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1.
BMC Surg ; 24(1): 162, 2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38762739

RESUMO

OBJECTIVES: To compare the efficacy of nadroparin and fondaparinux sodium for prevention of deep vein thromboembolism (DVT) in lower extremities after total hip arthroplasty (THA) and total knee arthroplasty (TKA). METHODS: A total of 592 patients were enrolled in the study. Clinical data of patients who underwent total hip arthroplasty (THA) and total knee arthroplasty (TKA) in our hospital from December 2021 to September 2022 were retrospectively collected, which mainly included patients' general information, surgery-related information, and DVT-related information. The patients were categorized into the nadroparin group(n = 278) and the fondaparinux sodium group(n = 314) according to the types of anticoagulants used. Anticoagulant therapy began 12-24 h after operation and continued until discharge. DVT prevalence between two groups was compared. The Statistical Package for Social Sciences (SPSS) software version 25 (SPSS, Armonk, NY, USA) was used for statistical analysis. RESULTS: The prevalence of DVT in the nadroparin group and the fondaparinux sodium group was 8.3% (23/278) and 15.0% (47/314), respectively(p = 0.012). Statistical analysis showed that nadroparin group showed a lower prevalence of thrombosis than fondaparinux group (OR = 1.952, P = 0.012). Subgroup analyses showed that nadroparin group had a lower prevalence of DVT than fondaparinux group in some special patients groups such as female patients (OR = 2.258, P = 0.007), patients who are 65-79 years old (OR = 2.796, P = 0.004), patients with hypertension (OR = 2.237, P = 0.042), patients who underwent TKA (OR = 2.091, P = 0.011), and patients who underwent combined spinal-epidural anesthesia (OR = 2.490, P = 0.003) (P < 0.05). CONCLUSION: Nadroparin may have an advantage over fondaparinux sodium in preventing DVT in lower extremities after THA and TKA.


Assuntos
Anticoagulantes , Artroplastia de Quadril , Artroplastia do Joelho , Fondaparinux , Nadroparina , Complicações Pós-Operatórias , Tromboembolia Venosa , Humanos , Fondaparinux/uso terapêutico , Feminino , Masculino , Estudos Retrospectivos , Artroplastia de Quadril/efeitos adversos , Artroplastia do Joelho/efeitos adversos , Nadroparina/uso terapêutico , Nadroparina/administração & dosagem , Pessoa de Meia-Idade , Tromboembolia Venosa/prevenção & controle , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/epidemiologia , Idoso , Anticoagulantes/uso terapêutico , Anticoagulantes/administração & dosagem , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Extremidade Inferior/irrigação sanguínea , Extremidade Inferior/cirurgia , Resultado do Tratamento
2.
BMC Pregnancy Childbirth ; 21(1): 683, 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34620101

RESUMO

OBJECTIVE: To compare three commonly used low-molecular-weight heparins (LWMHs) in the treatment of recurrent spontaneous abortion (RSA) by evaluating the anti-Xa peak levels and adverse reactions. METHODS: In this single-center, observational study, we enrolled 310 patients with RSA in whom anti-Xa levels were measured during pregnancy. Patients were divided into three groups according to the LMWH they used: the nadroparin group, enoxaparin group and dalteparin group. We compared the peak anti-Xa levels and the coagulation status of each group, and analyzed the incidence of adverse reactions, including local allergy, liver and renal dysfunction, and the impact on platelet. RESULTS: Patients in the enoxaparin group had a higher anti-Xa peak level than those in the nadroparin group (0.80 ± 0.22 IU/ml vs. 0.61 ± 0.24 IU/ml; P <  0.0001), although most patients in the three groups reached the target concentration of anti-Xa. Furthermore, patients in the enoxaparin group had a more stable anti-Xa levels during pregnancy. In addition, patients in the nadroparin group had a higher rate of local allergy than those in the enoxaparin group (60.5% vs. 42.5%; P = 0.004) and those in the dalteparin group (60.5% vs. 33.3%; P = 0.002). Further examination by the type of local allergy indicated a dramatic difference in pruritus and induration between the nadroparin group and the other two groups. No difference was found in the incidence of liver and renal dysfunction and thrombocytopenia. CONCLUSION: Compared with nadroparin and daltepatin, enoxaparin showed a better performance regarding anti-Xa levels and the incidence of adverse reactions in the treatment of RSA.


Assuntos
Aborto Habitual/tratamento farmacológico , Anticoagulantes/farmacologia , Anticoagulantes/uso terapêutico , Inibidores do Fator Xa/sangue , Heparina de Baixo Peso Molecular/farmacologia , Heparina de Baixo Peso Molecular/uso terapêutico , Adulto , Anticoagulantes/efeitos adversos , Povo Asiático , Coagulação Sanguínea/efeitos dos fármacos , China/epidemiologia , Dalteparina/administração & dosagem , Hipersensibilidade a Drogas/complicações , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/complicações , Enoxaparina/administração & dosagem , Feminino , Heparina de Baixo Peso Molecular/efeitos adversos , Humanos , Incidência , Nadroparina/administração & dosagem , Gravidez
3.
J Clin Pharm Ther ; 46(2): 539-542, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33277918

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Fondaparinux exhibits a similar mechanism of action as LMWH. Since both of these drugs bind to antithrombin and increase its affinity to factor Xa, fondaparinux is not expected to be an effective alternative anticoagulant to LMWH in case of LMWH resistance. CASE SUMMARY: We report on a case of effective anticoagulation using fondaparinux following total unresponsiveness to high doses of nadroparin administered twice daily, as confirmed via repeated anti-Xa measurements. The antithrombin levels were within the normal range. WHAT IS NEW AND CONCLUSION: To the best of our knowledge, this is the first report of the effective use of fondaparinux in the case of unresponsiveness to LMWH.


Assuntos
Anticoagulantes/uso terapêutico , Fondaparinux/uso terapêutico , Heparina de Baixo Peso Molecular/uso terapêutico , Nadroparina/uso terapêutico , Idoso , Anticoagulantes/administração & dosagem , Anticoagulantes/farmacologia , Coagulação Sanguínea/efeitos dos fármacos , Fondaparinux/administração & dosagem , Fondaparinux/farmacologia , Heparina de Baixo Peso Molecular/administração & dosagem , Heparina de Baixo Peso Molecular/farmacologia , Humanos , Masculino , Nadroparina/administração & dosagem , Nadroparina/farmacologia
4.
Medicine (Baltimore) ; 99(36): e22028, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32899057

RESUMO

Comparison of different anticoagulants in blood management and complications with tranexamic acid (TXA) in total hip arthroplasty (THA) is unclear. Our aim was to compare the efficacy and safety among receiving nadroparin calcium, enoxaparin sodium or rivaroxaban after TXA in THA.150 patients undergoing primary unilateral THA were received 15 mg/kg intravenous TXA (IV-TXA) before skin incision, followed by 1 of nadroparin calcium (Group A), enoxaparin sodium (Group B), or rivaroxaban (Group C) randomly during hospitalization. The primary outcome was hidden blood loss (HBL). Other outcomes such as the maximum hemoglobin (Hb) drop, total blood loss (TBL), the volume of drainage, transfusion rate, length of hospital stay (LOS), and complications were also compared.There were no statistically significant differences in HBL, the maximum hemoglobin (Hb) drop, transfusion rate, and complications among 3 groups. LOS was significantly higher for patients in Group B than Group A (P = .026). Neither deep venous thrombosis (DVT) nor pulmonary embolism (PE) occurred in any group.There were no differences in efficacy and safety in patients undergoing THA receiving nadroparin calcium, enoxaparin sodium, or rivaroxaban after anti-fibrinolysis with TXA.


Assuntos
Anticoagulantes/efeitos adversos , Antifibrinolíticos/efeitos adversos , Perda Sanguínea Cirúrgica/prevenção & controle , Ácido Tranexâmico/efeitos adversos , Administração Intravenosa , Idoso , Anticoagulantes/administração & dosagem , Antifibrinolíticos/administração & dosagem , Artroplastia de Quadril/efeitos adversos , Transfusão de Sangue/estatística & dados numéricos , China/epidemiologia , Enoxaparina/administração & dosagem , Enoxaparina/efeitos adversos , Feminino , Hemoglobinas/análise , Hospitalização , Humanos , Tempo de Internação/tendências , Masculino , Pessoa de Meia-Idade , Nadroparina/administração & dosagem , Nadroparina/efeitos adversos , Sangue Oculto , Estudos Retrospectivos , Rivaroxabana/administração & dosagem , Rivaroxabana/efeitos adversos , Segurança , Ácido Tranexâmico/administração & dosagem , Resultado do Tratamento
5.
Clin Transl Gastroenterol ; 11(9): e00228, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32858573

RESUMO

INTRODUCTION: Anticoagulation therapy in portal vein thrombosis (PVT) in patients with cirrhosis is still a matter of debate. Therefore, the aim of this work was to evaluate the efficacy and safety of nadroparin calcium-warfarin sequential (NWS) anticoagulation therapy in cirrhotic patients and to find an optimal anticoagulation strategy. METHODS: Consecutive cirrhotic patients with PVT who have not received anticoagulation therapy were randomly divided into the NWS therapy group (1-month nadroparin calcium by subcutaneous injection followed by 5-month warfarin by oral administration) and control group (no anticoagulation therapy). Overall recanalization rate of PVT and risks of bleeding were evaluated at the sixth month. RESULTS: Among 64 patients, complete or partial recanalization of PVT was observed in 20/32 NSW therapy group patients vs 11/32 control group patients (62.5% vs 34.4%, P = 0.024), with no statistically significant difference in bleeding rate. Child-Pugh score (P = 0.023), D-dimer < 2.00 µg/mL (P = 0.020), and NWS anticoagulation therapy (P = 0.004) were predictors associated with the recanalization. NWS anticoagulation therapy (P = 0.008) was an independent predicting factor of recanalization. In the NWS therapy group, the Child-Pugh score (P = 0.007) and albumin level (P = 0.004) were improved in the sixth month. DISCUSSION: NWS anticoagulation therapy was effective and safe in PVT patients with cirrhosis and could increase the level of albumin. NWS therapy is safe and easily accepted.


Assuntos
Anticoagulantes/administração & dosagem , Cirrose Hepática/complicações , Veia Porta/diagnóstico por imagem , Trombose Venosa/tratamento farmacológico , Adulto , Anticoagulantes/efeitos adversos , Esquema de Medicação , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Humanos , Cirrose Hepática/sangue , Cirrose Hepática/diagnóstico , Masculino , Pessoa de Meia-Idade , Nadroparina/administração & dosagem , Nadroparina/efeitos adversos , Estudos Prospectivos , Albumina Sérica Humana/análise , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Trombose Venosa/sangue , Trombose Venosa/diagnóstico , Trombose Venosa/etiologia , Varfarina/administração & dosagem , Varfarina/efeitos adversos
6.
J Clin Pharmacol ; 60(12): 1671-1678, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32639644

RESUMO

Hepatotoxicity with low-molecular-weight heparin (LMWH) or fondaparinux is a relatively common adverse reaction. This study assessed the effects of LMWH and fondaparinux on liver function in patients with pulmonary embolism based on a retrospective cohort. As a result, a total of 463 patients with pulmonary embolism and treated with LMWH (enoxaparin sodium or nadroparin calcium) or fondaparinux sodium were included. Liver dysfunction was identified in 79 patients (17.1%), of whom 97.5% had grade 1 drug-induced liver injury (DILI) and 2.5% had grade 2 DILI. The results showed that liver dysfunction usually occurred in the first week after anticoagulant administration, and the liver tests of all patients with liver dysfunction gradually recovered or alleviated at discharge. The multivariable logistic regression analysis indicated that a longer treatment course and hepatitis B surface antigen-positive (HBsAg+) were risk factors for liver dysfunction (P < .05). Moreover, nadroparin calcium had the highest risk of liver dysfunction, approximately 2.2 times (95% confidence interval [CI], 1.1740-4.224; P = .015) that of enoxaparin sodium. In conclusion, nearly one-fifth and 10% of patients prescribed with LMWH or fondaparinux, respectively, for pulmonary embolism had liver dysfunction, mainly with mild liver injury and characterized by self-limited elevated serum transaminase levels. Hence, during the 3 anticoagulant applications, we should pay more attention to the monitoring of liver function in the first week and transit to oral anticoagulants if possible, especially for patients who are HBsAg+ or suffering from other liver diseases.


Assuntos
Anticoagulantes/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Inibidores do Fator Xa/efeitos adversos , Fondaparinux/efeitos adversos , Heparina de Baixo Peso Molecular/efeitos adversos , Fígado/efeitos dos fármacos , Embolia Pulmonar/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/administração & dosagem , Povo Asiático , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Combinação de Medicamentos , Enoxaparina/administração & dosagem , Enoxaparina/efeitos adversos , Enoxaparina/análogos & derivados , Inibidores do Fator Xa/administração & dosagem , Feminino , Fondaparinux/administração & dosagem , Heparina de Baixo Peso Molecular/administração & dosagem , Antígenos de Superfície da Hepatite B , Humanos , Masculino , Pessoa de Meia-Idade , Nadroparina/administração & dosagem , Nadroparina/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo
7.
Pharmacology ; 105(1-2): 73-78, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31578015

RESUMO

INTRODUCTION: Critically ill patients are exposed to a high risk of developing thromboembolism. Moreover, standard prophylaxis with subcutaneous (SC) heparin is less efficient in patients requiring vasopressors. The aim is a comparison of pharmacokinetics between SC and intravenous (IV) applied nadroparin. METHODS: Thirty-eight ventilated ICU patients requiring vasopressor support were randomized into a single dose of nadroparin 3,800 IU (0.4 mL) subcutaneously (SC group) or 1,900 IU (0.2 mL) intravenously (IV group). Anti-factor Xa activity (anti-Xa) was observed over 24 h; data are stated as median (IQR). RESULTS: Peak anti-Xa was significantly higher in the IV group 0.42 (0.39-0.43) IU/mL than in the SC group 0.16 (0.09-0.18) IU/mL (p < 0.001). There was a trend towards higher area under the curve (AUC) of anti-Xa in the SC group 1.41 (0.41-1.80) IU/mL × h than in the IV group 1.04 (0.93-1.13) IU/mL × h (p = 0.08). In the SC group, there was a negative correlation between anti-Xa AUC and both capillary refill time Xa (r = -0.86) and norepinephrine dose (r = -0.68). In the IV group, anti-Xa decrease half-life was 1.6 (1.4-2.0) h. CONCLUSIONS: IV administration of 1,900 IU of nadroparin led to a predictable effective peak anti-Xa. After SC administration, anti-Xa was heterogeneous and significantly influenced by peripheral perfusion.


Assuntos
Anticoagulantes/farmacocinética , Nadroparina/farmacocinética , Administração Intravenosa , Idoso , Anticoagulantes/administração & dosagem , Estado Terminal , Fator Xa/análise , Feminino , Humanos , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade , Nadroparina/administração & dosagem , Vasoconstritores/uso terapêutico , Tromboembolia Venosa/prevenção & controle
8.
Br J Surg ; 106(6): 765-773, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30776085

RESUMO

BACKGROUND: Postpancreatectomy haemorrhage (PPH) and venous thromboembolism (VTE) are serious complications following pancreatic surgery. The aim was to assess the timing, occurrence and predictors of PPH and VTE. METHODS: Elective pancreatic resections undertaken in a single university hospital between November 2013 and September 2017 were assessed. Three intervals were reviewed, each with a different routine regimen of nadroparin: 2850 units once daily (single dose) administered in hospital only, or 5700 units once daily (double dose) or 2850 units twice daily (split dose) administered in hospital and continued for 6 weeks after surgery. Clinically relevant PPH (CR-PPH) was classified according to International Study Group of Pancreatic Surgery criteria. VTE was defined according to a number of key diagnostic criteria within 6 weeks of surgery. Cox regression analyses were performed to test the hypotheses that the double-dose group would experience more PPH than the other two groups, the single-dose group would experience more VTE than the other two groups, and the split-dose group would experience the fewest adverse events (PPH or VTE). RESULTS: In total, 240 patients were included, 80 per group. The double-dose group experienced significantly more CR-PPH (hazard ratio (HR) 2·14, 95 per cent c.i. 1·16 to 3·94; P = 0·015). More relaparotomies due to CR-PPH were performed in the double-dose group (16 versus 3·8 per cent; P = 0·002). The single-dose group did not experience more VTE (HR 1·41, 0·43 to 4·62; P = 0·570). The split dose was not associated with fewer adverse events (HR 0·77, 0·41 to 1·46; P = 0·422). Double-dose low molecular weight heparin (LMWH), high BMI and pancreatic fistula were independent predictors of CR-PPH. CONCLUSION: A double dose of LMWH prophylaxis continued for 6 weeks after pancreatic resection was associated with a twofold higher rate of CR-PPH, resulting in four times more relaparotomies. Patients receiving a single daily dose of LMWH in hospital only did not experience a higher rate of VTE.


Assuntos
Anticoagulantes/administração & dosagem , Nadroparina/administração & dosagem , Pancreatectomia , Pancreaticoduodenectomia , Cuidados Pós-Operatórios/métodos , Hemorragia Pós-Operatória/prevenção & controle , Tromboembolia Venosa/prevenção & controle , Idoso , Anticoagulantes/uso terapêutico , Relação Dose-Resposta a Droga , Esquema de Medicação , Procedimentos Cirúrgicos Eletivos , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Nadroparina/uso terapêutico , Hemorragia Pós-Operatória/diagnóstico , Hemorragia Pós-Operatória/epidemiologia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/etiologia
9.
Nephrology (Carlton) ; 23(4): 317-322, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28052451

RESUMO

AIM: This study was conducted to evaluate low-molecular weight heparin (LMWH) as anticoagulation for nocturnal home haemodialysis (NHHD). While its longer half-life may cause drug accumulation in frequent dialysis, the essential need of a supplementary intra-dialytic bolus for the sleeping patients also renders LMWH's use impractical. METHODS: The recruited patients, who were on alternate-day 8 h haemodialysis, were randomized to receive either nadroparin or unfractionated heparin (UFH) for a week. They underwent crossover to receive the alternate anticoagulant in the next week. A nadroparin infusion regimen was adopted to enhance its practicability, which consisted of a loading dose of 35 IU/kg and a continuous infusion of 10 IU/kg per hour for 6 h. RESULTS: A total of 12 NHHD patients were recruited. With nadroparin infusion, the mean anti-Xa levels at the 2nd , 4th , 6th and 8th hours of dialysis were 0.46 ± 0.11, 0.55 ± 0.14, 0.61 ± 0.15 and 0.45 ± 0.15 IU/mL respectively. Comparing to UFH, which offered satisfactory anticoagulation according to the activated partial thromboplastin time, nadroparin-treated dialysis achieved similar thrombus scores and dialyser urea/creatinine clearances at the end of haemodialysis. During the post-dialysis period, one patient demonstrated residual LMWH effect (anti-Xa level 0.09 IU/mL) on the next day, whereas none had detectable anti-Xa activities 2 days afterwards upon next dialysis. CONCLUSIONS: Low-molecular weight heparin infusion is practical and effective as anticoagulation for NHHD. It can be safely used in an alternate-day haemodialysis schedule. A close monitoring for LMWH accumulation is recommended if long dialysis is performed daily.


Assuntos
Anticoagulantes/administração & dosagem , Coagulação Sanguínea/efeitos dos fármacos , Hemodiálise no Domicílio/métodos , Nadroparina/administração & dosagem , Anticoagulantes/efeitos adversos , Estudos Cross-Over , Monitoramento de Medicamentos/métodos , Feminino , Hemodiálise no Domicílio/efeitos adversos , Hong Kong , Humanos , Infusões Parenterais , Masculino , Pessoa de Meia-Idade , Nadroparina/efeitos adversos , Tempo de Tromboplastina Parcial , Fatores de Tempo , Resultado do Tratamento
11.
Acta Haematol ; 137(4): 201-206, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28478442

RESUMO

The aim of this study is to investigate thrombogenesis and the hypercoagulable changes in pregnant women affected by thrombophilia who received low-molecular-weight heparin (LWMH) prophylaxis. We included 21 pregnant women affected by thrombophilia treated with LWMH and 20 nontreated normal pregnant women as the control group. The sample group of thrombophilic pregnant women included different conditions (factor V Leiden mutation, protein C deficiency, protein S deficiency, antiphospholipid antibodies syndrome, and combined defects). Three blood samples were collected during pregnancy (i.e., at 16, 20, and 24 weeks) and tested for activated partial thromboplastin time and prothrombin fragment F1 + 2 (F1 + 2); anti-FXa activity was tested only in treated thrombophilic pregnant women. F1 + 2 levels progressively increased during pregnancy in both study groups. However, the F1 + 2 increase in women exposed to heparin prophylaxis was significantly lower than that in normal pregnant women in all 3 measurements carried out during gestation (p < 0.05); a statistically significant inverse correlation between F1 + 2 levels and anti-Xa activity (R = -0.8575, p < 0.05) was observed in treated women during pregnancy. Our findings suggest that F1 + 2 in addition to anti-Xa measurement could be used to adjust LWMH prophylaxis, at least in high-risk pregnant women.


Assuntos
Heparina de Baixo Peso Molecular/uso terapêutico , Complicações Hematológicas na Gravidez/tratamento farmacológico , Trombofilia/tratamento farmacológico , Trombose/prevenção & controle , Adulto , Anticoagulantes/administração & dosagem , Anticoagulantes/uso terapêutico , Estudos de Casos e Controles , Inibidores do Fator Xa/sangue , Feminino , Heparina de Baixo Peso Molecular/administração & dosagem , Humanos , Nadroparina/administração & dosagem , Nadroparina/uso terapêutico , Tempo de Tromboplastina Parcial , Fragmentos de Peptídeos/sangue , Projetos Piloto , Gravidez , Complicações Hematológicas na Gravidez/sangue , Protrombina , Trombofilia/sangue , Trombofilia/complicações , Trombose/sangue , Trombose/complicações
12.
J Thromb Haemost ; 15(7): 1386-1391, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28440008

RESUMO

Essentials Low-molecular-weight-heparins (LMWH) kinetics differ which may result in different bleeding risks. A cohort of 12 934 venous thrombosis patients on LMWH was followed until major bleeding. The absolute major bleeding risk was low among patients registered at the anticoagulation clinic. Once-daily dosing was associated with a lower bleeding risk as compared with twice-daily. SUMMARY: Background Low-molecular-weight heparins (LMWHs) are considered members of a class of drugs with similar anticoagulant properties. However, pharmacodynamics and pharmacokinetics between LMWHs differ, which may result in different bleeding risks. As these agents are used by many patients, small differences may lead to a large effect on numbers of major bleeding events. Objectives To determine major bleeding risks for different LMWH agents and dosing schedules. Methods A cohort of acute venous thrombosis patients from four anticoagulation clinics who used an LMWH and a vitamin K antagonist were followed until they ceased LMWH treatment or until major bleeding. Exposures were classified according to different types of LMWHs and for b.i.d. and o.d. use. Cumulative incidences for major bleeding per 1000 patients and risk ratios were calculated and adjusted for study center. Results The study comprised 12 934 patients with a mean age of 59 years; 6218 (48%) were men. The cumulative incidence of major bleeding was 2.5 per 1000 patients (95% confidence interval [CI], 1.7-3.5). Enoxaparin b.i.d. or o.d. was associated with a relative bleeding risk of 1.7 (95% CI, 0.2-17.5) compared with nadroparin o.d. In addition, a nadroparin b.i.d. dosing schedule was associated with a 2.0-fold increased major bleeding risk (95% CI, 0.8-5.1) as compared with a nadroparin o.d. dosing schedule. Conclusions Absolute major bleeding rates were low for all LMWH agents and dosing schedules in a large unselected cohort. Nevertheless, twice-daily dosing with nadroparin appeared to be associated with an increased major bleeding risk as compared with once-daily dosing, as also suggested in a meta-analysis of controlled clinical trials.


Assuntos
Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Hemorragia/diagnóstico , Heparina de Baixo Peso Molecular/administração & dosagem , Heparina de Baixo Peso Molecular/efeitos adversos , Trombose Venosa/diagnóstico , Doença Aguda , Adulto , Idoso , Estudos de Coortes , Esquema de Medicação , Feminino , Hemorragia/complicações , Heparina/efeitos adversos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Nadroparina/administração & dosagem , Nadroparina/efeitos adversos , Embolia Pulmonar/tratamento farmacológico , Risco , Resultado do Tratamento , Tromboembolia Venosa/tratamento farmacológico , Trombose Venosa/complicações , Vitamina K/antagonistas & inibidores
13.
Int J Clin Pharmacol Ther ; 55(5): 433-441, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28139973

RESUMO

OBJECTIVE: Our study is aimed to explore effects of five treatment regimens on blood loss and blood transfusion rate in total knee arthroplasty (TKA) patients. METHODS: 191 TKA patients were divided into the rivaroxaban, nadroparin, and tranexamic acid groups (n = 37 each) as well as into the affected-limb-position and tourniquet group (n = 40 each). A 3-month follow-up after operation was needed for all patients. The total blood loss, hidden blood loss, and dominant blood loss were recorded, and hemoglobin and red blood cell changes, pain and knee swelling degrees, hospital for special surgery (HSS), and American knee society (KSS) knee scores were observed. RESULTS: When compared with the rivaroxaban, nadroparin, and tourniquet groups, TKA patients' dominant blood loss, hidden blood loss, total blood loss, rate and volume of blood transfusion in the tranexamic acid and affected-limb-position groups were significantly decreased. While 7 days after operation, the hemoglobin and red blood cells in the tranexamic acid and affected-limb-position groups were significantly increased. At 1 month and 3 months after operation, when compared with the rivaroxaban, nadroparin, and tourniquet groups, the HSS and KSS scores in the tranexamic acid and affected-limb-position groups were all increased. In comparison with the rivaroxaban, nadroparin, and tourniquet groups, the D-Dimers after operation in the tranexamic acid and affected-limb-position groups were significantly lower. CONCLUSION: These results demonstrated that for TKA patients, the tranexamic acid and affected-limb-position could obviously reduce the blood loss and blood transfusion rate.
.


Assuntos
Antifibrinolíticos/administração & dosagem , Artroplastia do Joelho/efeitos adversos , Perda Sanguínea Cirúrgica/prevenção & controle , Transfusão de Sangue , Posicionamento do Paciente , Hemorragia Pós-Operatória/prevenção & controle , Ácido Tranexâmico/administração & dosagem , Idoso , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Antifibrinolíticos/efeitos adversos , Biomarcadores/sangue , China , Inibidores do Fator Xa/administração & dosagem , Inibidores do Fator Xa/efeitos adversos , Feminino , Hemoglobinas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Nadroparina/administração & dosagem , Nadroparina/efeitos adversos , Hemorragia Pós-Operatória/sangue , Hemorragia Pós-Operatória/etiologia , Rivaroxabana/administração & dosagem , Rivaroxabana/efeitos adversos , Fatores de Tempo , Torniquetes , Ácido Tranexâmico/efeitos adversos , Resultado do Tratamento
14.
Artigo em Inglês | MEDLINE | ID: mdl-27646496

RESUMO

AIMS: This study aimed to compare the efficacy and safety of heparin and nadroparin in order to provide an additional therapeutic option for patients with acute ischemic stroke in, whom systemic thrombolysis was excluded, or thrombectomy could not be performed. METHODS: We describe a prospective randomized double-blind placebo-controlled pilot study in acute ischemic stroke. The therapeutic window was between 4.5 and 24 h after the onset of stroke. During the first 24 h of treatment, the patients divided into 3 groups received placebo, heparin or nadroparin (in therapeutic doses). During the following 48 h, each patient received nadroparin in the therapeutic dose. 24 h after start of treatment they began taking 100 mg aspirin daily. The primary safety indicator was incidence of complications such as intracerebral or systemic hemorrhage, or death. Efficacy was primarily monitored by the neurological modified Rankin Scale (mRS) at 90 days. RESULTS: There were no signs of intracerebral or systemic bleeding in the cohort of 87 patients. Two patients died - one (3.7%) in the heparin and one (3.8%) in the placebo group due to causes not connected with the treatment. There was a statistically significant difference in mRS on the 90th day between the heparin and placebo groups (21 (80%) vs 13 (50%), P=0.0350) and between the nadroparin and placebo groups (29 (85%) vs 13 (50%), P=0.0031). CONCLUSION: The results show that the treatment with heparin and nadroparin is safe and effective. TRIAL REGISTRATION: Trial is registered in ClinicalTrials.gov: NCT01862978.


Assuntos
Anticoagulantes/administração & dosagem , Isquemia Encefálica/prevenção & controle , Heparina/administração & dosagem , Nadroparina/administração & dosagem , Acidente Vascular Cerebral/prevenção & controle , Administração Cutânea , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Método Duplo-Cego , Feminino , Hemorragia/induzido quimicamente , Heparina/efeitos adversos , Heparina de Baixo Peso Molecular/administração & dosagem , Heparina de Baixo Peso Molecular/efeitos adversos , Humanos , Infusões Intravenosas , Masculino , Nadroparina/efeitos adversos , Projetos Piloto , Estudos Prospectivos , Resultado do Tratamento
15.
Oncol Rep ; 36(4): 2200-6, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27498922

RESUMO

Low-molecular-weight heparins (LMWHs), which are commonly used in venous thromboprophylaxis and treatment, have recently been reported to have effects on cancer metastasis in pre-clinical research studies. This study was planned to define the synergistic antitumor effects of nadroparin (a kind of LMWH) combined with radiotherapy in A549 cells. Six experimental groups were set up in our study according to the different treatment: control group; irradiation (IR) group; low dose of nadroparin group (LMWH50, L50); high dose of nadroparin group (LMWH100, L100); LMWH50+IR group; LMWH100+IR group. The viability of A549 cells was assessed by Cell Counting Kit-8 (CCK-8) assay. The apoptosis of tumor cells was analyzed by flow cytometry (FCM) after treatment. The concentration of transforming growth factor-ß1 (TGF-ß1) in the culture supernatants was measured by enzyme-linked immunosorbent assay (ELISA). The migration and invasion of the A549 cells were tested by the Transwell chamber assay. The expression of survivin, CD147 and matrix metalloproteinase-2 (MMP-2) was analyzed by western blotting. CCK-8 assay showed that irradiation or nadroparin alone slightly inhibited the cell viability while the combined treatments significantly inhibited the cell viability in a dose- and time-dependent manner. The apoptosis rate showed greater improvement dose- and time­dependently in the groups receiving combination therapy of nadroparin and irradiation than the control group or the group receiving nadroparin or irradiation alone by FCM. ELISA assay showed that the decreased TGF-ß1 secretion was found after combined treatments with nadroparin and irradiation compared to either treatment alone. The Transwell chamber assay showed that nadroparin not only significantly suppressed the migration and invasion of A549 cells but also inhibited the enhanced ability of migration and invasion induced by X-ray irradiation. Western blotting showed that nadroparin inhibited the upregulated effects of survivin and MMP-2 expression induced by radiation in the combined treatment groups in a dose- and time-dependent manner. Moreover, the expression level of CD147 was the lowest in the combined treatment groups. This study identified that combination of nadroparin and irradiation had a strong synergistic antitumor effect in a dose- and time-related manner in vitro, which was reflected in the inhibition of cell viability, invasion and metastasis, promotion of apoptosis, inhibited secretion level of TGF-ß1 and downregulation of CD147, MMP-2 and survivin expression.


Assuntos
Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/radioterapia , Basigina/biossíntese , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Metaloproteinase 2 da Matriz/genética , Fator de Crescimento Transformador beta1/biossíntese , Células A549 , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Basigina/genética , Movimento Celular/efeitos dos fármacos , Movimento Celular/efeitos da radiação , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Metaloproteinase 2 da Matriz/biossíntese , Nadroparina/administração & dosagem , Invasividade Neoplásica/genética , Fosforilação , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/efeitos da radiação , Fator de Crescimento Transformador beta1/genética
16.
Acta Clin Croat ; 55(3): 414-421, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-29045105

RESUMO

Fondaparinux has been shown to be as effective as low molecular weight heparin in orthopedic surgery, with no cases of heparin induced thrombocytopenia proven until today. The main goal of this prospective randomized controlled trial was to define whether thromboprophylaxis in patients with primary osteoarthritis of the knee undergoing total knee arthroplasty (TKA) influences clinical parameters in the same manner in patients receiving fondaparinux as in those receiving nadroparin during the first 7 postoperative days. Sixty patients with primary knee osteoarthritis underwent unilateral TKA performed by the same surgeon and were randomized into two groups of 30 patients receiving either fondaparinux or nadroparin thromboprophylaxis. Patients were compared according to the duration of operation, perioperative blood loss, laboratory results and clinical evaluation of the edema during the early postoperative period. No differences were found between the groups in the mean duration of surgery, perioperative blood loss, and most of laboratory results. The level of urea was significantly lower in the nadroparin group on the first and second postoperative day. No cases of heparin induced thrombocytopenia, deep vein thrombosis or pulmonary embolism were noted during the study. Study results showed both fondaparinux and nadroparin to have the same influence on clinical parameters during the first 7 postoperative days in patients undergoing TKA.


Assuntos
Anticoagulantes/uso terapêutico , Artroplastia do Joelho/efeitos adversos , Inibidores do Fator Xa/administração & dosagem , Nadroparina/administração & dosagem , Polissacarídeos/administração & dosagem , Tromboembolia Venosa/prevenção & controle , Adulto , Feminino , Fondaparinux , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/cirurgia , Complicações Pós-Operatórias/prevenção & controle , Estudos Prospectivos
17.
Neth J Med ; 73(8): 373-8, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26478547

RESUMO

BACKGROUND: Low-molecular-weight heparins (LMWHs) have been shown to accumulate in patients with renal insufficiency, especially in therapeutic dosages. Although no appropriate studies have been conducted for prophylactic dosages of nadroparin, dose reduction is sometimes recommended, especially for high prophylactic dosages. We assessed accumulation of a prophylactic dose of 5700 IU subcutaneous nadroparin once daily in patients with renal insufficiency. METHODS: We conducted a prospective cohort study and measured peak anti-Xa activity four hours after subcutaneous nadroparin injection on day 1, 3, 5 and if possible day 10 in adults with and without renal insufficiency defined as a glomerular filtration rate (GFR) below or above 50 ml/min/1.73 m2. Patients with a GFR below 10 ml/min/1.73 m2 were excluded. RESULTS: We included 14 patients in each group. In the group with renal failure 12 patients had a GFR between 30 and 50 ml/min/1.73 m2. Peak anti-Xa activity showed a high interindividual variability, but was fairly constant within each patient. There was no rise in peak anti-Xa activity on day 3 and 5 after consecutive administration. In the group with normal renal function, peak anti-Xa activity declined on day 5 compared with day 1 (p = 0.005). CONCLUSION: Prophylactic dosages of nadroparin showed no accumulation in patients with a GFR between 30-50 ml/min/1.73 m2. Dose reduction in this group could lead to suboptimal thromboprophylaxis. Due to underrepresentation of patients with a GFR < 30 ml/min/1.73 m2 (n = 2), we cannot give recommendations for this group.


Assuntos
Anticoagulantes/farmacocinética , Nadroparina/farmacocinética , Insuficiência Renal/metabolismo , Tromboembolia Venosa/prevenção & controle , Idoso , Anticoagulantes/administração & dosagem , Inibidores do Fator Xa , Feminino , Humanos , Injeções Subcutâneas , Masculino , Nadroparina/administração & dosagem , Estudos Prospectivos
18.
Neth J Med ; 73(6): 270-5, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26228191

RESUMO

BACKGROUND: Low-molecular-weight heparins (LMWHs) are increasingly used as anticoagulant during haemodialysis. The aim of this study is to establish the efficiency and duration of anticoagulation with dalteparin and nadroparin administration in patients treated with nocturnal haemodialysis. METHODS: All patients were treated with nocturnal in-centre haemodialysis, 3-4 times a week. Anticoagulation was obtained with dalteparin (n = 15) or nadroparin (n = 10). Anti-factor- Xa activity was measured during a midweek dialysis session at t = 0, 4 and 8 hours. RESULTS: The LMWH dose necessary to prevent extracorporeal circuit clotting was higher for dalteparin than for nadroparin. In the dalteparin group, anti-Xa activity was almost negligible at the start of dialysis whereas most patients on nadroparin still had anti-Xa activity at the start of dialysis (0.08 (IQR 0.05-0.11) IU÷ml), reflecting the effect of previous LMWH administration. After eight hours of dialysis, median anti-factor-Xa activity was 0.49 (IQR 0.22-0.57) after dalteparin and 0.69 (IQR 0.55- .83) after nadroparin (p = 0.01). When a target range of 0.2-0.6 IU÷ml was applied, the present dosing method led to over-anticoagulation in more than half of the patients. CONCLUSION: Administration of two doses of LMWH is an effective method of anticoagulation in nocturnal, eight-hour haemodialysis. With two doses of dalteparin, a larger proportion of patients reached but did not exceed target levels of anticoagulation, compared with two doses of nadroparin. Nadroparin caused prolonged anti-Xa activity with measurable anticoagulation up to the next dialysis session. The measurement of anti-Xa activity is advocated for dose assessment of LMWH, when LMWH is used as anticoagulant during nocturnal haemodialysis.


Assuntos
Oclusão de Enxerto Vascular/prevenção & controle , Falência Renal Crônica/terapia , Nadroparina/administração & dosagem , Diálise Renal , Anticoagulantes/administração & dosagem , Coagulação Sanguínea/efeitos dos fármacos , Dalteparina/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Oclusão de Enxerto Vascular/sangue , Humanos , Falência Renal Crônica/sangue , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
19.
Hamostaseologie ; 35(4): 358-63, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26194889

RESUMO

UNLABELLED: Deep-vein thrombosis and subsequent pulmonary embolism are major complications in total joint arthroplasty of the lower limbs. New oral anticoagulants are increasingly prescribed as thromboprophylaxis due to their simple administration and encouraging phase III marketing studies. PATIENTS, METHODS: In this observational study, we compared the efficacy and safety of rivaroxaban with nadroparin in 1302 unselected patients receiving hip or knee arthroplasty. RESULTS: Venous thrombembolism occurred in 3.3% (2.3%; 4.7%, 95% CI, n = 838) of patients receiving rivaroxaban and in 4.3% (2.7%; 6.7%, 95% CI, n = 464) of patients receiving nadroparin resulting in an absolute risk reduction (ARR) of 1.0% (-1.4%; 3.3%, 95% CI). CONCLUSIONS: With an odds ratio of 0.6 (0.4; 1.0, 95% CI), rivaroxaban was associated with a decreased perioperative drop in haemoglobin exhibiting an improved thromboprophylactic profile when compared to high dose nadroparin. Furthermore, transfusion rates were 8.8% (-2.7%; 19.9%, 95% CI) lower in patients receiving rivaroxaban. However, as previous studies have shown, low preoperative haemoglobin remains the most predictive factor for postoperative transfusions (OR: 2.4 [1.3; 4.4, 95% CI]).


Assuntos
Artroplastia de Quadril/mortalidade , Artroplastia do Joelho/mortalidade , Nadroparina/administração & dosagem , Rivaroxabana/administração & dosagem , Tromboembolia Venosa/mortalidade , Tromboembolia Venosa/prevenção & controle , Artroplastia de Quadril/estatística & dados numéricos , Artroplastia do Joelho/estatística & dados numéricos , Causalidade , Relação Dose-Resposta a Droga , Inibidores do Fator Xa/administração & dosagem , Feminino , Fibrinolíticos/administração & dosagem , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/prevenção & controle , Prevalência , Fatores de Risco , Taxa de Sobrevida , Resultado do Tratamento , Tromboembolia Venosa/diagnóstico
20.
Tumour Biol ; 36(6): 4689-97, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25619477

RESUMO

Low molecular weight heparin (LMWH) improving the cancer survival has been attracting attention for many years. Our previous study found that LMWH (Fraxiparine) strongly downregulated the invasive, migratory, and adhesive ability of human lung adenocarcinoma A549 cells. Here, we aimed to further identify the antitumor effects and possible mechanisms of Fraxiparine on A549 cells and human highly metastatic lung cancer 95D cells. The ability of cell invasion, migration, and adhesion were measured by Transwell, Millicell, and MTT assays. FITC-labeled phalloidin was used to detect F-actin bundles in cells. Chemotactic migration was analyzed in a modified Transwell assay. Measurement of protein expression and phosphorylation activity of PI3K, Akt, and mTOR was performed with Western blot. Our studies found that Fraxiparine significantly inhibited the invasive, migratory, and adhesive characteristics of A549 and 95D cells after 24 h incubation and showed a dose-dependent manner. Fraxiparine influenced the actin cytoskeleton rearrangement of A549 and 95D cells by preventing F-actin polymerization. Moreover, Fraxiparine could significantly inhibit CXCL12-mediated chemotactic migration of A549 and 95D cells in a concentration-dependent manner. Furthermore, Fraxiparine might destroy the interaction between CXCL12-CXCR4 axis, then suppress the PI3K-Akt-mTOR signaling pathway in lung cancer cells. For the first time, our data indicated that Fraxiparine could significantly inhibit the motility of lung cancer cells by restraining the actin cytoskeleton reorganization, and its related mechanism might be through inhibiting PI3K-Akt-mTOR signaling pathway mediated by CXCL12-CXCR4 axis. Therefore, Fraxiparine would be a potential drug for lung cancer metastasis therapy.


Assuntos
Adenocarcinoma/genética , Movimento Celular/efeitos dos fármacos , Quimiocina CXCL12/biossíntese , Neoplasias Pulmonares/genética , Nadroparina/administração & dosagem , Receptores CXCR4/biossíntese , Citoesqueleto de Actina/efeitos dos fármacos , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão , Animais , Adesão Celular/efeitos dos fármacos , Quimiocina CXCL12/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Camundongos , Invasividade Neoplásica/genética , Fosfatidilinositol 3-Quinases/genética , Fosforilação , Proteínas Proto-Oncogênicas c-akt/genética , Receptores CXCR4/genética , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/genética , Ensaios Antitumorais Modelo de Xenoenxerto
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