RESUMO
BACKGROUND: LY517717 is an oral direct inhibitor of activated factor X that is currently under clinical development. OBJECTIVES: The aims of this proof-of-concept study in patients undergoing total knee replacement (TKR) or total hip replacement (THR) were to determine whether LY517717 can safely reduce the risk of venous thromboembolism (VTE) and to identify at least one dose of LY517717 that is non-inferior to enoxaparin. METHODS: In a double-blind, parallel-arm, dose-ranging study, patients undergoing TKR or THR were randomly allocated to receive once-daily oral LY517717 (25, 50, 75, 100, 125 or 150 mg), started 6-8 h after wound closure, or s.c. enoxaparin, 40 mg, started in the evening before surgery. The primary efficacy endpoint was the composite of deep venous thrombosis (DVT), detected by mandatory bilateral venography performed at the end of the study treatment (between days 5 and 9), and objectively confirmed symptomatic DVT and/or pulmonary embolism (PE), occurring during the treatment period. The combination of major and minor bleeding was the primary safety endpoint. RESULTS: Five hundred and seven patients received at least one dose of LY517717 or enoxaparin (safety population). Three hundred and ninety-one patients had evaluable bilateral venography or experienced a clinical DVT and/or PE (primary efficacy population). LY517717 treatment resulted in a dose-dependent decrease in the incidence of thromboembolic events (P = 0.0001). The incidences of VTE with 100, 125, and 150 mg of LY517717 were 19%, 19% and 16%, respectively, compared to 21% with enoxaparin. The efficacies of 100-mg, 125-mg and 150-mg doses of LY517717 were non-inferior to that of enoxaparin according to prespecified criteria. Bleeding events were uncommon in both LY517717 and enoxaparin patients. CONCLUSIONS: Doses of 100, 125 and 150 mg of LY517717 are non-inferior to enoxaparin for the prevention of VTE after TKR or THR, and are associated with similar low rates of bleeding.
Assuntos
Artroplastia de Quadril/efeitos adversos , Artroplastia do Joelho/efeitos adversos , Inibidores do Fator Xa , Glicina/análogos & derivados , Piperazinas/farmacologia , Complicações Pós-Operatórias , Tromboembolia/prevenção & controle , Trombose Venosa/prevenção & controle , Adulto , Idoso , Relação Dose-Resposta a Droga , Feminino , Glicina/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade , Tromboembolia/etiologia , Resultado do Tratamento , Trombose Venosa/etiologiaRESUMO
Essentials Coronary artery bypass graft (CABG) failure is associated with myocardial infarction and death. We tested whether more frequent dosing improves aspirin (ASA) response following CABG surgery. Twice-daily compared with once-daily dosing reduces ASA hyporesponsiveness after CABG surgery. The efficacy of twice-daily ASA needs to be tested in a trial powered for clinical outcomes. SUMMARY: Background Acetyl-salicylic acid (ASA) hyporesponsiveness occurs transiently after coronary artery bypass graft (CABG) surgery and may compromise the effectiveness of ASA in reducing thrombotic graft failure. A reduced response to ASA 81 mg once-daily after CABG surgery is overcome by four times daily ASA dosing. Objectives To determine whether ASA 325 mg once-daily or 162 mg twice-daily overcomes a reduced response to ASA 81 mg once-daily after CABG surgery. Methods Adults undergoing CABG surgery were randomized to ASA 81 mg once-daily, 325 mg once-daily or 162 mg twice-daily. The primary outcome was median serum thromboxane B2 (TXB2 ) level on postoperative day 4. We pooled the results with those of our earlier study to obtain better estimates of the effect of ASA 325 mg once-daily or in divided doses over 24 h. Results We randomized 68 patients undergoing CABG surgery. On postoperative day 4, patients randomized to receive ASA 81 mg once-daily had a median day 4 TXB2 level of 4.2 ng mL-1 (Q1, Q3: 1.5, 7.5 ng mL-1 ), which was higher than in those randomized to ASA 162 mg twice-daily (1.1 ng mL-1 ; Q1, Q3: 0.7, 2.7 ng mL-1 ) and similar to those randomized to ASA 325 mg once-daily (1.9 ng mL-1 ; Q1, Q3: 0.9, 4.7 ng mL-1 ). Pooled data showed that the median TXB2 level on day 4 in groups receiving ASA 162 mg twice-daily or 81 mg four times daily was 1.1 ng mL-1 compared with 2.2 ng mL-1 in those receiving ASA 325 mg once-daily. Conclusions Multiple daily dosing of ASA is more effective than ASA 81 mg once-daily or 325 mg once-daily at suppressing serum TXB2 formation after CABG surgery. A twice-daily treatment regimen needs to be tested in a clinical outcome study.
Assuntos
Aspirina/administração & dosagem , Plaquetas/efeitos dos fármacos , Ponte de Artéria Coronária , Inibidores da Agregação Plaquetária/administração & dosagem , Idoso , Aspirina/efeitos adversos , Biomarcadores/sangue , Plaquetas/metabolismo , Ponte de Artéria Coronária/efeitos adversos , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ontário , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/efeitos adversos , Testes de Função Plaquetária , Tromboxano B2/sangue , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Upper extremity deep vein thrombosis (UEDVT) is uncommon and is associated with well-defined risk factors in the general population. Increasingly, UEDVTs are being reported during pregnancy, particularly those achieved with the use of assisted reproductive techniques (ART), and in conjunction with ovarian hyperstimulation syndrome (OHSS). AIM: We performed this review was to estimate the incidence of UEDVT associated with ART, to examine the risk factors and presentation of UEDVT in pregnancy, and to determine if differences exist between this cohort and the general population. RESULTS: There were 35 published case reports of UEDVT in pregnant women. The incidence of this condition is estimated to be 0.08-0.11% of treatment cycles in women undergoing ART. The development of UEDVT is not always be preceded by OHSS. In addition, commonly associated risk factors for UEDVT were not often reported for UEDVT that developed during pregnancy. Instead the association of UEDVT and ART was common. UEDVT in pregnancy also appears to involve the internal jugular vein more often than the subclavian vein. The reported risk of thrombus extension in this cohort, despite anticoagulation therapy, is also disconcerting. CONCLUSION: Because UEDVT may not be a rare entity during pregnancy in association with the use of ART, clinicians should be better informed of its presentation and clinical course in these women. Once UEDVT develops, appropriate therapeutic anticoagulation should be instituted and patient carefully monitored. The long-term implications and recurrence rate of this condition in pregnancy warrants further prospective studies.
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Complicações Cardiovasculares na Gravidez , Técnicas de Reprodução Assistida , Extremidade Superior/irrigação sanguínea , Trombose Venosa/diagnóstico , Trombose Venosa/terapia , Feminino , Humanos , Incidência , Síndrome de Hiperestimulação Ovariana/complicações , Gravidez , Resultado da Gravidez , Trombose Venosa/complicaçõesRESUMO
INTRODUCTION: Diagnosing deep vein thrombosis (DVT) and pulmonary embolism (PE) in pregnancy is challenging. Many of the common diagnostic tests, including compression ultrasonography (CUS), ventilation-perfusion scintigraphy (VQ scan) and helical computed tomography (hCT) that have been extensively investigated in non-pregnant patients, have not been appropriately validated in pregnancy. Extrapolating results of diagnostic studies of DVT and PE in non-pregnant patients to those who are pregnant may not be correct because during pregnancy, physiologic and anatomic changes may affect diagnostic test results, presentation and natural history of VTE. METHODS: We performed a systematic analysis of published studies addressing accurate diagnostic testing for DVT and PE in pregnancy to determine the accuracy of these tests in pregnancy. RESULTS: Our initial search yielded 530 articles of which four remained for inclusion, three studies investigating diagnostic testing in patients with a clinical suspicion of DVT or PE and one study in patients with a clinical suspicion of PE. CONCLUSIONS: From our systematic analysis of published studies investigating diagnostic testing for a clinical suspicion of DVT in pregnancy we conclude that; (i) two studies support withholding anticoagulant therapy in pregnant women with a clinical suspicion of DVT and normal results on serial IPG (impedance plethysmography), however, IPG is no longer used; (ii) one study demonstrated that a normal CUS at presentation combined with a normal D-dimer test or an abnormal D-dimer test combined with normal serial CUS appears promising for safely excluding DVT in pregnant patients, but too few patients were included in this pilot-study to draw firm conclusions; and (iii) one study investigated pregnant patients with a clinical suspicion of PE and this study concluded that in patients with normal or non-diagnostic VQ scans, withholding anticoagulant therapy might be safe, but this needs confirmation in larger studies. Recommendations on diagnostic testing of pregnant patients with a clinically suspected DVT or PE are provided.
Assuntos
Complicações Cardiovasculares na Gravidez/diagnóstico , Embolia Pulmonar/diagnóstico , Trombose Venosa/diagnóstico , Feminino , Humanos , Guias de Prática Clínica como Assunto , Gravidez , Tomografia Computadorizada Espiral , Ultrassonografia/métodos , Relação Ventilação-PerfusãoRESUMO
BACKGROUND: The rate of recurrent venous thromboembolism (VTE) in patients with a first unprovoked VTE who had a negative qualitative D-dimer test one month after stopping anticoagulant therapy was higher than expected in the D-dimer Optimal Duration Study (DODS). OBJECTIVES: To determine whether quantitative D-dimer levels using a low threshold, age- and sex-specific thresholds, or repeated measurements, would improve identification of patients at low risk of recurrent VTE. MATERIALS AND METHODS: D-dimer levels were quantified in banked samples from 307 patients in DODS who had a negative qualitative D-dimer test while on, and 1month after stopping, anticoagulant therapy and the rates of recurrent VTE were determined in patients with D-dimer levels below various predefined thresholds. RESULTS: The rate (per patient year) of recurrent VTE was: 5.9% with D-dimer levels<250µg/l at one month; 5.2% with D-dimer levels between 250 and 499µg/l at one month; 5.0% with D-dimer levels less than predefined age- and sex-specific thresholds at one month; and 6.3% when D-dimer levels were <500µg/l at both one and 7months after stopping anticoagulant therapy. These rates are similar to the overall event rate of 6.3% in patients who stopped treatment. CONCLUSIONS: Among unprovoked VTE patients who had a negative qualitative D-dimer test during and after anticoagulant therapy, low D-dimer thresholds, age and sex-adjusted thresholds or repeated measurements, did not identify subgroups with a very low rate of recurrence.
Assuntos
Anticoagulantes/uso terapêutico , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Tromboembolia Venosa/tratamento farmacológico , Estudos de Coortes , Feminino , Humanos , Masculino , Prognóstico , Recidiva , Medição de Risco , Fatores de RiscoRESUMO
Twenty-two patients with malignant pericardial effusion were seen at the Toronto General Hospital between 1979 and 1984. Under ECG monitoring, an indwelling Kifa catheter was inserted into the pericardial sac and then connected to a Hemovac system and allowed to drain for 12 to 24 hours. Xylocaine hydrochloride, 100 mg, was first instilled intrapericardially, followed by tetracycline hydrochloride, 500 to 1,000 mg, dissolved in 20 mL normal saline. The catheter was clamped for one to two hours and then allowed to drain into the Hemovac. This procedure was repeated every 24 to 48 hours until the net drainage was less than 25 mL/24 hours. Nine men and 13 women were treated (median age, 55 years). The primary malignancy included lung in 15 patients, breast in two patients, and carcinoma of the stomach, ovary, pleural mesothelioma, chronic granulocytic leukemia, and adenocarcinoma of unknown primary in one patient each. Twenty patients received one to five instillations of tetracycline. In one patient the catheter could not be inserted into the pericardial sac, and in one patient the catheter clotted before tetracycline instillation. Minor complications included transient arrhythmia in two patients, postinjection pain in four patients, and self-limited temperature elevation greater than 38.5 degrees C in two patients. fifteen patients had good control of their malignant pericardial effusion for more than 30 days (median survival, 160 days; range, 38 to 275 days). Three patients died before 30 days without evidence of effusion, and no patient surviving longer than 30 days developed recurrent effusion or pericardial constriction. Intrapericardial tetracycline instillation is a safe and efficacious treatment for malignant pericardial effusion and should be considered the first treatment modality in this situation.
Assuntos
Derrame Pericárdico/tratamento farmacológico , Tetraciclina/administração & dosagem , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cateterismo Cardíaco/efeitos adversos , Drenagem/métodos , Ecocardiografia , Eletrocardiografia , Feminino , Neoplasias Cardíacas/patologia , Neoplasias Cardíacas/secundário , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Neoplasias/radioterapia , Derrame Pericárdico/diagnóstico , Derrame Pericárdico/patologia , Pericárdio/efeitos dos fármacos , Pericárdio/patologia , Prognóstico , Esclerose , Tetraciclina/uso terapêuticoRESUMO
BACKGROUND: Although hormone replacement therapy (HRT) is associated with an increased risk of deep vein thrombosis (DVT), it is not clear if the risk differs in users of combined estrogen-progestin HRT and estrogen-only HRT. METHODS: We prospectively studied postmenopausal women with suspected DVT in whom HRT use status was ascertained and who subsequently had objective diagnostic testing to confirm or exclude DVT. Cases were patients with idiopathic DVT, in whom there were no DVT risk factors, and controls were patients without DVT, in whom there were also no DVT risk factors. The risk of DVT was determined in users of estrogen-progestin HRT and estrogen-only HRT by comparing the prevalence of current HRT use in cases with idiopathic DVT and controls without DVT (reference group). Multivariable regression analysis was done to adjust for factors that might confound an association between HRT use and the risk of DVT. RESULTS: One thousand one hundred and sixty-eight postmenopausal women with suspected DVT were assessed, from whom 95 cases of idiopathic DVT and 610 controls without DVT and no DVT risk factors were identified. Estrogen-only HRT was associated with an increased risk for DVT that was not statistically significant [odds ratio (OR) = 1.22; 95% confidence interval (CI) 0.57, 2.61]. Estrogen-progestin HRT was associated with a greater than 2-fold increased risk for DVT (OR = 2.70; 95% CI 1.44, 5.07). CONCLUSION: The risk of developing DVT may be higher in users of combined estrogen-progestin HRT than in users of estrogen-only HRT.
Assuntos
Terapia de Reposição de Estrogênios/efeitos adversos , Trombose Venosa/etiologia , Idoso , Índice de Massa Corporal , Estudos de Casos e Controles , Estrogênios/efeitos adversos , Feminino , Humanos , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Pós-Menopausa , Progestinas/efeitos adversos , Estudos Prospectivos , Risco , Fatores de RiscoRESUMO
BACKGROUND: The post-thrombotic syndrome is a chronic, poorly understood complication of deep venous thrombosis (DVT). OBJECTIVES: To evaluate predictors of the post-thrombotic syndrome, including intensity of long-term anticoagulation, and to assess the impact of the post-thrombotic syndrome on quality of life. PATIENTS AND METHODS: The setting was 13 Canadian hospitals and one US hospital. One hundred and forty-five patients with an unprovoked episode of proximal DVT who were initially treated with 3 months of conventional-intensity warfarin [target International Normalized Ratio (INR) of 2.5] then participated in a trial comparing two intensities of long-term warfarin therapy (target INR 2.5 vs. INR 1.7). Post-thrombotic syndrome was assessed at the end of the trial using a validated clinical scale. Generic and venous disease-specific quality of life was compared in patients with and without the post-thrombotic syndrome. Multivariable regression analyses were performed to identify predictors of the post-thrombotic syndrome and of its severity. RESULTS: After an average follow-up of 2.2 years, the prevalence of post-thrombotic syndrome was 37% and of severe post-thrombotic syndrome was 4%. Quality of life was worse in patients with the post-thrombotic syndrome compared with patients who did not have it. The presence of factor (F)V Leiden or the prothrombin gene mutation was an independent predictor of both a lower risk (P = 0.006) and reduced severity (P = 0.045) of the post-thrombotic syndrome. Intensity of anticoagulation did not influence the risk of developing the post-thrombotic syndrome. CONCLUSIONS: The post-thrombotic syndrome is a frequent and burdensome complication of proximal DVT, even among patients maintained on long-term oral anticoagulation. While the presence of FV Leiden or prothrombin gene mutation appears to be associated with a reduced risk of post-thrombotic syndrome, this finding requires further evaluation in prospective studies.
Assuntos
Síndrome Pós-Flebítica/diagnóstico , Trombose Venosa/complicações , Trombose Venosa/terapia , Administração Oral , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/uso terapêutico , Canadá , Fator V/genética , Feminino , Humanos , Coeficiente Internacional Normatizado , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Mutação , Prevalência , Protrombina/genética , Qualidade de Vida , Risco , Fatores de Tempo , Estados Unidos , Varfarina/uso terapêuticoRESUMO
BACKGROUND: The management of women with prosthetic heart valves during pregnancy poses a particular challenge as there are no available controlled clinical trials to provide guidelines for effective antithrombotic therapy. Oral anticoagulants such as warfarin sodium cause fetal embryopathy; subcutaneous administration of heparin sodium has been reported to be ineffective in preventing thromboembolic complications. OBJECTIVE: To identify the risks of maternal and fetal complications in women with mechanical heart valves treated with different anticoagulation regimens during pregnancy. METHODS: We performed a systematic review of the literature to determine pooled estimates of maternal and fetal risks associated with the 3 commonly used approaches: (1) oral anticoagulants (OA) throughout pregnancy, (2) replacing OA with heparin in the first trimester (from 6-12 weeks' gestation), and (3) heparin use throughout pregnancy. Fetal outcomes included spontaneous abortions and fetopathic effects, and maternal outcomes were major bleeding, thromboembolic complications, and death. RESULTS: The use of OA throughout pregnancy is associated with warfarin embryopathy in 6.4% (95% confidence interval [CI], 4.6%-8.9%) of livebirths. The substitution of heparin at or prior to 6 weeks, and continued until 12 weeks, eliminated this risk. Overall risks for fetal wastage (spontaneous abortion, stillbirths, and neonatal deaths) were similar in women treated with OA throughout, compared with women treated with heparin in the first trimester. Maternal mortality was 2.9% (95% CI, 1.9%-4.2%). Maj or bleeding events occurred in 2.5% (95% CI, 1.7%-3.5%) of all pregnancies, most at the time of delivery. The regimen associated with the lowest risk of valve thrombosis (3.9%; 95% CI, 2.9-5.9%) was the use of OA throughout; using heparin only between 6 and 12 weeks' gestation was associated with an increased risk of valve thrombosis (9.2%; 95% CI, 5.9%-13.9%). CONCLUSIONS: Thromboembolic prophylaxis of women with mechanical heart valves during pregnancy is best achieved with OA; however, this increases the risk of fetal embryopathy. Substituting OA with heparin between 6 and 12 weeks reduces the risk of fetopathic effects, but with an increased risk of thromboembolic complications. The use of low-dose heparin is definitely inadequate; the use of adjusted-dose heparin warrants aggressive monitoring and appropriate dose adjustment. Large prospective trials to determine the best regimen for these women are needed.
Assuntos
Anticoagulantes/administração & dosagem , Próteses Valvulares Cardíacas , Complicações Cardiovasculares na Gravidez/tratamento farmacológico , Tromboembolia/prevenção & controle , Administração Oral , Feminino , Heparina/administração & dosagem , Humanos , Injeções Subcutâneas , Gravidez , Resultado da Gravidez , Fatores de Risco , Tromboembolia/mortalidade , Varfarina/administração & dosagemRESUMO
A 25-year-old primiparous woman presented at 30 weeks of gestation with suspected deep vein thrombosis of the left leg. Results of initial noninvasive tests were not in agreement and subsequent venographic findings revealed left iliac vein thrombosis. Treatment was initiated with continuous intravenous unfractionated heparin sodium for 3 days and then switched to twice-daily subcutaneous unfractionated heparin. Unfractionated heparin, 60,000 U per 24 hours, was required to maintain the activated partial thromboplastin time within the therapeutic range, which posed problems because of large volumes of injection. Therapy with subcutaneous low-molecular-weight heparin was successfully substituted and the patient had an uncomplicated full-term deliver.
Assuntos
Heparina de Baixo Peso Molecular/uso terapêutico , Complicações Cardiovasculares na Gravidez/tratamento farmacológico , Tromboflebite/tratamento farmacológico , Adulto , Diagnóstico Diferencial , Resistência a Medicamentos , Feminino , Heparina/uso terapêutico , Heparina de Baixo Peso Molecular/administração & dosagem , Humanos , Injeções Subcutâneas , Tempo de Tromboplastina Parcial , Gravidez , Complicações Cardiovasculares na Gravidez/diagnóstico , Tromboflebite/diagnósticoRESUMO
The postphlebitic syndrome is a common affliction with limited therapeutic options. Patients who fail to respond to treatment with graded elastic compression stockings often develop a chronic pain syndrome manifested by intractable pain and swelling. Because lymphedema, a condition also associated with leg pain and swelling, has been successfully treated by intermittent compressive therapy with an extremity pump, we conducted a pilot study of compressive therapy in patients with severe postphlebitic syndrome. All five patients studied had dramatic improvement in symptoms and functional status without side effects. Although a large randomized trial is needed to properly evaluate compressive therapy, it appears to be very effective in selected patients.
Assuntos
Equipamentos e Provisões , Síndrome Pós-Flebítica/terapia , Adulto , Vestuário , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , PressãoRESUMO
To evaluate the reliability of two noninvasive tests, the photoplethysmograph (PPG) and venous Doppler ultrasound, in determining the presence or absence of previous proximal deep vein thrombosis (DVT), we performed a blinded retrospective cohort study of patients with objectively confirmed (DVT+) or refuted (DVT-) previous episodes of suspected DVT. Twenty-nine of 33 DVT+ patients had abnormal PPG and/or reflux by venous Doppler ultrasound, whereas 39 of 49 DVT- patients had normal PPG and no Doppler reflux (sensitivity, 88%; specificity, 80%). Of 33 DVT+ patients, 20 had abnormal Doppler results (sensitivity, 61%), in contrast to 46 of 49 DVT- patients with normal results (specificity, 94%). Moreover, 23 of 33 DVT+ patients showed abnormal PPG results (sensitivity, 70%), whereas 40 of 49 DVT- patients had normal PPG (specificity, 82%). Based on our findings, the presence of Doppler reflux is specific for previous proximal DVT, whereas a combination of normal PPG and Doppler ultrasound is reliable for excluding previous proximal DVT. Abnormal PPG with normal Doppler ultrasound does not reliably predict the presence or absence of previous DVT. However, this occurred in only 16 of 82 patients. Therefore, the combination of PPG and venous Doppler ultrasound can reliably predict the presence or absence of previous proximal DVT in most patients.
Assuntos
Pletismografia/métodos , Tromboembolia/diagnóstico , Ultrassonografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos RetrospectivosRESUMO
BACKGROUND: It is unknown whether the true risk of recurrent venous thromboembolism (VTE) is increased in patients with proximal deep vein thrombosis who are treated with continuous intravenous heparin and fail to reach a therapeutic activated partial thromboplastin time (APTT) within 24 to 48 hours of initiation of treatment. METHODS: To compare the risk of recurrent VTE in patients with early subtherapeutic APTT results and those with APTT results above the lower limit of the therapeutic range, we performed a formal review of the literature. We examined all available studies that provided information on the relation between the risk of recurrent VTE and the APTT response to heparin when initiated as a bolus followed by a continuous intravenous infusion of at least 30 000 U/24 h. RESULTS: Five studies were included in the final analysis. The overall recurrence rate was 6.3% in patients whose APTT results were subtherapeutic for the first 24 to 48 hours and 7% in patients whose APTT results were above the lower limit of the therapeutic range, providing a pooled odds ratio of 0.89 with a 95% confidence interval of 0.2 to 4.0. CONCLUSIONS: In patients with VTE who are treated with a bolus of heparin followed by a continuous intravenous infusion of at least 30 000 U/24 h, no convincing evidence shows that the risk of recurrent VTE is critically dependent on achieving a therapeutic APTT result at 24 to 48 hours.
Assuntos
Heparina/administração & dosagem , Tempo de Tromboplastina Parcial , Trombose/sangue , Trombose/tratamento farmacológico , Humanos , Infusões Intravenosas , Razão de Chances , Recidiva , Risco , Tromboembolia/tratamento farmacológicoRESUMO
BACKGROUND: The activated partial thromboplastin time (APTT) is used to adjust heparin sodium dosage. However, warfarin sodium is often administered concomitantly with heparin and may also affect the APTT and, therefore, heparin dose. We performed a prospective cohort study to quantify the effect of warfarin on the APTT in patients who are being treated with heparin. METHODS: Serial assays of APTT, international normalized ratio, heparin levels, and functional levels of prothrombin (factor II) and factors VII and X were performed in 24 patients with acute venous thromboembolism who were treated with concomitant continuous intravenous heparin and warfarin. The effects of warfarin, as expressed by international normalized ratio and coagulation factor levels, on APTT were determined. RESULTS: Warfarin markedly affected APTT; for each increase of 1.0 in the international normalized ratio, the APTT increased 16 seconds (95% confidence interval, 10-22 seconds). The effects of warfarin and heparin on APTT were additive. Consequently, warfarin markedly altered the relationship between APTT and heparin levels; of the 29 blood samples with supratherapeutic APTT, 13 had a therapeutic heparin level and 10 had a subtherapeutic heparin level. CONCLUSIONS: In patients receiving concomitant heparin and warfarin therapy, APTT reflects the combined effects of both drugs. Because of the marked effect of warfarin on the APTT, decreasing heparin dose in response to a high APTT frequently results in subtherapeutic heparin levels.
Assuntos
Anticoagulantes/farmacologia , Coagulação Sanguínea/efeitos dos fármacos , Heparina/farmacologia , Varfarina/farmacologia , Humanos , Coeficiente Internacional Normatizado , Tempo de Tromboplastina Parcial , Estudos Prospectivos , Análise de RegressãoRESUMO
OBJECTIVES: To compare the efficacy and safety of unfractionated heparin (UFH) and low-molecular-weight heparins (LMWHs) and to examine current controversies in the treatment of venous thromboembolism (VTE) (ie, setting, product type, and frequency of administration). METHODS: Data were abstracted from MEDLINE, HEALTH, previous reviews, personal files, clinical experts, and conference abstracts. Randomized controlled trials of patients diagnosed with acute VTE that compared LMWHs with UFH were included. Independent duplicate assessment was done for methodological quality and data extraction. Data are reported as pooled relative risks (RRs) and 95% confidence intervals (CIs) comparing LMWHs with UFH as determined by the random effects model. RESULTS: Thirteen studies were included. There was no statistically significant difference in risk between UFH and LMWHs for recurrent VTE (RR, 0.85 [95% CI, 0.65-1.12]), pulmonary embolism (RR, 1.02 [95% CI, 0.64-1.62]), major bleeding (RR, 0.63 [95% CI, 0.37-1.05]), minor bleeding (RR, 1.18 [95% CI, 0.87-1.61]), and thrombocytopenia (RR, 0.85 [95% CI, 0.45-1.62]). There was a statistically significant difference for risk of total mortality (RR, 0.76 [95% CI, 0.59-0.98]) in favor of LMWHs. Inpatient treatment may reduce the risk of major bleeding vs outpatient therapy. Once-daily therapy is as safe and effective as twice-daily therapy when compared indirectly. Different products could not be statistically compared, but qualitative analysis shows that there are no apparent differences in efficacy and safety. CONCLUSIONS: Low-molecular-weight heparins are at least as effective as UFH in preventing recurrent VTE. It is unlikely that LMWHs are superior in the treatment of VTE, but they do show a statistically significant decrease in total mortality. No differences were seen in the development of recurrent VTE dependent on treatment setting. There were no apparent differences between once-daily and twice-daily therapy or among products. Inpatient therapy may be associated with less major bleeding; therefore, if LMWHs are given in the outpatient setting, patients should be rigorously monitored.
Assuntos
Anticoagulantes/uso terapêutico , Heparina de Baixo Peso Molecular/uso terapêutico , Heparina/uso terapêutico , Tromboembolia/tratamento farmacológico , Humanos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: Although the incidence of the postthrombotic syndrome (PTS) has been addressed in patients with symptomatic deep vein thrombosis (DVT), less information is available on the incidence in patients who develop asymptomatic DVT after major hip or knee arthroplasty. OBJECTIVES: To determine whether symptomatic PTS occurs more frequently in patients who develop DVT after hip or knee arthroplasty than those who are free of DVT and to provide an estimate of the incidence of PTS in patients who had undergone major hip or knee arthroplasty and had proximal DVT, distal (calf) DVT, or no DVT. DESIGN AND SETTING: A cross-sectional study conducted at the Hamilton Health Sciences Corporation, Hamilton, Ontario, and the Academic Medical Centre, Amsterdam, the Netherlands. SUBJECTS AND METHODS: Two hundred fifty-five subjects who had undergone major hip or knee arthroplasty 2 to 7 years previously and had routine predischarge venography showing proximal DVT (n = 25), distal DVT (n = 66), or no DVT (n = 164) were enrolled from March 1993 through December 1998. The presence of symptomatic PTS confirmed by the presence of objectively confirmed venous valvular incompetence was ascertained. RESULTS: The rates of PTS were low and not significantly different among the 3 subgroups: 1 (4.0%, 95% confidence interval [CI] = 0.1%-20.4%) of 25 patients with proximal DVT, 4 (6.1%, 95% CI = 1.7%-14.8%) of 66 patients with distal DVT, and 7 (4.3%, 95% CI = 1.7%-8.6%) of 164 patients with no DVT. CONCLUSIONS: Symptomatic PTS is an uncommon complaint after major hip or knee arthroplasty. Patients who develop postoperative proximal or distal DVT and who receive 6 to 12 weeks of anticoagulant therapy are not predisposed to PTS.
Assuntos
Artroplastia de Quadril/efeitos adversos , Artroplastia do Joelho/efeitos adversos , Síndrome Pós-Flebítica/etiologia , Trombose Venosa/complicações , Trombose Venosa/etiologia , Idoso , Estudos Transversais , Feminino , Humanos , Incidência , Masculino , Países Baixos/epidemiologia , Ontário/epidemiologia , Pletismografia , Síndrome Pós-Flebítica/diagnóstico , Síndrome Pós-Flebítica/epidemiologia , Trombose Venosa/diagnósticoRESUMO
The true maternal and fetal risks of heparin therapy during pregnancy are unknown, because most published studies are small and do not report consecutively treated patients. In order to address these issues, we performed a retrospective cohort study of 100 pregnancies in 77 women treated with heparin during pregnancy. In 98 pregnancies heparin therapy was given for the prevention or treatment of venous thromboembolism; in the remaining 2, because of prosthetic heart valves. The rates of prematurity, abortions, stillbirths, neonatal deaths, and congenital abnormalities were similar to those in the normal population. There were two bleeding episodes and no symptomatic thrombotic episodes associated with heparin therapy. We conclude that maternal heparin therapy is safe for the fetus and is associated with an acceptable bleeding rate and a low rate of thrombotic recurrence in the mother.
Assuntos
Heparina/uso terapêutico , Complicações Cardiovasculares na Gravidez/tratamento farmacológico , Anormalidades Induzidas por Medicamentos , Adulto , Estudos de Coortes , Feminino , Próteses Valvulares Cardíacas , Heparina/efeitos adversos , Humanos , Trabalho de Parto Prematuro/induzido quimicamente , Ontário , Gravidez , Resultado da Gravidez , Estudos Retrospectivos , Tromboembolia/tratamento farmacológico , Hemorragia Uterina/induzido quimicamenteRESUMO
BACKGROUND: The true incidence of postphlebitic syndrome (PPS) following proximal deep venous thrombosis (DVT) and the efficacy of graduated compression stockings in preventing and treating PPS are unknown. METHODS: A 3-part study of 202 patients evaluated 1 year after proximal DVT: 2 randomized placebo-controlled trials of stockings and 1 prospective cohort of untreated patients. Patients were evaluated for PPS, using a standardized questionnaire, and for venous valvular incompetence, using photoplethysmography and venous Doppler. They were enrolled in study 1 or study 2 if they did not have symptomatic PPS and did not have or had venous valvular incompetence, respectively, and into study 3 if they had symptomatic PPS. Study 1 patients were left untreated and followed up for development of PPS every 6 months for a mean of 55 months. Study 2 patients were randomized to a below-knee stocking (20-30 mm Hg) or a matched placebo stocking, and followed up for development of PPS every 6 months for a mean of 57 months. Study 3 patients were randomized to an active stocking (30-40 mm Hg) or a matched placebo stocking and followed up every 3 months for treatment failure, defined a priori. RESULTS: In study 1, 6 (5.0%) of 120 patients were categorized as treatment failures, a rate similar to placebo-treated study 2 patients (P =.10). In study 2, 0 (0%) of 24 active and 1 (4.3%) of 23 placebo-treated patients were categorized as treatment failures (P =.49). In study 3, 11 (61.1%) of 18 active and 10 (58.8%) of 17 placebo-treated patients were categorized as treatment failures (P>.99). CONCLUSIONS: Most patients do not have PPS 1 year after proximal DVT, and do not require stockings. We failed to show a benefit of stockings in patients with PPS, but the small numbers preclude definitive conclusions.
Assuntos
Bandagens , Síndrome Pós-Flebítica/prevenção & controle , Trombose Venosa/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome Pós-Flebítica/etiologia , Estudos Prospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Our objective was to systematically review the incidence of deep vein thrombosis (DVT) and the efficacy of thromboprophylaxis in critically ill adults, including patients admitted to intensive care units and following trauma, neurosurgery, or spinal cord injury. METHODS: Two authors independently searched MEDLINE, EMBASE, abstract databases, and the Cochrane database. Data were extracted independently in triplicate. RESULTS: Ten percent to 30% of medical and surgical intensive care unit patients develop DVT within the first week of intensive care unit admission. The use of subcutaneous low-dose heparin reduced the rate by 50% compared with no prophylaxis. Approximately 60% of trauma patients developed DVT within the first 2 weeks of admission. Use of unfractionated heparin appears to decrease the incidence of DVT by only 20%, whereas low-molecular-weight heparin decreases the incidence by a further 30%. The estimated prevalence of DVT in neurosurgical patients not given prophylaxis is 22% to 35%. Mechanical prophylaxis is efficacious, with a pooled odds ratio in 5 randomized trials of 0.28. Use of low-molecular-weight heparin has been investigated as an adjunct to mechanical prophylaxis with a pooled odds ratio of 0.59 compared with graduated compression stockings alone. The incidence of DVT without prophylaxis in acute spinal cord injury patients is likely in excess of 50% to 80%. Studies of prophylaxis in these patients are too sparse to come to any definitive conclusion. CONCLUSIONS: Critically ill patients commonly develop DVT, with rates that vary from 22% to almost 80%, depending on patient characteristics. Methods of prophylaxis proven in one group do not necessarily generalize to other critically ill patient groups. More potent prophylactic regimens other than unfractionated or low-molecular-weight heparins alone may be needed with higher-risk groups.
Assuntos
Anticoagulantes/administração & dosagem , Heparina/administração & dosagem , Trombose Venosa/epidemiologia , Trombose Venosa/prevenção & controle , Intervalos de Confiança , Estado Terminal , Relação Dose-Resposta a Droga , Feminino , Humanos , Injeções Subcutâneas , Unidades de Terapia Intensiva , Masculino , Razão de Chances , Prevalência , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de Risco , Taxa de Sobrevida , Trombose Venosa/diagnósticoRESUMO
BACKGROUND: Ventilation-perfusion (VQ) scanning is used when pulmonary embolism (PE) is suspected during pregnancy; however, the distribution of lung scan results and safety of VQ scanning have never been studied. OBJECTIVE: To study the distribution of lung scan results and safety of VQ scanning as well as the safety of withholding anticoagulation therapy following a normal or nondiagnostic scan in pregnant women. METHODS: The study group comprised 120 consecutive pregnant women who presented with suspected PE. Clinical data were collected, and the lung scans were reinterpreted by 2 independent experts. Subsequent pregnancy and pediatric outcomes were determined by direct patient follow-up. RESULTS: During the study period, 120 pregnant women (mean age, 32 years) underwent 121 VQ scans. Eight cases (6.6%) were already receiving treatment for venous thromboembolism prior to VQ scanning. In the remaining 113 scans, 83 (73.5%) were interpreted as normal, 28 (24.8%) as nondiagnostic, and 2 (1.8%) as high probability. In the 104 women who did not receive anticoagulation therapy following lung scanning (80 normal and 24 nondiagnostic), no venous thromboembolic events were reported (mean [range] length of follow-up, 20.6 [0.5-108] months). Examination of pediatric data from 110 live births (90.2%) (mean [range] age, 20.5 [0.5-100] months) revealed no increase in the rates of congenital and developmental anomalies. CONCLUSIONS: The prevalence of high-probability VQ scans in pregnant women with suspected PE and probable PE is very low. Withholding anticoagulation in pregnant women with normal or nondiagnostic VQ scans is probably safe. In addition, pediatric risks from VQ scans are low. Large prospective studies are needed to evaluate diagnostic strategies for pregnant women with suspected PE.