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1.
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 , Hemorragia/induzido quimicamente , Heparina/efeitos adversos , Espaço Retroperitoneal , Anticoagulantes/administração & dosagem , Anticoagulantes/uso terapêutico , /diagnóstico por imagem , Esquema de Medicação , Evolução Fatal , Feminino , Heparina/administração & dosagem , Heparina/uso terapêutico , Humanos , Pessoa de Meia-Idade , Radiografia , Tomografia Computadorizada por Raios X , Tromboembolia Venosa/prevenção & controle
2.
Infez Med ; 29(1): 1-9, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33664168

RESUMO

In this review, we summarize the possible mechanisms of COVID-19-associated coagulopathy and compare its features to other similar conditions. The recent COVID-19 pandemic has caused enormous mortality and morbidity worldwide. It is important to note that COVID-19-associated thrombotic events play a huge role in the morbidity of this disease. Interestingly, it has been observed that this complication may occur despite prophylactic anticoagulant therapy. Recent studies on COVID-19-associated coagulopathy revealed that the COVID-19-associated hypercoagulability is more frequently observed among those with a severe course of the disease. Various mechanisms have been suggested as explanations for this condition and possible underlying etiologies.


Assuntos
Transtornos da Coagulação Sanguínea/etiologia , /complicações , /metabolismo , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Transtornos da Coagulação Sanguínea/metabolismo , Endotélio Vascular/metabolismo , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Hemostasia , Heparina/efeitos adversos , Humanos , Interleucina-10/sangue , Interleucina-6/sangue , Receptores de Interleucina-2/sangue , Trombofilia/etiologia , Trombose/etiologia , Fator de Necrose Tumoral alfa/sangue , Internalização do Vírus
3.
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 de Plaquetas/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 de Plaquetas/administração & dosagem , Transfusão de Plaquetas , Trombocitopenia/terapia , Tirofibana/administração & dosagem
8.
Am J Hematol ; 96(3): 320-329, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33326124

RESUMO

IgG-specific and polyspecific PF4-dependent enzyme-immunoassays (EIAs) have exceptionally high sensitivity (≥99%) for diagnosis of heparin-induced thrombocytopenia (HIT), a drug reaction caused by platelet-activating antibodies detectable by serotonin-release assay (SRA). The IgG-specific EIAs are recommended for screening, as their high sensitivity is accompanied by relatively high specificity vis-à-vis polyspecific EIAs. We investigated the frequency of SRA-positive/EIA-negative (SRA+/EIA-) HIT, prompted by referral to our reference HIT laboratory of serial blood samples from a patient ("index case") with false-negative IgG-specific EIAs. Despite initial clinical suspicion for HIT, repeat negative IgG-specific EIAs prompted heparin resumption, which triggered recurrent thrombocytopenia and near-fatal cardiac arrest, indicating likely post-heparin HIT-associated anaphylactoid reaction. Further investigations revealed a strong-positive SRA, whether performed with heparin alone, PF4 alone, or PF4/heparin, with inhibition by Fc receptor-blocking monoclonal antibody (indicating IgG-mediated platelet activation); however, five different IgG-specific immunoassays yielded primarily negative (or weak-positive) results. To investigate the frequency of SRA+/EIA- HIT, we reviewed the laboratory and clinical features of patients with this serological profile during a 6-year period in which our reference laboratory investigated for HIT using both SRA and IgG-specific EIA. Although ~0.2% of 8546 patients had an SRA+/EIA- profile, further review of 15 such cases indicated clerical/laboratory misclassification or false-positive SRA in all, with no SRA+/EIA- HIT case identified. We conclude that while SRA+/EIA- HIT is possible-as shown by our index case-this clinical picture is exceptionally uncommon. Moreover, the requirement for a positive EIA is a useful quality control maneuver that reduces risk of reporting a false-positive SRA result.


Assuntos
Anafilaxia/induzido quimicamente , Anticoagulantes/efeitos adversos , Autoanticorpos/sangue , Autoantígenos/imunologia , Plaquetas/metabolismo , Heparina/efeitos adversos , Técnicas Imunoenzimáticas/métodos , Imunoglobulina G/sangue , Ativação Plaquetária/imunologia , Fator Plaquetário 4/imunologia , Serotonina/sangue , Trombocitopenia/diagnóstico , Adulto , Anticoagulantes/uso terapêutico , Autoanticorpos/imunologia , Quimioterapia Combinada , Reações Falso-Negativas , Feminino , Parada Cardíaca , Heparina/uso terapêutico , Humanos , Imunoglobulina G/imunologia , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Erros Médicos , Obesidade/complicações , Embolia Pulmonar/complicações , Embolia Pulmonar/tratamento farmacológico , Recidiva , Sensibilidade e Especificidade , Trombocitopenia/induzido quimicamente , Trombose Venosa/complicações , Trombose Venosa/tratamento farmacológico , Varfarina/uso terapêutico
9.
Cochrane Database Syst Rev ; 12: CD008500, 2020 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-33337539

RESUMO

BACKGROUND: Venous thromboembolism (VTE) often complicates the clinical course of cancer. The risk is further increased by chemotherapy, but the trade-off between safety and efficacy of primary thromboprophylaxis in cancer patients treated with chemotherapy is uncertain. This is the third update of a review first published in February 2012. OBJECTIVES: To assess the efficacy and safety of primary thromboprophylaxis for VTE in ambulatory cancer patients receiving chemotherapy compared with placebo or no thromboprophylaxis, or an active control intervention. SEARCH METHODS: For this update, the Cochrane Vascular Information Specialist searched the Cochrane Vascular, CENTRAL, MEDLINE, Embase and CINAHL databases and World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 3 August 2020. We also searched the reference lists of identified studies and contacted content experts and trialists for relevant references. SELECTION CRITERIA: Randomised controlled trials comparing any oral or parenteral anticoagulant or mechanical intervention to no thromboprophylaxis or placebo, or comparing two different anticoagulants. DATA COLLECTION AND ANALYSIS: We extracted data on risk of bias, participant characteristics, interventions, and outcomes including symptomatic VTE and major bleeding as the primary effectiveness and safety outcomes, respectively. We applied GRADE to assess the certainty of evidence. MAIN RESULTS: We identified six additional randomised controlled trials (3326 participants) for this update, bringing the included study total to 32 (15,678 participants), all evaluating pharmacological interventions and performed mainly in people with locally advanced or metastatic cancer. The certainty of the evidence ranged from high to very low across the different outcomes and comparisons. The main limiting factors were imprecision and risk of bias. Thromboprophylaxis with direct oral anticoagulants (direct factor Xa inhibitors apixaban and rivaroxaban) may decrease the incidence of symptomatic VTE (risk ratio (RR) 0.43, 95% confidence interval (CI) 0.18 to 1.06; 3 studies, 1526 participants; low-certainty evidence); and probably increases the risk of major bleeding compared with placebo (RR 1.74, 95% CI 0.82 to 3.68; 3 studies, 1494 participants; moderate-certainty evidence). When compared with no thromboprophylaxis, low-molecular-weight heparin (LMWH) reduced the incidence of symptomatic VTE (RR 0.62, 95% CI 0.46 to 0.83; 11 studies, 3931 participants; high-certainty evidence); and probably increased the risk of major bleeding events (RR 1.63, 95% CI 1.12 to 2.35; 15 studies, 7282 participants; moderate-certainty evidence). In participants with multiple myeloma, LMWH resulted in lower symptomatic VTE compared with the vitamin K antagonist warfarin (RR 0.33, 95% CI 0.14 to 0.83; 1 study, 439 participants; high-certainty evidence), while LMWH probably lowers symptomatic VTE more than aspirin (RR 0.51, 95% CI 0.22 to 1.17; 2 studies, 781 participants; moderate-certainty evidence). Major bleeding was observed in none of the participants with multiple myeloma treated with LMWH or warfarin and in less than 1% of those treated with aspirin. Only one study evaluated unfractionated heparin against no thromboprophylaxis, but did not report on VTE or major bleeding. When compared with placebo or no thromboprophylaxis, warfarin may importantly reduce symptomatic VTE (RR 0.15, 95% CI 0.02 to 1.20; 1 study, 311 participants; low-certainty evidence) and may result in a large increase in major bleeding (RR 3.82, 95% CI 0.97 to 15.04; 4 studies, 994 participants; low-certainty evidence). One study evaluated antithrombin versus no antithrombin in children. This study did not report on symptomatic VTE but did report any VTE (symptomatic and incidental VTE). The effect of antithrombin on any VTE and major bleeding is uncertain (any VTE: RR 0.84, 95% CI 0.41 to 1.73; major bleeding: RR 0.78, 95% CI 0.03 to 18.57; 1 study, 85 participants; very low-certainty evidence). AUTHORS' CONCLUSIONS: In ambulatory cancer patients, primary thromboprophylaxis with direct factor Xa inhibitors may reduce the incidence of symptomatic VTE (low-certainty evidence) and probably increases the risk of major bleeding (moderate-certainty evidence) when compared with placebo. LMWH decreases the incidence of symptomatic VTE (high-certainty evidence), but increases the risk of major bleeding (moderate-certainty evidence) when compared with placebo or no thromboprophylaxis. Evidence for the use of thromboprophylaxis with anticoagulants other than direct factor Xa inhibitors and LMWH is limited. More studies are warranted to evaluate the efficacy and safety of primary prophylaxis in specific types of chemotherapeutic agents and types of cancer, such as gastrointestinal or genitourinary cancer.


Assuntos
Assistência Ambulatorial , Anticoagulantes/uso terapêutico , Neoplasias/tratamento farmacológico , Prevenção Primária/métodos , Tromboembolia Venosa/prevenção & controle , Adulto , Anticoagulantes/efeitos adversos , Antineoplásicos/efeitos adversos , Antitrombinas/uso terapêutico , Viés , Criança , Inibidores do Fator Xa/uso terapêutico , Hemorragia/induzido quimicamente , Heparina/efeitos adversos , Heparina/uso terapêutico , Heparina de Baixo Peso Molecular/efeitos adversos , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Neoplasias/complicações , Embolia Pulmonar/etiologia , Embolia Pulmonar/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto , Tromboembolia Venosa/etiologia , Varfarina/efeitos adversos , Varfarina/uso terapêutico
10.
Cochrane Database Syst Rev ; 12: CD012467, 2020 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-33314078

RESUMO

BACKGROUND: Acute kidney injury (AKI) is a major comorbidity in hospitalised patients. Patients with severe AKI require continuous renal replacement therapy (CRRT) when they are haemodynamically unstable. CRRT is prescribed assuming it is delivered over 24 hours. However, it is interrupted when the extracorporeal circuits clot and the replacement is required. The interruption may impair the solute clearance as it causes under dosing of CRRT. To prevent the circuit clotting, anticoagulation drugs are frequently used. OBJECTIVES: To assess the benefits and harms of pharmacological interventions for preventing clotting in the extracorporeal circuits during CRRT. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 12 September 2019 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: We selected randomised controlled trials (RCTs or cluster RCTs) and quasi-RCTs of pharmacological interventions to prevent clotting of extracorporeal circuits during CRRT. DATA COLLECTION AND ANALYSIS: Data were abstracted and assessed independently by two authors. Dichotomous outcomes were calculated as risk ratio (RR) with 95% confidence intervals (CI). The primary review outcomes were major bleeding, successful prevention of clotting (no need of circuit change in the first 24 hours for any reason), and death. Evidence certainty was determined using the Grading of Recommendation Assessment, Development, and Evaluation (GRADE) approach. MAIN RESULTS: A total of 34 completed studies (1960 participants) were included in this review. We identified seven ongoing studies which we plan to assess in a future update of this review. No included studies were free from risk of bias. We rated 30 studies for performance bias and detection bias as high risk of bias. We rated 18 studies for random sequence generation,ààsix studies for the allocation concealment, three studies for performance bias, three studies for detection bias,à nine studies for attrition bias,à14 studies for selective reporting and nine studies for the other potential source of bias, as having low risk of bias. We identified eight studies (581 participants) that compared citrate with unfractionated heparin (UFH). Compared to UFH, citrate probably reduces major bleeding (RR 0.22, 95% CI 0.08 to 0.62; moderate certainty evidence) and probably increases successful prevention of clotting (RR 1.44, 95% CI 1.10 to 1.87; moderate certainty evidence). Citrate may have little or no effect on death at 28 days (RR 1.06, 95% CI 0.86 to 1.30, moderate certainty evidence). Citrate versus UFH may reduce the number of participants who drop out of treatment due to adverse events (RR 0.47, 95% CI 0.15 to 1.49; low certainty evidence). Compared to UFH, citrate may make little or no difference to the recovery of kidney function (RR 1.04, 95% CI 0.89 to 1.21; low certainty evidence). Compared to UFH, citrate may reduceàthrombocytopenia (RR 0.39, 95% CI 0.14 to 1.03; low certainty evidence). It was uncertain whether citrate reduces a cost to health care services because of inadequate data. For low molecular weight heparin (LMWH) versus UFH, six studies (250 participants) were identified. Compared to LMWH, UFH may reduce major bleeding (0.58, 95% CI 0.13 to 2.58; low certainty evidence). It is uncertain whether UFH versus LMWH reduces death at 28 days or leads to successful prevention of clotting. Compared to LMWH, UFH may reduce the number of patient dropouts from adverse events (RR 0.29, 95% CI 0.02 to 3.53; low certainty evidence). It was uncertain whether UFH versus LMWH leads to the recovery of kidney function because no included studies reported this outcome. It was uncertain whether UFH versus LMWH leads to thrombocytopenia. It was uncertain whether UFH reduces a cost to health care services because of inadequate data. For the comparison of UFH to no anticoagulation, one study (10 participants) was identified. It is uncertain whether UFH compare to no anticoagulation leads to more major bleeding. It is uncertain whether UFH improves successful prevention of clotting in the first 24 hours, death at 28 days, the number of patient dropouts due to adverse events, recovery of kidney function, thrombocytopenia, or cost to health care services because no study reported these outcomes. For the comparison ofàcitrate to no anticoagulation,àno completed study was identified. AUTHORS' CONCLUSIONS: Currently,àavailable evidence does not support the overall superiority of any anticoagulant to another. Compared to UFH, citrate probably reduces major bleeding and prevents clotting and probably has little or no effect on death at 28 days. For other pharmacological anticoagulation methods, there is no available data showing overall superiority to citrate or no pharmacological anticoagulation. Further studies are needed to identify patient populations in which CRRT should commence with no pharmacological anticoagulation or with citrate.


Assuntos
Lesão Renal Aguda/terapia , Anticoagulantes/administração & dosagem , Coagulação Sanguínea/efeitos dos fármacos , Obstrução do Cateter , Terapia de Substituição Renal Contínua/instrumentação , Lesão Renal Aguda/mortalidade , Anticoagulantes/efeitos adversos , Viés , Obstrução do Cateter/etiologia , Ácido Cítrico/administração & dosagem , Ácido Cítrico/efeitos adversos , Terapia de Substituição Renal Contínua/efeitos adversos , Terapia de Substituição Renal Contínua/mortalidade , Filtração/instrumentação , Hemorragia/induzido quimicamente , Hemorragia/prevenção & controle , Heparina/administração & dosagem , Heparina/efeitos adversos , Heparina de Baixo Peso Molecular/administração & dosagem , Heparina de Baixo Peso Molecular/efeitos adversos , Humanos , Rim/fisiologia , Pacientes Desistentes do Tratamento , Ensaios Clínicos Controlados Aleatórios como Assunto , Recuperação de Função Fisiológica/efeitos dos fármacos , Trombocitopenia/prevenção & controle
11.
Trials ; 21(1): 920, 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33176886

RESUMO

OBJECTIVES: The primary objective is to test if heparin added to a standard regional anticoagulation protocol based on citrate is able to reduce dialysis circuit losses by clotting without increasing the risk of thrombocytopenia or bleeding, in patients with COVID-19 with acute kidney injury requiring dialysis. TRIAL DESIGN: Randomized, parallel-group, open-label trial, with two arms (ratio 1:1) comparing different continuous renal replacement therapy anticoagulation strategies. PARTICIPANTS: Eligibility conditions: All ICU patients of University of Sao Paulo General Hospital (Hospital das Clínicas), Brazil will be screened for eligibility conditions. Adults (> 18 years old) with confirmed COVID-19 and acute kidney injury requiring dialysis with agreement between ICU and nephrology teams for the introduction of renal continuous replacement therapy in daily ICU rounds. Continuous renal replacement therapy will be prescribed by consulting nephrologists based on standard clinical guidelines, including acute kidney injury with hemodynamic instability plus hyperkalemia, severe acidosis, volume overload, respiratory distress, multiorgan failure or some combination of these factors. DATA COLLECTION: Patients demographics and associated clinical data and comorbidities will be recorded at ICU entry. Demographic information will include the patient's age, sex, and admission dates. Clinical data comprise comorbidities, APACHE 2, SAPS 3, need for mechanical ventilation, and use of vasopressor drugs. Physiological data collected by the day of CRRT start will be vital signs, the arterial oxygen tension/fraction of inspired oxygen (PaO2/FiO2) index, and serum creatinine, blood urea nitrogen, bilirubin, hemoglobin, hematocrit, platelets, white blood cell count levels and Peak D-dimer levels. Patients will be analyzed for the first 72h of CRRT, and they will be evaluated regarding clinical variables, filter patency and any adverse events that could be related to the anticoagulation choice, as bleeding (mild or major) or low platelets counts (<100.000 ui/uL) during treatment period. Mild and major bleeding will be defined by hemorrhagic event without clinical impact or hemoglobin (Hb) fall lesser than 1g/dL and hemorrhagic event with clinical impact or Hb fall higher than 1g/dL, respectively. EXCLUSION CRITERIA: Hypersensitivity to any of the substances going to be used in the study (Citric acid dextrosol 2.2% and unfractionated heparin); Previous diagnosis of coagulopathy or thrombophilia; Contraindication to the use of unfractionated heparin; Risk of citrate poisoning - (Lactate> 30 mg/dL, international normalized ratio > 2.5, Total bilirubin> 15 mg/dL); Pregnancy; Patients unlikely to survive for more than 24 hours. The trial is being undertaken at the University of Sao Paulo General Hospital (Hospital das Clinicas), Brazil. INTERVENTION AND COMPARATOR: Group A (control) - Patients on continuous renal replacement therapy (blood flow 150 ml/min, dose of 30 mL/Kg/h) receiving anticoagulation with sodium citrate at 4 mmol/L Group B (experiment): Patients on continuous hemodialysis (blood flow 150 mL/min, dose of 30 mL/Kg/h) receiving anticoagulation with sodium citrate at 4 mmol/L associated with unfractionated heparin at 10 U/Kg/h. MAIN OUTCOMES: The percentage of clotted dialyzers within 72 hours in each of the studied groups (Primary outcome) Secondary outcomes: Number of dialyzers used in the first 72 hours of dialysis protocol, Mortality in the first 72 h of dialysis protocol, Bleeding events (Major or minor) in the first 72 h of dialysis protocol, Thrombocytopenia (less than 50.000 platelets) proportion in the first 72 h of dialysis protocol, Dialysis efficiency (Urea sieving) - variation in urea sieving between the first, second and third days of dialysis protocol, Continuous renal replacement therapy pressures (Arterial, Venous, dialysate and pre-filter pressure) in the first 72 h of dialysis protocol, in-hospital mortality. RANDOMIZATION: RedCap→ randomization - 2 blocks randomization by D-dimer level (5000ng/dL cut-off) and catheter site (Right Internal Jugular versus other sites) with 1:1 allocation ratio. BLINDING (MASKING): No blinding - Open label format NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): Total number of patients 90 (45 per group) TRIAL STATUS: Trial version 2.0 - ongoing recruitment. First recruitment: June 29, 2020 Estimated date for last recruitment: December 31, 2020 TRIAL REGISTRATION: Responsible Party: University of Sao Paulo General Hospital (Hospital das Clinicas) ClinicalTrials.gov Identifier: NCT04487990 , registered July 27, 2020, ReBec www.ensaiosclinicos.gov.br/rg/RBR-45kf9p/ Other Study ID Numbers: U1111-1252-0194 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1) In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Assuntos
Lesão Renal Aguda , Infecções por Coronavirus , Monitoramento de Medicamentos/métodos , Heparina , Pandemias , Pneumonia Viral , Diálise Renal , Trombose/prevenção & controle , Lesão Renal Aguda/etiologia , Lesão Renal Aguda/terapia , Adulto , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Coagulação Sanguínea/efeitos dos fármacos , Infecções por Coronavirus/sangue , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Hemoglobinas/análise , Hemorragia/etiologia , Hemorragia/prevenção & controle , Heparina/administração & dosagem , Heparina/efeitos adversos , Humanos , Masculino , Avaliação de Resultados em Cuidados de Saúde , Pneumonia Viral/sangue , Pneumonia Viral/complicações , Pneumonia Viral/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Diálise Renal/efeitos adversos , Diálise Renal/métodos , Risco Ajustado/métodos , Trombocitopenia/etiologia , Trombocitopenia/prevenção & controle , Trombose/complicações
13.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 5374-5377, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33019196

RESUMO

Unfractionated heparin (UFH) is commonly used in the intensive care unit (ICU) to prevent blood clotting. Recently, many researchers focus on the development of data- driven methods to solve UFH related problems, which usually involves time series analysis. The performance of data-driven methods depends on whether the inter-correlation of attributes (or variables) in the dataset is closely examined and addressed. This study performs attribute selection, optimal time delay and inter-attributes relations on ICU time series data, in order to provide insights of time series data for UFH related problems. Medical records of 3211 patients with 22 attributes extracted from MIMIC (Medical Information Mart for Intensive Care) III database are used for the experiment. Experimental result shows that some of commonly selected attributes in the literature are less sensitive to the variations of UFH injection. Furthermore, some attributes are inter-dependent, which can increase the complexity of data-driven models, implying that the number of attributes could be reduced. There are 9 attributes found highly related and fast responding in 22 commonly used attributes. This study shows strong potential to provide clinicians with information about sensitive attributes that can help determine the UFH injection policy in ICU.


Assuntos
Heparina , Trombose , Coagulação Sanguínea , Heparina/efeitos adversos , Humanos , Injeções , Projetos de Pesquisa
14.
JAMA ; 324(16): 1629-1639, 2020 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-33095849

RESUMO

Importance: Although current guidelines suggest the use of regional citrate anticoagulation (which involves the addition of a citrate solution to the blood before the filter of the extracorporeal dialysis circuit) as first-line treatment for continuous kidney replacement therapy in critically ill patients, the evidence for this recommendation is based on few clinical trials and meta-analyses. Objective: To determine the effect of regional citrate anticoagulation, compared with systemic heparin anticoagulation, on filter life span and mortality. Design, Setting, and Participants: A parallel-group, randomized multicenter clinical trial in 26 centers across Germany was conducted between March 2016 and December 2018 (final date of follow-up, January 21, 2020). The trial was terminated early after 596 critically ill patients with severe acute kidney injury or clinical indications for initiation of kidney replacement therapy had been enrolled. Interventions: Patients were randomized to receive either regional citrate anticoagulation (n = 300), which consisted of a target ionized calcium level of 1.0 to 1.40 mg/dL, or systemic heparin anticoagulation (n = 296), which consisted of a target activated partial thromboplastin time of 45 to 60 seconds, for continuous kidney replacement therapy. Main Outcomes and Measures: Coprimary outcomes were filter life span and 90-day mortality. Secondary end points included bleeding complications and new infections. Results: Among 638 patients randomized, 596 (93.4%) (mean age, 67.5 years; 183 [30.7%] women) completed the trial. In the regional citrate group vs systemic heparin group, median filter life span was 47 hours (interquartile range [IQR], 19-70 hours) vs 26 hours (IQR, 12-51 hours) (difference, 15 hours [95% CI, 11 to 20 hours]; P < .001). Ninety-day all-cause mortality occurred in 150 of 300 patients vs 156 of 296 patients (Kaplan-Meier estimator percentages, 51.2% vs 53.6%; unadjusted difference, -2.4% [95% CI, -10.5% to 5.8%]; unadjusted hazard ratio, 0.91 [95% CI, 0.72 to 1.13]; unadjusted P = .38; adjusted difference, -6.1% [95% CI, -12.6% to 0.4%]; primary adjusted hazard ratio, 0.79 [95% CI, 0.63 to 1.004]; primary adjusted P = .054). Of 38 prespecified secondary end points, 34 showed no significant difference. Compared with the systemic heparin group, the regional citrate group had significantly fewer bleeding complications (15/300 [5.1%] vs 49/296 [16.9%]; difference, -11.8% [95% CI, -16.8% to -6.8%]; P < .001) and significantly more new infections (204/300 [68.0%] vs 164/296 [55.4%]; difference, 12.6% [95% CI, 4.9% to 20.3%]; P = .002). Conclusions and Relevance: Among critically ill patients with acute kidney injury receiving continuous kidney replacement therapy, anticoagulation with regional citrate, compared with systemic heparin anticoagulation, resulted in significantly longer filter life span. The trial was terminated early and was therefore underpowered to reach conclusions about the effect of anticoagulation strategy on mortality. Trial Registration: ClinicalTrials.gov Identifier: NCT02669589.


Assuntos
Lesão Renal Aguda/terapia , Anticoagulantes/administração & dosagem , Ácido Cítrico/administração & dosagem , Terapia de Substituição Renal Contínua/instrumentação , Heparina/administração & dosagem , Lesão Renal Aguda/sangue , Lesão Renal Aguda/mortalidade , Idoso , Anticoagulantes/efeitos adversos , Cálcio/sangue , Ácido Cítrico/efeitos adversos , Terapia de Substituição Renal Contínua/mortalidade , Estado Terminal , Término Precoce de Ensaios Clínicos , Feminino , Filtração/instrumentação , Alemanha , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Heparina/efeitos adversos , Humanos , Infecções/epidemiologia , Estimativa de Kaplan-Meier , Masculino , Tempo de Tromboplastina Parcial , Modelos de Riscos Proporcionais , Fatores de Tempo
15.
Int Heart J ; 61(5): 865-871, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32921667

RESUMO

Bleeding complication has been considered as a serious problem in current percutaneous coronary interventions (PCI). Fortunately, several groups have already reported the effectiveness of protamine use just after PCI to immediately remove any arterial sheath. However, there is a concern that protamine reversal may increase non-occlusive thrombus and, in turn, lead to mid-term cardiovascular events such as target vessel revascularization (TVR) or stent thrombosis. Thus, the purpose of this study was to evaluate whether protamine use following elective PCI was associated with mid-term clinical outcomes. In total, 472 patients were included in this study; subsequently, they were divided into protamine group (n = 142) and non-protamine group (n = 330). The primary endpoint was the composite of ischemia-driven TVR and stent thrombosis. The median follow-up period was determined to be at 562 days. In total, 32 primary endpoints were observed during the study period, and the incidence of primary endpoints tended to be greater in the protamine group than in the non-protamine group (P = 0.056). However, the lesion length, the degree of calcification, and the prevalence of hemodialysis were significantly determined greater in the protamine group than in the non-protamine group. In the multivariate Cox proportional hazards model, the use of protamine (versus non-protamine: hazard ratio 0.542 and 95% confidence interval 0.217-1.355, P = 0.191) was deemed not to be associated with the primary endpoint after controlling legion length, calcification, and hemodialysis. In conclusion, immediate protamine use following elective PCI did not increase mid-term ischemia-driven TVR or stent thrombosis. However, immediate protamine use after PCI should be discussed further for the safety of the patient.


Assuntos
Estenose Coronária/cirurgia , Antagonistas de Heparina/uso terapêutico , Intervenção Coronária Percutânea/métodos , Complicações Pós-Operatórias/epidemiologia , Hemorragia Pós-Operatória/prevenção & controle , Protaminas/uso terapêutico , Trombose/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Estudos de Casos e Controles , Estenose Coronária/epidemiologia , Procedimentos Cirúrgicos Eletivos/métodos , Feminino , Heparina/efeitos adversos , Humanos , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Revascularização Miocárdica/estatística & dados numéricos , Complicações Pós-Operatórias/induzido quimicamente , Hemorragia Pós-Operatória/induzido quimicamente , Modelos de Riscos Proporcionais , Diálise Renal , Estudos Retrospectivos , Stents , Trombose/induzido quimicamente , Calcificação Vascular/epidemiologia
16.
Lancet Haematol ; 7(10): e746-e755, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32976752

RESUMO

BACKGROUND: Study-level meta-analyses provide high-certainty evidence that heparin reduces the risk of symptomatic venous thromboembolism for patients with cancer; however, whether the benefits and harms associated with heparin differ by cancer type is unclear. This individual participant data meta-analysis of randomised controlled trials examines the effect of heparin on survival, venous thromboembolism, and bleeding in patients with cancer in general and by type. METHODS: In this systematic review and meta-analysis we searched MEDLINE, Embase, and The Cochrane Library for randomised controlled trials comparing parenteral anticoagulants with placebo or standard care in ambulatory patients with solid tumours and no indication for anticoagulation published from the inception of each database to January 14, 2017, and updated it on May 14, 2020, without language restrictions. We calculated the effect of parenteral anticoagulant administration on all-cause mortality, venous thromboembolism occurrence, and bleeding related outcomes through multivariable hierarchical models with patient-level variables as fixed effects and a categorical trial variable as a random effect, adjusting for age, cancer type, and metastatic status. Interaction terms were tested to investigate effects in predefined subgroups. This study is registered with PROSPERO, CRD42013003526. FINDINGS: We obtained individual participant data from 14 of 20 eligible randomised controlled trials (8278 [79%] of 10 431 participants; 4139 included in the low-molecular-weight heparin group and 4139 in the control group). Meta-analysis showed an adjusted relative risk (RR) of mortality at 1 year of 0·99 (95% CI 0·93-1·06) and a hazard ratio of 1·01 (95% CI 0·96-1·07). The number of patients with venous thromboembolic events was 158 (4·0%) of 3958 with available data in the low-molecular-weight heparin group compared with 279 (7·1%) of 3957 in the control group. Major bleeding events occurred in 71 (1·7%) of 4139 patients in the control population and 88 (2·1%) in the low-molecular-weight heparin group, and minor bleeding events in 478 (12·1%) of 3945 patients with available data in the control group and 652 (16·6%) of 3937 patients in the low-molecular-weight heparin group. The adjusted RR was 0·58 (95% CI 0·47-0·71) for venous thromboembolism, 1·27 (0·92-1·74) for major bleeding, and 1·34 (1·19-1·51) for minor bleeding. Prespecified subgroup analysis of venous thromboembolism occurrence by cancer type identified the most certain benefit from heparin treatment in patients with lung cancer (RR 0·59 [95% CI 0·42-0·81]), which dominated the overall reduction in venous thromboembolism. Certainty of the evidence for the outcomes ranged from moderate to high. INTERPRETATION: Low-molecular-weight heparin reduces risk of venous thromboembolism without increasing risk of major bleeding compared with placebo or standard care in patients with solid tumours, but it does not improve survival. FUNDING: Canadian Institutes of Health Research.


Assuntos
Anticoagulantes/uso terapêutico , Heparina/uso terapêutico , Neoplasias/complicações , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controle , Anticoagulantes/efeitos adversos , Hemorragia/induzido quimicamente , Heparina/efeitos adversos , Heparina de Baixo Peso Molecular/efeitos adversos , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Análise de Sobrevida
18.
Vnitr Lek ; 66(4): 242-248, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32972188

RESUMO

Heparin-induced thrombocytopenia (HIT) is an immunologically-mediated complication, which usually follows heparin exposition, less frequently exposition to other drugs or even occurs spontaneously. The type of heparin, its dose and mode of application as well as the exposition time, major trauma or operation, and obesity represent the main risk factors for HIT. The probability of HIT correlates with so-called 4T-score. A confirmatory laboratory diagnostic should be exclusively reserved for patients with a medium to a high probability of HIT development (more than 3 points in 4T-score). The screening method is based on serological detection of antibodies against heparin-platelet factor-4 complexes; confirmation tests aim to identify the activation of platelets. The treatment of HIT requires an immediate interruption of heparin application and rigorous antithrombotic treatment with an alternative agent. Herein authors describe a clinical case of HIT manifested as an extreme urticarial reaction in the location of nadroparin application as well as thrombosis of deep subcutaneous veins in a polymorbid obese patient with an extensive and infected burn. Due to timely diagnosis and fondaparinux treatment, no more severe thrombotic events occurred in this patient.


Assuntos
Trombocitopenia , Trombose , Anticoagulantes/efeitos adversos , Fondaparinux , Heparina/efeitos adversos , Humanos , Trombocitopenia/induzido quimicamente , Trombocitopenia/diagnóstico
19.
J Stroke Cerebrovasc Dis ; 29(10): 105052, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32912529

RESUMO

BACKROUND AND PURPOSE: Role of peri-procedural heparin as an adjuvant treatment during mechanical thrombectomy (MT) for patients contra-indicated for alteplase remains a source of debate. METHODS: We included patients from the multicenter French register ETIS that underwent MT without administration of alteplase, and compared patients who received heparin during MT with patients who did not. Heparin impact on outcome were analyzed regarding final TICI score, NIHSS at day one, modified rankin scale (mRS) and intracranial hemorrhagic transformation on imaging at day one. RESULTS: Over 1031 patients, 751 were included between January 2015 and June 2018 in 6 different centers, and 223 (26.69%) received heparin. Heparin administration was associated with a significant deleterious effect on NIHSS at 24h [adjusted OR = 1.2; p = 0.02], mRS at 3 months [adjusted OR 1.58; p = 0.03], and on complete reperfusion [TICI 3 adjusted OR 0.68; p = 0.02]. Heparin administration was associated with a significant reduction of hemorrhagic transformation [adjusted OR 0.48; p = 0.00005]. CONCLUSIONS: Heparin administration during MT seems deleterious for reperfusion and functional outcome. Randomized trials are needed to identify the role of antithrombotic treatments, such as heparin, in the setting of acute ischemic stroke management.


Assuntos
Anticoagulantes/efeitos adversos , Isquemia Encefálica/terapia , Contraindicações de Medicamentos , Fibrinolíticos/efeitos adversos , Heparina/administração & dosagem , Acidente Vascular Cerebral/terapia , Trombectomia , Terapia Trombolítica/efeitos adversos , Ativador de Plasminogênio Tecidual/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/administração & dosagem , Isquemia Encefálica/diagnóstico , Feminino , França , Heparina/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Trombectomia/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
20.
J Int Med Res ; 48(8): 300060520951040, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32865072

RESUMO

Spontaneous epistaxis in patients with COVID-19 can represent a clinical challenge with respect to both the risk of contamination and the treatment options. We herein present the data of 30 patients with COVID-19 who developed spontaneous epistaxis while hospitalized at Eastern Piedmont Hospital during March and April 2020. All patients received low-molecular-weight heparin during their hospital stay and required supplementary oxygen therapy either by a nasal cannula or continuous positive airway pressure. Both conditions can represent risk factors for developing epistaxis. Prevention of crust formation in patients with rhinitis using a nasal lubricant should be recommended. If any treatment is required, appropriate self-protection is mandatory.


Assuntos
Infecções por Coronavirus/patologia , Epistaxe/patologia , Oxigenoterapia/métodos , Pneumonia Viral/patologia , Idoso , Betacoronavirus , Cânula , Pressão Positiva Contínua nas Vias Aéreas , Epistaxe/virologia , Feminino , Heparina/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa Nasal/lesões , Pandemias
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