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1.
Thromb Haemost ; 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34592779

RESUMO

Vaccination against the SARS-CoV-2 may lead to immunologic reactions activating the haemostatic system and resulting in both venous and arterial thromboembolism. Aquired autoimmune Haemophilia following SARS-CoV-2 vaccines were now reported 15 to 19 days (or later) after vaccination and resolution of symptoms by adequate treatment of the immunologic reaction. From patients' point of view, anticoagulants and SARS-CoV-2 vaccines share their capacity to induce thrombosis as well as bleeding and clinicians are subjected to Scylla and Charybdis when they treat patients not only with anticoagulants but also with SARS-CoV-2 vaccines. Careful analysis of coincidence and causality requires attention when reporting on acquired coagulation inhibitors regarding severity, treatments, duration and statistical risk.

2.
Semin Thromb Hemost ; 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34450680

RESUMO

Cancer patients are characterized by hypercoagulable state and an increased rate of thrombotic events, the most common being venous thromboembolism. Several hemostatic pathways that are significantly implicated in mechanisms of thromboembolic disease are also involved in growth, invasion, and metastatic spread of malignant cells as well in tumor-induced neo-angiogenesis. This close connection between cancer and the hemostatic system has prompted numerous studies on the role of alterations in the level plasma biomarkers of the different compartments of hemostasis in predicting cancer prognosis. In this review, we collect the results of several exemplificative studies that have evaluated clotting activation biomarkers in relation to different cancer outcomes with a final emphasis on current research and forthcoming directions in this field.

3.
Blood Transfus ; 2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34369869

RESUMO

Acquired platelet function disorders (PFD) are rare bleeding diseases that should be suspected in all patients with unexplained mucocutaneous bleedings of recent onset, with no previous history of haemorrhages, and with normal coagulation test and platelet count. Drug-induced platelet function bleeding disorders are the most frequent PFDs and can easily be identified on the basis of recent administration of platelet-inhibiting drugs. Apart from these, the most challenging acquired PFDs are those caused by autoimmune mechanisms. In fact, demonstration of autoantibodies inhibiting platelet function may be difficult in most non-specialised centres. Among autoimmune PFDs (aPFDs), acquired Glanzmann thrombasthenia (aGT), which is caused by autoantibodies that bind to platelet αIIbß3 integrin, inhibiting its function, is the most frequent. aGT can be associated with underlying haematological malignancies or autoimmune diseases but can also be idiopathic. More rarely, other immunemediated PFDs can occur, such as acquired delta storage pool disease (aδSPD). Treatment of aPFDs must rely on the control of acute and chronic bleedings, treatment of the underlying disease in secondary forms, and immunosuppressive treatment for autoantibody reduction or eradication. aPFDs may completely resolve upon treatment of any underlying disease that may be present. In primary aPFDs, and in the majority of secondary forms, treatment relies on immunosuppressive therapies.Here we present a systematic review of previously described immune-mediated aGT and aδSPD cases. Clinical and laboratory characteristics, treatments for the control of bleedings and for the eradication of autoantibodies, and responses to treatments are also discussed. Although no guidelines are available for the management of these very rare conditions, presentation of all cases reported so far can help clinicians in the diagnosis and treatment of these life-threatening diseases.

4.
Front Immunol ; 12: 711915, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34276706

RESUMO

Passive antibody therapy has been used to treat outbreaks of viral disease, including the ongoing pandemic of severe respiratory acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) or COVID-19. However, the real benefits of the procedure are unclear. We infused a concentrated solution of neutralizing anti-SARS-CoV-2 antibodies obtained from a convalescent donor with a single session of double filtration plasmapheresis (DFPP) into a 56-year-old woman with long history of unremitting, severe COVID-19. She was unable to establish an adequate antiviral immune response because of previous chemotherapy, including the infusion of the anti-CD20 monoclonal antibody rituximab, administered to treat a diffuse large B-cell lymphoma. The disease promptly recovered despite evidence of no endogenous anti-SARS-CoV-2 antibody production. The observation that passive antibody therapy might prove particularly effective in immunodepressed COVID-19 patients requires evaluation in prospective randomized controlled trial.


Assuntos
Anticorpos Neutralizantes/uso terapêutico , Anticorpos Antivirais/uso terapêutico , COVID-19/terapia , Imunização Passiva/métodos , Hospedeiro Imunocomprometido , Imunoglobulina G/uso terapêutico , Plasmaferese/métodos , SARS-CoV-2/genética , Antineoplásicos Imunológicos/efeitos adversos , Antivirais/uso terapêutico , COVID-19/imunologia , COVID-19/virologia , Feminino , Humanos , Imunidade/efeitos dos fármacos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Pessoa de Meia-Idade , RNA Viral/genética , Rituximab/efeitos adversos , Resultado do Tratamento
5.
Thromb Haemost ; 121(8): 992-1007, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34169495

RESUMO

BACKGROUND: One year after the declaration of the coronavirus disease 2019 (COVID-19) pandemic by the World Health Organization (WHO) and despite the implementation of mandatory physical barriers and social distancing, humanity remains challenged by a long-lasting and devastating public health crisis. MANAGEMENT: Non-pharmacological interventions (NPIs) are efficient mitigation strategies. The success of these NPIs is dependent on the approval and commitment of the population. The launch of a mass vaccination program in many countries in late December 2020 with mRNA vaccines, adenovirus-based vaccines, and inactivated virus vaccines has generated hope for the end of the pandemic. CURRENT ISSUES: The continuous appearance of new pathogenic viral strains and the ability of vaccines to prevent infection and transmission raise important concerns as we try to achieve community immunity against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) and its variants. The need of a second and even third generation of vaccines has already been acknowledged by the WHO and governments. PERSPECTIVES: There is a critical and urgent need for a balanced and integrated strategy for the management of the COVID-19 outbreaks organized on three axes: (1) Prevention of the SARS-CoV-2 infection, (2) Detection and early diagnosis of patients at risk of disease worsening, and (3) Anticipation of medical care (PDA). CONCLUSION: The "PDA strategy" integrated into state policy for the support and expansion of health systems and introduction of digital organizations (i.e., telemedicine, e-Health, artificial intelligence, and machine-learning technology) is of major importance for the preservation of citizens' health and life world-wide.


Assuntos
COVID-19/epidemiologia , COVID-19/prevenção & controle , Saúde Pública , COVID-19/diagnóstico , Teste para COVID-19/métodos , Vacinas contra COVID-19/uso terapêutico , Gerenciamento Clínico , Humanos , Programas de Imunização/métodos , Pandemias/prevenção & controle , Saúde Pública/métodos , Medição de Risco , SARS-CoV-2/isolamento & purificação
7.
Blood Transfus ; 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33819140

RESUMO

BACKGROUND: Despite significant improvements in surgical techniques and medical care, thrombotic complications still represent the primary cause of early graft failure and re-transplantation following paediatric liver transplantation. There is still no standardized approach for thrombosis prevention. MATERIALS AND METHODS: The study aimed to evaluate the effectiveness of early intravenous unfractionated heparin started 12 hours postoperatively at 10 UI/kg per hour and used a retrospective "before and after" design to compare the incidence of early thrombotic complications prior to (2002-2010) and after (2011-2016) the introduction of heparin in our institute. RESULTS: From 2002 to 2016, 479 paediatric patients received liver transplantation in our institution with an overall survival rate over one year of 0.91 (95% CI: 0.87-0.94). Of 365 eligible patients, 244 did not receive heparin while 121 did receive heparin. We reported a lower incidence of venous thrombosis (VT) in the group treated with heparin: 2.5% (3/121) vs 7.9% (19/244) (p=0.038). All clinical and laboratory variables considered potential risk factors for VT were studied. By multivariate stepwise Cox proportional hazards models, heparin prophylaxis resulted significantly associated to a reduction in VT (HR=0.29 [95% CI: 0.08-0.97], p=0.045), while age <1 year was found to be an independent risk factor for VT (HR=2.62 [95% CI: 1.11-6.21]; p=0.028). DISCUSSION: Early postoperative heparin could be considered a valid and safe strategy to prevent early VT after paediatric liver transplantation without a concomitant increase in bleeding. A future randomised control trial is mandatory in order to strengthen this conclusion.

8.
Blood Transfus ; 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33819141

RESUMO

BACKGROUND: Polycythaemia vera is a myeloproliferative neoplasm characterised by a high incidence of thrombosis. The contribution of platelets, key players in haemostasis, in this setting is still unclear. So far, the majority of studies have been focussed on specific platelet abnormalities but not on their actual capacity to form thrombi. The aim of this study was to characterise, ex vivo under flow conditions, the capacity of platelets from patients with polycythaemia vera to adhere to collagen and induce thrombus formation. MATERIALS AND METHODS: Thirty-nine patients and 30 healthy controls were studied. Thrombus formation was induced by perfusing whole blood over a collagen-coated surface, in a parallel-plate flow chamber coupled to a fluorescent microscope. This dynamic system enables platelet adhesion and thrombus formation to be followed in real time and also allows measurements of the extent of the thrombus and platelet surface antigen expression. Laboratory data were analysed in the light of the patients' main haematological parameters and therapies. RESULTS: Platelet adhesion was significantly greater in patients than in control subjects. Patient thrombi were usually larger and more complex than those formed by control platelets. A significant positive correlation was found between platelet adhesion and both the haematocrit and red blood cell count. These parameters remained significantly correlated with platelet adhesion also after multivariable analysis adjusted for gender, age, therapy and JAK2V617F allele burden. Furthermore, subjects with a haematocrit >45% had significantly greater platelet adhesion than subjects with a haematocrit <45%. DISCUSSION: Our data indicate that increased platelet adhesion participates in the thrombotic diathesis of patients with polycythaemia vera, and that the haematocrit level can affect the adhesive and thrombus forming capacities of platelets.

9.
BMC Pulm Med ; 21(1): 102, 2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33761886

RESUMO

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


Assuntos
Anticoagulantes/administração & dosagem , COVID-19/complicações , Dabigatrana/administração & dosagem , Heparina/administração & dosagem , Embolia Pulmonar/prevenção & controle , Embolia Pulmonar/virologia , Varfarina/administração & dosagem , Administração Oral , Anticoagulantes/uso terapêutico , Dabigatrana/uso terapêutico , Quimioterapia Combinada , Heparina/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Embolia Pulmonar/tratamento farmacológico , Recidiva , Varfarina/uso terapêutico
10.
Lab Chip ; 21(6): 1185, 2021 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-33687407

RESUMO

Correction for 'A microphysiological early metastatic niche on a chip reveals how heterotypic cell interactions and inhibition of integrin subunit ß3 impact breast cancer cell extravasation' by Martina Crippa et al., Lab Chip, 2021, DOI: .

12.
Lab Chip ; 21(6): 1061-1072, 2021 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-33522559

RESUMO

During metastatic progression multiple players establish competitive mechanisms, whereby cancer cells (CCs) are exposed to both pro- and anti-metastatic stimuli. The early metastatic niche (EMN) is a transient microenvironment which forms in the circulation during CC dissemination. EMN is characterized by the crosstalk among CCs, platelets, leukocytes and endothelial cells (ECs), increasing CC ability to extravasate and colonize secondary tissues. To better understand this complex crosstalk, we designed a human "EMN-on-a-chip" which involves the presence of blood cells as compared to standard metastases-on-chip models, hence providing a microenvironment more similar to the in vivo situation. We showed that CC transendothelial migration (TEM) was significantly increased in the presence of neutrophils and platelets in the EMN-on-a-chip compared to CC alone. Moreover, exploiting the EMN-on-chip in combination with multi-culture experiments, we showed that platelets increased the expression of epithelial to mesenchymal transition (EMT) markers in CCs and that the addition of a clinically approved antiplatelet drug (eptifibatide, inhibiting integrin ß3) impaired platelet aggregation and decreased CC expression of EMT markers. Inhibition of integrin ß3 in the co-culture system modulated the activation of the Src-FAK-VE-cadherin signaling axis and partially restored the architecture of inter-endothelial junctions by limiting VE-cadherinY658 phosphorylation and its nuclear localization. These observations correlate with the decreased CC TEM observed in the presence of integrin ß3 inhibitor. Our EMN-on-a-chip can be easily implemented for drug repurposing studies and to investigate new candidate molecules counteracting CC extravasation.


Assuntos
Neoplasias da Mama , Integrinas , Comunicação Celular , Linhagem Celular Tumoral , Células Endoteliais , Transição Epitelial-Mesenquimal , Feminino , Humanos , Dispositivos Lab-On-A-Chip , Microambiente Tumoral
13.
Hamostaseologie ; 41(1): 48-57, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33588455

RESUMO

Myeloproliferative neoplasms (MPNs) are clonal disorders of the hematopoietic stem cell. Classical BCR/ABL-negative MPNs include polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Thrombotic events are a major cause of morbidity and mortality in these patients. Pathogenesis of blood clotting activation involves various abnormalities of platelets, erythrocytes, and leukocytes, as well as dysfunctions of endothelial cells. Patients with MPN can be stratified in "high risk" or "low risk" of thrombosis according to established risk factors. ET and PV clinical management is highly dependent on the patient's thrombotic risk, and a risk-oriented management strategy to treat these diseases is strongly recommended. In this review, we give an overview of risk factors, pathogenesis, and thrombosis prevention and treatment in MPN.


Assuntos
Transtornos Mieloproliferativos/complicações , Trombose/prevenção & controle , Trombose/terapia , Humanos , Incidência , Fatores de Risco
14.
Blood Transfus ; 19(3): 244-252, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33539283

RESUMO

BACKGROUND: Even though it rarely influences venous thromboembolism (VTE) treatment and the fact that it is generally discouraged, thrombophilia testing is still largely prescribed. We assessed: 1) whether/how frequently Italian thrombosis centres requested thrombophilia testing; 2) what results were obtained; and 3) if the results affected treatment and clinical results. MATERIALS AND METHODS: We examined data from 4,826 VTE patients enrolled by 19 clinical centres participating in the START 2-Register. RESULTS: 57.2% of patients were tested. Numbers varied widely among centres (2.9-99.7%). Thrombophilic alterations were recorded in 18.2% of patients and the percentage of positive results was inversely correlated with that of patients tested. Significantly less patients with deep vein thrombosis (DVT) were tested, whereas more were tested when the event was idiopathic, presenting as isolated pulmonary embolism (PE), or in unusual sites. Patients with thrombophilic alterations were younger, more frequently treated with direct oral anticoagulants (DOACs), with lower mortality and less frequently discontinued anticoagulation. DOACs were more frequently prescribed in patients with heterozygous Factor V (FV) Leiden or prothrombin mutations, whereas vitamin K antagonists were preferred in patients with inhibitor deficiencies, combined alterations or antiphospholipid syndrome (APLS). There was no difference in duration of treatment among those with or without alterations, though more APLS patients received an extended treatment course. Bleeding and thrombotic complications occurred with a similar and fairly low incidence in patients with or without thrombophilic alterations. DISCUSSION: Although general testing for thrombophilia in VTE patients is currently discouraged, more than half of the VTE patients included in the START2-Register were tested. However, there were marked differences in practice between Italian thrombosis centres. About 60% of all patients with alterations were treated with DOACs, confirming that DOACs can be a useful option for treatment of thrombophilic VTE patients, with the exclusion of those with APLS.


Assuntos
Trombofilia/diagnóstico , Tromboembolia Venosa/diagnóstico , Inibidores do Fator Xa/uso terapêutico , Seguimentos , Humanos , Incidência , Itália/epidemiologia , Estudos Prospectivos , Trombofilia/tratamento farmacológico , Trombofilia/epidemiologia , Trombose/diagnóstico , Trombose/tratamento farmacológico , Trombose/epidemiologia , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/epidemiologia
15.
Artigo em Inglês | MEDLINE | ID: mdl-33523384

RESUMO

Managing anticoagulation in hematological malignancy patients with atrial fibrillation and thrombocytopenia is a clinical challenge with limited data. We aimed to identify anticoagulation management strategies and evaluate bleeding and thrombosis rates associated with each approach. A retrospective cohort study in Israel and the Netherlands was conducted. Patients with hematological malignancy and atrial fibrillation were indexed when platelets were < 50 × 109/L and followed for 30 days. The cohort included 61 patients of whom 42 (69%) had anticoagulation held at index. On multivariate analysis, holding anticoagulation was associated with age < 65 years and atrial fibrillation diagnosed within 30 days prior index. Clinically relevant bleeding was diagnosed in 7 (16.7%) and 1 (5.3%) of patients who had anticoagulation held and continued respectively, while arterial thromboembolism occurred in 1 patient in each group (2.4% and 5.3%, respectively). All-cause mortality rate was high at 45%. Accordingly, the 30-day bleeding risk may outweigh the risk of arterial thromboembolism in hematological malignancy, platelets < 50 × 109/L and atrial fibrillation.

16.
HLA ; 97(4): 375-377, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33496082

RESUMO

HLA-C*14:125 allele is identical to HLA-C*14:02:01:01 except for a single nonsynonymous mutation C199T.


Assuntos
Antígenos HLA-C , Alelos , Sequência de Bases , Antígenos HLA-C/genética , Teste de Histocompatibilidade , Humanos , Análise de Sequência de DNA
17.
J Thromb Haemost ; 19(2): 531-535, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33128325

RESUMO

BACKGROUND: Trial of Rivaroxaban in AntiPhospholipid Syndrome was a prospective randomized, open-label, noninferiority study conducted in 14 centers in Italy. Rivaroxaban was compared with warfarin for the prevention of thromboembolic events, major bleeding, and vascular death in high-risk, triple-positive patients with antiphospholipid syndrome. OBJECTIVE: The aim of this paper is to report the events during the 2-year follow-up after the study closure. METHODS: On January 28, 2018, the trial was prematurely stopped by adjudication and safety committee for an excess of events in the rivaroxaban group. Randomized patients were advised on trial results and those randomized to rivaroxaban were solicited to switch to warfarin. All 14 participating centers were asked and accepted to follow their patients for clinical events. This report describes the rate of events that occurred between January 28, 2018, and January 28, 2020. RESULTS: Of 120 randomized patients, 115 were available for follow-up. Outcome events were two in six (33.3%) patients who remained on direct oral anticoagulants (DOACs) and six in 109 (5.7%) patients on warfarin (hazard ratio [HR] 6.9; 95% confidence interval [CI] 1.4-34.5, P = .018). The two patients on DOACs (one taking dabigatran and one taking rivaroxaban) suffered from thromboembolic events, whereas of the six patients with composite outcomes on warfarin, three had thromboembolic events (HR for thrombosis 13.3; 95% CI 2.2-79.9, P = .005). CONCLUSION: These data further support the use of warfarin in high-risk patients with antiphospholipid syndrome.


Assuntos
Síndrome Antifosfolipídica , Fibrilação Atrial , Acidente Vascular Cerebral , Administração Oral , Anticoagulantes/efeitos adversos , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/tratamento farmacológico , Fibrilação Atrial/tratamento farmacológico , Dabigatrana/uso terapêutico , Humanos , Itália , Estudos Prospectivos , Rivaroxabana/efeitos adversos , Acidente Vascular Cerebral/tratamento farmacológico , Varfarina/efeitos adversos
18.
Panminerva Med ; 63(1): 51-61, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33244949

RESUMO

BACKGROUND: Findings from February 2020, indicate that the clinical spectrum of COVID-19 can be heterogeneous, probably due to the infectious dose and viral load of SARS-CoV-2 within the first weeks of the outbreak. The aim of this study was to investigate predictors of overall 28-day mortality at the peak of the Italian outbreak. METHODS: Retrospective observational study of all COVID-19 patients admitted to the main hospital of Bergamo, from February 23 to March 14, 2020. RESULTS: Five hundred and eight patients were hospitalized, predominantly male (72.4%), mean age of 66±15 years; 49.2% were older than 70 years. Most of patients presented with severe respiratory failure (median value [IQR] of PaO2/FiO2: 233 [149-281]). Mortality rate at 28 days resulted of 33.7% (N.=171). Thirty-nine percent of patients were treated with continuous positive airway pressure (CPAP), 9.5% with noninvasive ventilation (NIV) and 13.6% with endotracheal intubation. 9.5% were admitted to Semi-Intensive Respiratory Care Unit, and 18.9% to Intensive Care Unit. Risk factors independently associated with 28-day mortality were advanced age (≥78 years: odds ratio [OR], 95% confidence interval [CI]: 38.91 [10.67-141.93], P<0.001; 70-77 years: 17.30 [5.40-55.38], P<0.001; 60-69 years: 3.20 [1.00-10.20], P=0.049), PaO2/FiO2<200 at presentation (3.50 [1.70-7.20], P=0.001), need for CPAP/NIV in the first 24 hours (8.38 [3.63-19.35], P<0.001), and blood urea value at admission (1.01 [1.00-1.02], P=0.015). CONCLUSIONS: At the peak of the outbreak, with a probable high infectious dose and viral load, older age, the severity of respiratory failure and renal impairment at presentation, but not comorbidities, are predictors of 28-day mortality in COVID-19.


Assuntos
Fatores Etários , COVID-19/epidemiologia , COVID-19/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/complicações , COVID-19/mortalidade , Feminino , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença
19.
Thromb Haemost ; 121(4): 449-456, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33070301

RESUMO

BACKGROUND: Elevated levels of key enzymes of the fibrinolytic system, such as tissue plasminogen activator (tPA), are reported as predictors of poor outcome in cancer patients. Limited information is available about their potential predictive value for breast cancer (BC) risk in the general population. AIM: We examined the association of tPA levels with BC risk in a case-cohort study including women from the prospective Moli-sani cohort. METHODS: A sample of 710 women (mean age: 54.6 ± 12.1 years) was selected as a subcohort and compared with 84 BC cases, in a median follow-up of 4.2 years. Incident cases of BC were validated through medical records. tPA plasma levels were measured using an enzyme-linked immunosorbent assay kit. Hazard ratio (HR) and 95% confidence interval (CI), adjusted for relevant covariates, were estimated by a Cox regression model using the Prentice method. RESULTS: Compared with the lowest quartile (<4.9 ng/mL), women in the highest quartile of tPA (>11.2 ng/mL) had increased risk of BC (HRIVvsI: 2.20, 95% CI: 1.13-4.28) after adjusted for age, smoking, education, menopause, and residence. Further adjustment for biochemical markers did not modify this association. The risk of BC increased by 34% for each increase in 1 standard deviation of log-transformed tPA levels (p = 0.046). Elevated levels of tPA were associated mainly with estrogen-receptor-positive BC (2.08, 95% CI: 1.18-3.66). CONCLUSION: Higher levels of tPA, reported to predict cardiovascular risk, are a potential biomarker for BC risk, supporting the hypothesis of a "common soil" linking the pathogenic mechanisms of hormone-dependent tumors and cardiovascular disease.

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