RESUMO
BACKGROUND: Dual-antiplatelet therapy (DAPT) is a standard strategy in acute coronary heart disease; however, it confers a considerable bleeding risk. Single-antiplatelet therapy (SAPT) inhibits haemostatic system activation ex vivo to a similar extent as DAPT. Extracellular vesicles (EV) are procoagulant and contribute to haemostatic system activation. We aimed to investigate the effect of DAPT compared with SAPT on EV. METHODS: In a randomized, double-blind, placebo-controlled trial, 44 healthy volunteers received DAPT (clopidogrelâ¯+â¯aspirin) or SAPT (clopidogrelâ¯+â¯placebo) for 7â¯days. Blood was obtained from a standardized microvascular injury and through venipuncture at baseline (BL) and at 2â¯h, 24â¯h, and 8â¯days after treatment initiation. The number, origin, and surface expression of EV were assessed using flow cytometry. Data are given as median (quartiles). Non-parametric tests were used to evaluate the short-term (BL vs 2â¯h) and long-term differences (2â¯h to 8â¯days), as well as the differences between treatment groups. RESULTS: There was no difference either in the short-term effects on the number (×103â¯mL-1) of EV in microvascular blood between DAPT [BL: 1433 (653; 3184) vs 2â¯h: 862 (545; 2026), pâ¯=â¯0.39] and SAPT [(BL: 614 (552; 1402) vs 2â¯h: 1079 (781; 1538), pâ¯=â¯0.75)] or in the long-term effects. DAPT and SAPT did not exhibit differential short-term effects on the number and proportion (36% and 27% vs 55% and 36%) of platelet-derived EV. DAPT and SAPT resulted in a significant short-term increase in phosphatidylserine expression in microvascular blood. The effects of DAPT and SAPT on EV in venous blood were similar to those in microvascular blood. CONCLUSION: DAPT and SAPT have comparable effects on the amount, origin, and surface characteristics of EV.
Assuntos
Aspirina/uso terapêutico , Clopidogrel/uso terapêutico , Vesículas Extracelulares/efeitos dos fármacos , Hemostasia/efeitos dos fármacos , Microcirculação/efeitos dos fármacos , Inibidores da Agregação Plaquetária/uso terapêutico , Adulto , Aspirina/farmacologia , Clopidogrel/farmacologia , Voluntários Saudáveis , Humanos , Masculino , Inibidores da Agregação Plaquetária/farmacologiaRESUMO
INTRODUCTION: Data on clinical characteristics and the prevalence of underlying coagulopathies in patients with mild-to-moderate bleeding disorders (MBDs) are scarce. AIM: We established the Vienna Bleeding Biobank (VIBB) to characterize and thoroughly investigate Austrian patients with MBDs. RESULTS: Four hundred eighteen patients (female = 345, 82.5%) were included. A platelet function defect (PFD) was diagnosed in 26 (6.2%) and a possible PFD in 30 (7.2%) patients. Eight patients (1.9%) were diagnosed with von Willebrand disease (VWD) (type 1 n = 6; type 2 n = 2), and 29 patients had low VWF (30-50 IU/dL). Deficiencies in factor VIII, IX, XI or XIII were found in 11 (2.6%), 3 (0.7%), 3 (0.7%) and 1 patient(s), 2 patients had dysfibrinogenaemia, and further 2 had possible PFD and FXI deficiency. Probable causal mutations were detected in 8 of 11 patients with FVIII deficiency, 2 of 3 patients with FIX deficiency and 2 of 8 patients with VWD. Three hundred three patients (72.5%) had normal results in the coagulation assays and were categorized as patients with bleeding of unknown cause (BUC). The bleeding score did not differ between patients with and without established diagnosis. A diagnosis of a bleeding disorder was more frequently made in men than in women (49.3% vs 22.9%). Male sex (OR 3.55, 95% CI: 2.02-6.22; P < .001) and blood group 0 (OR 1.86, 95% CI: 1.17-2.94; P = .008) were independently associated with diagnosis of a bleeding disorder. CONCLUSION: The high rate of patients with BUC despite in-depth haemostatic assessment underlines the incompleteness of available routine laboratory tests. Males with MBDs were more likely to be diagnosed with an established bleeding disorder than females.
Assuntos
Bancos de Espécimes Biológicos , Hemorragia/epidemiologia , Hemorragia/genética , Adulto , Áustria , Fator IX/genética , Fator VIII/genética , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Essentials Natural antibodies to oxidation-specific epitopes have antithrombotic properties. We evaluated the relation between natural IgM and IgG antibodies and the venous thrombosis risk. Risk of recurrent thrombosis was higher in patients with low natural IgM antibody levels. The protective effect of high IgM levels suggests a role of innate immune response in thrombosis. SUMMARY: Background and objectives Natural antibodies to oxidation-specific epitopes protect from atherothrombotic events. Whether mechanisms of innate immunity are relevant in the pathogenesis of venous thromboembolism (VTE) is unknown. Patients/Methods We measured plasma levels of immunoglobulin M (IgM) antibodies to oxidized low-density lipoproteins (OxLDL) and phosphocholine (PC) by enzyme linked immune assay in 663 patients with unprovoked VTE, who were prospectively followed after discontinuation of anticoagulation for a median of 8.8 years. The study endpoint was recurrent VTE. Results IgM antibody levels to OxLDL and PC were higher in patients without compared to those with recurrent VTE (n = 174, 26.2%). For each doubling of OxLDL-IgM or PC-IgM the hazard ratio (HR) of recurrence was 0.88 (95% confidence interval [CI], 0.77-1.01) and 0.82 (95% CI, 0.71-0.94), respectively. After 5 years the probability of recurrence in patients with PC-IgM levels in the highest tertile (> 19.6 RLU/100 ms) was 13.0% (95% CI, 8.1-17.6%), compared with 21.1% (95% CI, 14.9-26.9%) in the middle tertile and 20.6% (95% CI, 14.7-26.0%) in the lowest tertile. The corresponding HR was 0.56 (0.39-0.82) for PC-IgM levels in the highest compared with the lowest tertile. Neither immunoglobulin G IgG antibody levels to OxLDL nor those to PC were associated with risk of VTE. Conclusion Levels of natural IgM antibodies to oxidation-specific epitopes are inversely related to the risk of VTE.
Assuntos
Autoanticorpos/imunologia , Coagulação Sanguínea/imunologia , Epitopos , Imunidade Inata , Imunoglobulina M/imunologia , Lipoproteínas LDL/imunologia , Fosforilcolina/imunologia , Tromboembolia Venosa/imunologia , Adulto , Autoanticorpos/sangue , Biomarcadores/sangue , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Imunoglobulina M/sangue , Masculino , Pessoa de Meia-Idade , Oxirredução , Prognóstico , Estudos Prospectivos , Fatores de Proteção , Recidiva , Fatores de Risco , Fatores de Tempo , Tromboembolia Venosa/sangue , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/prevenção & controleRESUMO
Essentials Data on long-term cancer risk are controversial in patients with venous thromboembolism (VTE). We assessed long-term rates and risk factors of cancer in patients with VTE. Cancer risk after anticoagulation is not higher in VTE patients than in the general population. VTE recurrence is not predictive of a future cancer diagnosis. SUMMARY: Background Patients with venous thromboembolism (VTE) are at risk of having a subsequent cancer diagnosis. The risk is highest during the first 6 months. Reports on cancer rates thereafter are controversial. We aimed to assess long-term rates and risk factors of cancer in patients with VTE. Methods and Results We followed patients with a first unprovoked VTE after discontinuation of anticoagulation, and excluded those receiving long-term antithrombotic therapy or with major thrombophilia. The study endpoint was the occurrence of cancer. Sixty-two (5.2%) of 1188 patients developed cancer during a median follow-up of 98 months. The cumulative incidence rates of cancer were 0.7% (95% confidence interval [CI] 0.2-1.2%), 3.1% (95% CI 2.0-4.1%) and 9% (95% CI 6.5-11.5) after 1, 5 and 15 years; these were not significantly different from those in the matched general population (0.6%, 3.4%, and 12.2%, respectively). The corresponding standardized incidence ratios (ratio of the observed cancer cases and the number of cases based on national cancer incidence rates) of 1.1 (95% CI 0.5-2.5), 1.0 (95% CI 0.6-1.4) and 0.9 (95% CI 0.7-1.2) did not indicate a difference in cancer incidence between our cohort and the general population. Advancing age (hazard ratio [HR] per decade 1.5, 95% CI 1.2-2.0) and shorter duration of anticoagulation (HR per 1-month decrease 1.3, 95% CI 1.1-1.6) were associated with an increased cancer risk, whereas VTE recurrence was not (HR 1.17, 95% CI 0.66-2.07). Conclusions Asymptomatic patients with unprovoked VTE who have completed anticoagulation therapy do not have a higher cancer risk. The inverse association between the duration of anticoagulation and the incidence of cancer warrants further investigation.
Assuntos
Anticoagulantes/administração & dosagem , Neoplasias/complicações , Neoplasias/etiologia , Tromboembolia Venosa/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/uso terapêutico , Coagulação Sanguínea , Estudos de Coortes , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Recidiva , Fatores de Risco , Fatores de Tempo , Trombose Venosa/complicações , Trombose Venosa/tratamento farmacológico , Trombose Venosa/fisiopatologia , Adulto JovemAssuntos
Coagulação Sanguínea , Cardiologia/normas , Embolia Pulmonar/diagnóstico , Algoritmos , Reações Falso-Positivas , Humanos , Cooperação Internacional , Segurança do Paciente , Perfusão , Prevalência , Cintilografia , Padrões de Referência , Valores de Referência , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Sociedades MédicasRESUMO
Essentials Long-term recurrence risk of venous thromboembolism (VTE) is uncertain. We performed a prospective cohort study of 839 patients with first unprovoked VTE. VTE recurrence risk is high, particularly in men with proximal thrombosis or pulmonary embolism. Sex and VTE site determine the recurrence risk and should be considered for patient counseling. SUMMARY: Background The long-term recurrence risk (ltRR) of venous thromboembolism (VTE) is uncertain. Objective To assess the ltRR of patients with first unprovoked VTE. Patients/methods Patients were classified into three categories: distal deep vein thrombosis (DVT), proximal DVT or pulmonary embolism (PE), that is, PE associated with DVT or isolated PE. Patients with major thrombophilia or antithrombotic therapy were excluded. The endpoint was recurrent symptomatic VTE. Results A total of 839 patients were followed for a median of 7.7 years. VTE recurred in 263 patients (31%). After 10 and 20 years, the cumulative ltRR was 32% (95% confidence interval [CI], 29-36) and 44% (95% CI, 38-49) with 3.9 (95% CI, 3.3-4.6) and 3.3 (95% CI, 2.7-4.0) events per 100 patient-years, respectively. The adjusted hazard ratio was 2.1 (95% CI, 1.4-3.2) and 2.1 (95% CI, 1.4-3.2) for patients with proximal DVT or PE compared with patients with distal DVT and was 2.1 (95% CI, 1.6-2.9) for men compared with women. At 10 years, 4.7 (95% CI, 3.8-5.8) events per 100 patient-years occurred in men with proximal DVT or PE, 2.4 (95% CI, 1.2-4.4) in men with distal DVT, 1.9 (95% CI, 1.2-2.8) in women with proximal DVT or PE and 0.9 (95% CI, 0.2-1.9) in women with distal DVT. Conclusion The ltRR of patients with first unprovoked VTE is high and dependent upon sex and VTE site.
Assuntos
Anticoagulantes/uso terapêutico , Embolia Pulmonar/tratamento farmacológico , Tromboembolia Venosa/tratamento farmacológico , Trombose Venosa/tratamento farmacológico , Adulto , Idoso , Áustria , Feminino , Fibrinolíticos/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Embolia Pulmonar/sangue , Embolia Pulmonar/complicações , Recidiva , Fatores Sexuais , Trombofilia/complicações , Fatores de Tempo , Tromboembolia Venosa/sangue , Tromboembolia Venosa/complicações , Trombose Venosa/sangue , Trombose Venosa/complicaçõesRESUMO
UNLABELLED: ESSENTIALS: In acute coronary syndromes, dual antiplatelet therapy inhibits platelets but confers a bleeding risk. Healthy male volunteers received clopidogrel or ticagrelor plus aspirin or clopidogrel or ticagrelor alone. The decrease in ß-thromboglobulin in shed blood was comparable after single and dual antiplatelet therapy. We hypothesize that patients with acute coronary syndromes may not require dual antiplatelet therapy. BACKGROUND: Dual antiplatelet therapy with a P2Y12 inhibitor and aspirin is standard in acute coronary syndromes. Dual antiplatelet therapy causes more bleeding than single antiplatelet therapy with a P2Y12 inhibitor. OBJECTIVES: To compare the effects of dual and single antiplatelet therapies on hemostatic system activation. PATIENTS/METHODS: In a randomized, parallel-group, double-blind, placebo-controlled study, 44 healthy volunteers received clopidogrel (600 mg, then 150 mg d(-1) ) and aspirin (100 mg d(-1) ) or placebo for 7 days; An additional 44 volunteers received single-dose ticagrelor (180 mg) and aspirin (300 mg) or placebo. ß-Thromboglobulin (ß-TG [IU L(-1) ]) and prothrombin fragment 1.2 (f1.2 [nmol L(-1) ]) were measured in blood obtained from bleeding time incisions. Data are given as geometric mean ratio (GMR [95% confidence interval]) to describe the differences in the first 2 h and as mean differences (Δ [95% confidence interval]) in area under the curve (AUC) to discriminate differences in effects over the total observation time. RESULTS: Clopidogrel plus aspirin and clopidogrel plus placebo reduced ß-TG by a GMR of 0.51 (0.42-0.63) and 0.54 (0.46-0.64) at 2 h. Ticagrelor plus aspirin and ticagrelor plus placebo decreased ß-TG by a GMR of 0.38 (0.26-0.57) and 0.47 (0.31-0.72). Ticagrelor plus aspirin and ticagrelor plus placebo reduced f1.2 by a GMR of 0.58 (0.45-0.75) and 0.55 (0.38-0.80); clopidogrel did not. Over 24 h, no difference in ß-TG occurred between clopidogrel plus aspirin and clopidogrel plus placebo (ΔAUC = -2.9 [-9.9 to 4.1]) or between ticagrelor plus aspirin and ticagrelor plus placebo (ΔAUC = -3.5 [-11.8 to 4.7]). No difference in f1.2 occurred between clopidogrel plus aspirin and clopidogrel plus placebo (ΔAUC = -4.2 [-10.2 to 1.8]) or between ticagrelor plus aspirin and ticagrelor plus placebo (ΔAUC = -3.6 [-10.9 to 3.7]). CONCLUSIONS: P2Y12 inhibitor monotherapy and dual antiplatelet therapy inhibit hemostatic system activation to a comparable extent.
Assuntos
Adenosina/análogos & derivados , Aspirina/administração & dosagem , Plaquetas/efeitos dos fármacos , Hemostasia/efeitos dos fármacos , Inibidores da Agregação Plaquetária/administração & dosagem , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Receptores Purinérgicos P2Y12/efeitos dos fármacos , Ticlopidina/análogos & derivados , Adenosina/administração & dosagem , Adenosina/efeitos adversos , Adolescente , Adulto , Área Sob a Curva , Aspirina/efeitos adversos , Áustria , Biomarcadores/sangue , Tempo de Sangramento , Plaquetas/metabolismo , Clopidogrel , Método Duplo-Cego , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/sangue , Inibidores da Agregação Plaquetária/efeitos adversos , Valor Preditivo dos Testes , Protrombina , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Curva ROC , Receptores Purinérgicos P2Y12/metabolismo , Ticagrelor , Ticlopidina/administração & dosagem , Ticlopidina/efeitos adversos , Fatores de Tempo , Adulto Jovem , beta-Tromboglobulina/metabolismoRESUMO
BACKGROUND: Previous analyses reported a higher risk of recurrent venous thrombosis in men than women. OBJECTIVES: We aimed to assess the risk of recurrence in men compared with women whilst taking female reproductive risk factors (oral contraception, postmenopausal hormone therapy and pregnancy) into account. In addition, we hypothesized that the sex difference in venous thrombosis was related to F9 Malmö, an X-linked prothrombotic factor. METHODS: In four pooled European cohorts (CARROT study, Glasgow, UK; CVTE study, Cambridge, UK; AUREC study, Vienna, Austria; and LETS follow-up study, Leiden, the Netherlands), the risk of recurrent venous thrombosis was calculated in men, women with reproductive risk factors and women without reproductive risk factors at the time of their first venous thrombosis. F9 Malmö was genotyped and carriers and non-carriers contrasted. RESULTS: In total, 2185 patients with a first venous thrombosis, 1043 men and 1142 women, were included. Overall, men had a 2.8-fold (95% confidence interval [CI], 2.2-3.4) higher risk of recurrent venous thrombosis than women. This risk was 5.2-fold (95% CI, 3.5-7.7) higher in men than in women with reproductive risk factors, and 2.3-fold (95% CI, 1.7-3.2) higher in men than in women without reproductive risk factors. No difference in risk of recurrence was found for carriers vs. non-carriers of F9 Malmö. CONCLUSION: Men experienced a recurrent venous thrombosis twice as often as women without reproductive risk factors. These findings indicate that men have a higher intrinsic risk of venous thrombosis than women, which is partly masked by female reproductive risk factors. The sex difference cannot be explained by F9 Malmö.
Assuntos
Fator IX/genética , Disparidades nos Níveis de Saúde , Trombose Venosa/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Coagulação Sanguínea/genética , Europa (Continente)/epidemiologia , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Fenótipo , Estudos Prospectivos , Recidiva , Medição de Risco , Fatores de Risco , Fatores Sexuais , Trombose Venosa/diagnóstico , Trombose Venosa/genética , Adulto JovemRESUMO
BACKGROUND: In order to stratify patients with a first unprovoked venous thromboembolism (VTE) according to their recurrence risk and to identify those who would actually benefit from indefinite anticoagulation, three prediction models have been developed so far; none of them has been yet externally validated. OBJECTIVE: To externally validate the Vienna Prediction Model (VPM), a prediction guide for estimating the recurrence risk after a first unprovoked VTE developed through Cox modeling and including sex, D-dimer and index VTE site as predictors. PATIENTS/METHODS: Nine hundred and four patients pooled from five prospective studies evaluating the prognostic value of D-dimer for VTE recurrence served as the validation cohort. The validity of the VPM in stratifying patients according to their relative recurrence risk (discrimination) and in predicting the absolute recurrence risk (calibration) was tested with survival analysis methods. RESULTS: The ability of the VPM to distinguish patients' risk for recurrent VTE in the validation cohort was at least as good as in the original cohort, with a calibration slope of 1.17 (95% confidence interval 0.71-1.64; P = 0.456 for the hypothesis of a significant difference from 1), and a c-statistic of 0.626 (vs. 0.651 in the original derivation cohort). The VPM absolute predictions in terms of cumulative rates tended to underestimate the observed recurrence rates at 12 months. CONCLUSIONS: By using a pooled individual patient database as a validation cohort, we confirmed the ability of the VPM to stratify patients with a first unprovoked VTE according to their risk of recurrence.
Assuntos
Tromboembolia Venosa/epidemiologia , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Fatores de RiscoRESUMO
BACKGROUND: Patients with acute coronary syndrome and concomitant atrial fibrillation may require antithrombotic triple therapy but clinical evidence of safety and efficacy is poor. We have therefore studied the combination of different antithrombotic medicines for coagulation activation in an in vivo model in the skin microvasculature. METHODS AND RESULTS: Platelet activation (ß-thromboglobulin [ß-TG]) and thrombin generation (prothrombin fragment 1 + 2 [F1+2 ], thrombin-antithrombin complex [TAT]) were studied in an open-label, randomized, parallel group trial in 60 healthy male subjects (n = 20 per group) who received ticagrelor and acetylsalicylic acid (ASA) in combination with dabigatran (150 mg bid), rivaroxaban (20 mg od) or phenprocoumon (INR 2.0-3.0). Coagulation biomarkers in shed blood were assessed at 3 h after monotherapy with the medicines under study, at 3 h after triple therapy dosing and at steady state trough conditions. Single doses of ticagrelor, dabigatran or rivaroxaban caused comparable decreases in shed blood ß-TG and were more pronounced than phenprocoumon at an INR of 2.0-3.0. In contrast, thrombin generation was more affected by rivaroxaban and phenprocoumon than by dabigatran. During triple therapy a similarly sustained inhibition of platelet activation and thrombin generation with a maximum decrease of ß-TG, F1+2 and TAT at 3 h post-dosing was noted, which remained below pre-dose levels at trough steady state. CONCLUSION: A triple therapy at steady state with ticagrelor plus ASA in combination with dabigatran or rivaroxaban is as effective as a combination with phenprocoumon for platelet activation and thrombin generation in vivo.
Assuntos
Adenosina/análogos & derivados , Anticoagulantes/administração & dosagem , Aspirina/administração & dosagem , Benzimidazóis/administração & dosagem , Coagulação Sanguínea/efeitos dos fármacos , Fibrinolíticos/administração & dosagem , Morfolinas/administração & dosagem , Femprocumona/administração & dosagem , Inibidores da Agregação Plaquetária/administração & dosagem , Tiofenos/administração & dosagem , Trombose/tratamento farmacológico , beta-Alanina/análogos & derivados , Adenosina/administração & dosagem , Adenosina/efeitos adversos , Adenosina/farmacocinética , Administração Oral , Adulto , Anticoagulantes/efeitos adversos , Antitrombina III , Aspirina/efeitos adversos , Áustria , Benzimidazóis/efeitos adversos , Benzimidazóis/farmacocinética , Biomarcadores/sangue , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Dabigatrana , Quimioterapia Combinada , Fibrinolíticos/efeitos adversos , Voluntários Saudáveis , Humanos , Coeficiente Internacional Normatizado , Masculino , Morfolinas/efeitos adversos , Morfolinas/farmacocinética , Fragmentos de Peptídeos/sangue , Peptídeo Hidrolases/sangue , Femprocumona/efeitos adversos , Ativação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/efeitos adversos , Estudos Prospectivos , Protrombina , Rivaroxabana , Tiofenos/efeitos adversos , Tiofenos/farmacocinética , Trombina/metabolismo , Trombose/sangue , Trombose/diagnóstico , Ticagrelor , Adulto Jovem , beta-Alanina/administração & dosagem , beta-Alanina/efeitos adversos , beta-Alanina/farmacocinética , beta-Tromboglobulina/metabolismoRESUMO
BACKGROUND: The optimal duration of anticoagulation for women who had venous thromboembolism (VTE) associated with estrogen use is unknown. OBJECTIVES: To test the hypothesis that women who had a first VTE while using estrogens have a low risk of recurrence. METHODS: A Prospective cohort study of 630 women (333 estrogen users, 297 non-users) with a first VTE, who were followed for an average of 69 months after anticoagulation withdrawal. Women with a previous or secondary VTE, coagulation inhibitor deficiency, lupus anticoagulant, cancer, pregnancy, requirement of long-term antithrombotic therapy or homozygosity or double heterozygosity for factor V Leiden and/or the G20210A prothrombin mutation were excluded. The endpoint was objectively documented symptomatic recurrent VTE. RESULTS: VTE recurred in 22 (7%) estrogen users and in 49 (17%) non-users. After 1, 2 and 5 years, the cumulative probability of recurrence was 1% (95% confidence interval [CI], 0-2), 1% (95% CI, 0-2) and 6% (95% CI, 3-9) among estrogen users and 5% (95% CI, 2-7), 9% (95% CI, 6-13) and 17% (95% CI, 12-22) among non-users. Compared with non-users, estrogen users had an adjusted relative risk (RR) of recurrent VTE of 0.4 (95% CI, 0.2-0.8). Compared with non-users in the respective age groups, the RR of recurrence was 0.4 (95% CI, 0.2-0.8) among estrogen-containing-contraceptive users and 0.7 (95% CI, 0.3-1.5) among women using estrogen-containing menopausal hormone therapy. CONCLUSIONS: Women who had their first VTE while using estrogens have a low risk of recurrent VTE. These women might not benefit from extended anticoagulant therapy.
Assuntos
Estrogênios/efeitos adversos , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/tratamento farmacológico , Administração Oral , Adulto , Idoso , Anticoagulantes/uso terapêutico , Áustria , Feminino , Humanos , Pessoa de Meia-Idade , Probabilidade , Estudos Prospectivos , Recidiva , Fatores de Risco , Resultado do Tratamento , Tromboembolia Venosa/etiologiaRESUMO
Venous thromboembolism (VTE) is a disease, which often recurs. The recurrence risk is highest in patients with unprovoked proximal deep-vein thrombosis (VT) or pulmonary embolism. Men have a higher risk than women. The risk is low in patients with VTE related to a temporary risk factor such as surgery or estrogen use. Other risk factors include overweight, post-thrombotic syndrome, history of VTE, residual VT or a vena cava filter. Both factor V Leiden and the prothrombin mutation confer a negligible increase in recurrence risk. High clotting factor levels, deficiency of a natural coagulation inhibitor, or hyperhomocysteinaemia are also associated with an increased risk. Reasons why routine laboratory thrombophilia screening however is no longer warranted are addressed in this article. Prediction rules combining clinical characteristics and coagulation assays have recently been developed. One such model, the Vienna Prediction Model, allows predicting recurrent VTE on the basis of VTE location, sex and D-dimer. This article describes strategies to distinguish between patients with high risk of recurrent VTE from those with a lower risk, who might not benefit from long-term antithrombotic therapy.
Assuntos
Testes de Coagulação Sanguínea/estatística & dados numéricos , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Modelos de Riscos Proporcionais , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Áustria/epidemiologia , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Prognóstico , Recidiva , Reprodutibilidade dos Testes , Medição de Risco/métodos , Sensibilidade e Especificidade , Distribuição por Sexo , Tromboembolia Venosa/sangue , Adulto JovemRESUMO
In any type of invasive surgery, the patient's individual risk of thromboembolism has to be weighed against the risk of bleeding. Based on various everyday situations in clinical routine, the purpose of the present expert recommendations is to provide appropriate perioperative and periinterventional management for patients with atrial fibrillation undergoing long-term treatment with the thrombin inhibitor dabigatran. As we currently have no routine laboratory test to measure therapeutic levels of the substance or the risk of bleeding, general measures such as a standardized documentation of the patient's history, a sufficient time interval between the last preoperative dose and the procedure, and careful control of local hemostasis should be given special attention.
Assuntos
Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/cirurgia , Benzimidazóis/efeitos adversos , Benzimidazóis/uso terapêutico , Hemorragia Pós-Operatória/induzido quimicamente , Hemorragia Pós-Operatória/prevenção & controle , Pré-Medicação/normas , beta-Alanina/análogos & derivados , Áustria , Dabigatrana , Feminino , Humanos , Masculino , Assistência Perioperatória/métodos , Assistência Perioperatória/normas , Guias de Prática Clínica como Assunto , Pré-Medicação/métodos , beta-Alanina/efeitos adversos , beta-Alanina/uso terapêuticoAssuntos
Anafilaxia/etiologia , Deficiência do Fator V/tratamento farmacológico , Fator VIIa/uso terapêutico , Hemofilia A/complicações , Hemofilia A/tratamento farmacológico , Hemorragia/prevenção & controle , Reação Transfusional , Anafilaxia/prevenção & controle , Artrodese/métodos , Cistos Ósseos/cirurgia , Hemostasia/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Plasma , Proteínas Recombinantes/uso terapêutico , Articulação Talocalcânea/cirurgia , Resultado do TratamentoRESUMO
Acquired von Willebrand (vW) syndrome is a rare bleeding disorder which is frequently associated with immunological, malignant or cardiovascular disorders. The underlying pathomechanisms, particularly in patients with IgM monoclonal gammopathies, often remain unknown. We report a patient with indolent small B-cell lymphoma (immunocytoma) and plasmacytic differentiation with an IgM kappa paraprotein who was admitted with retroperitoneal haematoma. Medical history and coagulation testing were consistent with acquired vW syndrome. vW immunohistochemistry showed normal cytoplasmic labelling of endothelial cells and megakaryocytes, whereas the lymphomatous infiltrate was negative. Acquired vW syndrome due to adsorption of vW factor on malignant cells was thus excluded. In the multimeric analysis, all multimers were present similar to that in type 1 vW syndrome, but the triplet structures were blurred. The bands on serum immunofixation electrophoresis were also atypically broadened, which suggested complex formation between the IgM and vW factor. Immunoprecipitation studies showed that the 176-kDa proteolytic fragment of vW factor co-precipitated with the IgM paraprotein in the patient but not in the controls, suggesting a specific interaction between vW factor and the paraprotein in the patient. The patient required surgery and was successfully managed by chemotherapy consisting of rituximab and fludarabin as well as plasma exchange.
Assuntos
Paraproteínas/genética , Doenças de von Willebrand/genética , Fator de von Willebrand/genética , Ensaio de Imunoadsorção Enzimática , Testes Hematológicos , Humanos , Imunoglobulina M , Masculino , Pessoa de Meia-Idade , Síndrome , Doenças de von Willebrand/diagnósticoRESUMO
Despite considerable advances in the identification of new risk factors for VTE, predicting the risk of recurrence in an individual patient remains a challenge. The impact of many of these risk factors on the recurrence risk is moderate, while the relevance of others is unknown or is regarded controversial. The determination of some markers of thrombophilia either lacks standardization or is too elaborate for routine purposes. Many patients carry more than one risk factor and their combined effect is unknown. Use of global coagulation markers that encompass the effects of clotting and/or fibrinolytic defects may improve risk assessment. In a future step, prothrombotic coagulation alterations need to be integrated with clinical risk factors. Reproducible and simple scoring systems may improve stratification of patients according to their recurrence risk and optimize duration of anticoagulant therapy.
Assuntos
Trombose Venosa/diagnóstico , Anticoagulantes/uso terapêutico , Biomarcadores/sangue , Humanos , Prognóstico , Fatores de Risco , Prevenção Secundária , Trombose Venosa/tratamento farmacológicoRESUMO
BACKGROUND: Development of factor VIII inhibitors is a serious complication in haemophilia A patients. Recombinant factor VIIa (rVIIa) is clinically effective, but its effects on haemostatic system need still to be fully elucidated. MATERIAL AND METHODS: In an open controlled study, we measured thrombin generation (peak thrombin) in venous blood and prothrombin fragment F1 + 2 (F1 + 2) and D-dimer in venous and in shed blood in five haemophilia A patients with inhibitors before and after rVIIa infusion. A total of five healthy individuals who did not receive rVIIa served as controls. RESULTS: At baseline, patients had lower mean (min-max) peak thrombin levels than controls [0.12 (0.0-0.6) vs. 186.9 (116.0-254.4) nM, P = 0.001]. After infusion, peak thrombin levels increased in average to 40.7 (28.3-51.6) nM, which translates into 80.2% (95% CI 65.4-88.6%) lower levels compared to that of controls. Mean (min-max) F1 + 2 levels in venous blood did not differ significantly between patients and controls [160.7 (89.8-331.3) vs. 160.8 (104.4-242.3) pmol L(-1)], but increased in average (min-max) by 39.4% (14.1-58.5%) after infusion. In blood emerging from incisions made to determine the bleeding (shed blood), F1 + 2 levels were lower in patients than controls [1383.3 (906.4-2044.6) vs. 2981.7 (1610.0-4539.6) pmol L(-1); P = 0.04], but were not affected by rVIIa; D-dimer levels were significantly higher in haemophiliacs than in controls and remained unchanged after infusion. CONCLUSIONS: Haemophilia A patients with factor VIII inhibitors have low thrombin generation. After rVIIa, the extent of coagulation activation as measured by levels of F1 + 2 is increased, but thrombin generation is restored to only 20%. Peak thrombin levels could reflect the effects of rVIIa on coagulation mechanisms, and their relevance with regard to the clinical coagulation defect of haemophilia A patients with factor VIII inhibitors might be evaluated.
Assuntos
Inibidores dos Fatores de Coagulação Sanguínea/sangue , Hemofilia A/sangue , Trombina/metabolismo , Adulto , Biomarcadores/sangue , Inibidores dos Fatores de Coagulação Sanguínea/efeitos adversos , Fator VIIa/administração & dosagem , Hemofilia A/complicações , Hemofilia A/tratamento farmacológico , Humanos , Infusões Intravenosas , Masculino , Tempo de Protrombina , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/sangueRESUMO
Patients with first venous thromboembolism (VTE) and high factor VIII (FVIII) are at increased risk of recurrence. It is unknown whether these patients benefit from prolonged secondary thrombophrophylaxis. In a prospective trial patients with first spontaneous VTE and FVIII levels >230 IU/dl were randomized to discontinue vitamin K Antagonist (VKA) after 6 months or to continue VKA for additional 24 months. Patients were excluded if they had a natural inhibitor deficiency, lupus anticoagulant, cancer, were pregnant, required long-term antithrombotic therapy or had acute-phase reaction. Primary study endpoints were symptomatic recurrent VTE or major bleeding within 2 years. Follow-up was continued beyond 2 years. Of 3,219 screened patients 34 met the inclusion criteria. Mean observation time was 37 months. Two of 17 patients allocated to discontinue VKA and two of 17 patients randomized to prolonged anticoagulation had recurrent VTE within 2 years. In the prolonged treatment group, one patient had recurrence during VKA therapy and one patient 4 weeks after voluntary discontinuation of VKA. One major nonfatal bleeding (severe epistaxis) after 10 months of VKA occurred in the prolonged treatment group. Five patients allocated to prolonged anticoagulation had recurrent VTE after discontinuation of VKA. The probability of recurrence at 2 years after discontinuation of VKA was 30% (95% CI 13-46%). Patients with high FVIII are at increased risk of recurrence. Our findings in a small number of patients indicate that prolonged anticoagulation seems to be effective but that the benefit is not maintained after discontinuation of anticoagulation.