung Injury (CHARLI) study was an investigator-initiated, multicentre, double-blind, randomised phase 3 trial across nine hospitals in Australia. Adult intensive care patients on invasive ventilation, with impaired oxygenation defined by a PaO2/FiO2 ratio of less than 300, and with the expectation of invasive ventilation beyond the next calendar day were recruited. Key exclusion criteria were heparin allergy, pulmonary bleeding, and platelet count less than 50 X 109/L. Patients were randomly assigned 1:1, with stratification by site and using blocks of variable size and random seed, via a web-based system, to either unfractionated heparin sodium 25 000 IU in 5 mL or identical placebo (sodium chloride 0·9% 5 mL), administered using a vibrating mesh membrane nebuliser every 6 h to day 10 while invasively ventilated. Patients, clinicians, and investigators were masked to treatment allocation. The primary outcome was the Short Form 36 Health Survey Physical Function Score (out of 100) of survivors at day 60. Prespecified secondary outcomes, which are exploratory, included development of ARDS to day 5 among at-risk patients, deterioration of the Murray Lung Injury Score (MLIS) to day 5, mortality at day 60, residence of survivors at day 60, and serious adverse events. Analyses followed the intention-to-treat principle. There was no imputation of missing data. The trial is registered with the Australian and New Zealand Clinical Trials Register, number ACTRN12612000418875 . FINDINGS: Between Sept 4, 2012, and Aug 23, 2018, 256 patients were randomised. Final follow-up was on Feb 25, 2019. We excluded three patients who revoked consent and one ineligible participant who received no intervention. Of 252 patients included in data analysis, the mean age was 58 years (SD 15), 157 (62%) were men, and 118 (47%) had ARDS. 128 (51%) patients were assigned to the heparin group and 124 (49%) to the placebo group, all of whom received their assigned intervention. Survivors in the heparin group (n=97) had similar SF-36 Physical Function Scores at day 60 compared to the placebo group (n=94; mean 53·6 [SD 31·6] vs 48·7 [35·7]; difference 4·9 [95% CI -4·8 to 14·5]; p=0·32). Compared with the placebo group, the heparin group had fewer cases of ARDS develop to day 5 among the at-risk patients (nine [15%] of 62 patients vs 21 [30%] of 71 patients; hazard ratio 0·46 [95% CI 0·22 to 0·98]; p=0·0431), less deterioration of the MLIS to day 5 (difference -0·14 [-0·26 to -0·02]; p=0·0215), similar day 60 mortality (23 [18%] of 127 patients vs 18 [15%] of 123 patients; odds ratio [OR] 1·29 [95% CI 0·66 to 2·53]; p=0·46), and more day 60 survivors at home (86 [87%] of 99 patients vs 73 [73%] of 100 patients; OR 2·45 [1·18 to 5·08]; p=0·0165). A similar number of serious adverse events occurred in each group (seven [5%] of 128 patients in the heparin group vs three [2%] of 124 patients in the placebo group; OR 2·33 [0·59 to 9·24]; p=0·23), which were a transient increase in airway pressure during nebulisation (n=3 in the heparin group), major non-pulmonary bleeding (n=2 in each group), haemoptysis (n=1 in the heparin group), tracheotomy site bleeding (n=1 in the heparin group), and hypoxaemia during nebulisation (n=1 in the placebo group). INTERPRETATION: In patients with or at risk of ARDS, nebulised heparin did not improve self-reported performance of daily physical activities, but was well tolerated and exploratory outcomes suggest less progression of lung injury and earlier return home. Further research is justified to establish if nebulised heparin accelerates recovery in those who have or are at risk of ARDS. FUNDING: Rowe Family Foundation, TR and RB Ditchfield Medical Research Endowment Fund, Patricia Madigan Charitable Trust, and The J and R McGauran Trust Fund.


Assuntos
Cuidados Críticos/métodos , Heparina/administração & dosagem , Respiração Artificial/efeitos adversos , Síndrome do Desconforto Respiratório/epidemiologia , Atividades Cotidianas , Administração por Inalação , Adulto , Idoso , Austrália/epidemiologia , Método Duplo-Cego , Feminino , Hemoptise/induzido quimicamente , Hemoptise/epidemiologia , Heparina/efeitos adversos , Mortalidade Hospitalar , Humanos , Hipóxia/induzido quimicamente , Hipóxia/epidemiologia , Incidência , Masculino , Pessoa de Meia-Idade , Nebulizadores e Vaporizadores , Placebos/administração & dosagem , Placebos/efeitos adversos , Síndrome do Desconforto Respiratório/diagnóstico , Síndrome do Desconforto Respiratório/etiologia , Síndrome do Desconforto Respiratório/prevenção & controle , Autorrelato/estatística & dados numéricos , Índice de Gravidade de Doença , Sobreviventes/estatística & dados numéricos , Fatores de Tempo , Resultado do Tratamento
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