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1.
Liver Int ; 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32052552

RESUMO

BACKGROUND AND AIMS: Non-O blood-type (BT) is a risk factor for thromboses, which has been attributed to its effects on von Willebrand factor (VWF)/factor VIII (FVIII) levels. Although high VWF/FVIII may be risk factors for portal vein thrombosis (PVT) in patients with advanced chronic liver disease (ACLD), the impact of BT on PVT is unknown. We aimed to assess (I) whether non-O-BT is a risk factor for PVT and (II) whether non-O-BT impacts VWF/factor VIII in patients with ACLD. METHODS: Retrospective analysis comprising two cohorts: (I) 'U.S.' including all adult liver transplantations in the U.S. in the MELD era and (II) 'Vienna' comprising patients with a hepatic venous pressure gradient (HVPG)≥6mmHg. RESULTS: (I) The 'U.S.-cohort' included 84,947 patients (non-O:55.43%). The prevalence of PVT at the time of listing (4.37%vs.4.56%;P=0.1762) and at liver transplantation (9.56%vs.9.33%;P=0.2546) was similar in patients with O- and non-O-BT. (II) 411 patients were included in the 'Vienna-cohort' (non-O:64%). Mean HVPG was 18(9)mmHg and 90% had an HVPG≥10mmHg. Patients with non-O-BT had slightly increased VWF levels (318(164)%vs.309(176)%;P=0.048;increase of 23.8-23.9% in adjusted analyses), but this difference was driven by patients with less advanced disease. However, non-O-BT explained only 1% of the variation in VWF and had no effect on FVIII. CONCLUSIONS: Although non-O-BT impacts VWF in patients with early-stage ACLD, its contribution to VWF variation is considerably smaller than in the general population. Moreover, non-O-BT had no impact on FVIII. These findings may explain the absence of an association between non-O-BT and PVT in patients with advanced cirrhosis.

2.
ESMO Open ; 5(1)2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31958288

RESUMO

Patients with cancer are at an increased risk of symptomatic venous thromboembolism (VTE). In addition, an increasing number of patients with incidental thromboembolic events have been recorded in clinical practice. Therapeutic anticoagulation is crucial to prevent thrombus progression and reduce risk of recurrence; however, this comes at the price of an increased bleeding risk, which necessitates a personalised approach to choose the most appropriate type of therapy. Over the last decade, low-molecular-weight heparin has been the preferred anticoagulant agent for patients with cancer-associated thrombosis due to better efficacy and similar safety profile compared with vitamin K antagonists. While direct oral anticoagulants (DOAC) have emerged as new option for treatment of VTE in a general population, only limited data have been available specifically for patients with cancer until recently. Randomised, controlled trials have now been published, establishing DOAC as an alternative for the treatment of cancer-associated thrombosis. However, the improvement in the therapeutic armamentarium is accompanied by a number of special considerations. For instance, risk of bleeding is elevated in patients with cancer-associated VTE receiving DOAC, especially in certain tumour types (eg, gastrointestinal), and no guidance exists regarding their use in patients with severe thrombocytopaenia. Furthermore, DOAC are prone to certain drug-drug interactions and their effect might be altered due to nausea and vomiting in patients receiving chemotherapy. Here, we provide guidance on how to treat cancer-associated VTE and how new evidence from randomised controlled trials can be implemented in clinical practice. There are still clinical scenarios where robust evidence is lacking and treatment recommendations are based on extrapolations from other populations or expert opinion only. Therefore, additional research in special subpopulations is needed to optimise management of patients in challenging clinical scenarios.

3.
Hamostaseologie ; 40(1): 38-46, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31986545

RESUMO

In this concise review, we discuss some common clinical challenges in the management of patients with cancer-associated venous thromboembolism (VTE), a frequent complication in patients with cancer that increases morbidity and mortality. While direct oral anticoagulants (DOACs) have been established in clinical practice for anticoagulation in patients with VTE without cancer, their efficacy and safety in patients with cancer have not been assessed in randomized controlled trials until recently. The choice of the appropriate anticoagulant agent in the era of DOACs to treat patients with cancer-associated VTE is based on balancing the risk of recurrence against the risk of bleeding, and potential drug-drug interactions. However, the management of patients is challenged by special scenarios such as incidentally diagnosed pulmonary embolism and catheter-related thrombosis, and sometimes complicated by concomitant thrombocytopenia. We provide guidance for management of cancer-associated VTE in different clinical scenarios in a case-based manner and briefly review recent clinical studies and guidelines to explain our approach to management of the cases.

4.
Exp Mol Med ; 52(1): 66-78, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31956273

RESUMO

Patients with antiphospholipid syndrome (APS) are at high risk of developing venous and arterial thromboembolism (TE). The role of platelets in the pathogenesis of these prothrombotic conditions is not yet fully understood. The aim of this study was to gain mechanistic insights into the role of platelets in APS by comparing the platelet proteome between lupus anticoagulant (LA)-positive patients with (LA+ TE+) and without a history of TE (LA+ TE-) and healthy controls. The platelet proteome of 47 patients with LA, 31 with a history of TE and 16 without thrombotic history, and 47 healthy controls was analyzed by two-dimensional differential in-gel electrophoresis and mass spectrometry to identify disease-related proteins. Afterward, selected LA-related platelet proteins were validated by western blot and ELISA. Alterations of 25 proteins were observed between the study groups. STRING pathway analysis showed that LA-related protein profiles were involved in platelet activation, aggregation, and degranulation. For example, protein disulfide isomerase family members, enzymes that promote thrombosis, were upregulated in platelets and plasma of LA+ TE+ patients. Leukocyte elastase inhibitor (SERPINB1), an antagonist of neutrophil extracellular trap (NET) formation, was decreased in platelets of LA+ TE+ patients compared to healthy controls. Additionally, citrullinated histone H3, a NET-specific marker, was increased in plasma of LA+ TE+ patients. These findings suggest that decreased platelet SERPINB1 levels favor prothrombotic NETosis, especially in LA+ TE+ patients. Our findings reveal protein abundance changes connected to altered platelet function in LA-positive patients, thus suggesting a pathogenic role of platelets in thrombotic complications in APS.

5.
Thromb Res ; 187: 9-17, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31945589

RESUMO

BACKGROUND: Haemostatic activation and hypercoagulability are frequently observed in patients with metastatic colorectal cancer (mCRC), increase risk of venous thromboembolism (VTE) and have been implicated in tumour proliferation and progression. To date, the association of haemostatic biomarkers with oncologic outcomes including overall survival (OS), progression free survival (PFS) and disease control rate (DCR) is incompletely understood. METHODS: Within the framework of the Vienna Cancer and Thrombosis Study, a prospective observational cohort study, we conducted an exploratory analysis to investigate the association of six known biomarkers of haemostasis with oncologic outcomes in 99 patients with mCRC prior to chemotherapy initiation. RESULTS: Patients with high levels of factor VIII activity (FVIII), D-dimer, prothrombin fragment 1 + 2 (F1 + 2) and fibrinogen (defined as levels >75th percentile) had significantly shorter median OS than patients with lower levels. Elevation of four biomarkers was associated with mortality in multivariable analysis, adjusting for age, sex, number of metastatic sites and VTE (hazard ratio [95% CI] for death per doubling of levels: FVIII: 2.06 [1.28-3.30]; sP-selectin: 1.55 [1.07-2.24]; D-dimer: 1.40 [1.18-1.65]; F1 + 2: 1.64 [1.10-2.46]). Patients with elevated levels had numerically shorter median PFS across all markers and disease control rate (DCR) was significantly smaller in those with high levels of FVIII and F1 + 2 (adjusted odds ratio [95% CI] for DCR per doubling of levels: 0.23 [0.09-0.62] and 0.36 [0.16-0.82]) compared to patients with lower levels. CONCLUSION: Specific elevated haemostatic biomarkers are associated with higher mortality and partially with worse response to chemotherapy in patients with mCRC.

6.
Haematologica ; 105(1): 218-225, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31048354

RESUMO

Pancreatic cancer is associated with a high incidence of venous thromboembolism. Neutrophils have been shown to contribute to thrombosis in part by releasing neutrophil extracellular traps (NET). A recent study showed that increased plasma levels of the NET biomarker, citrullinated histone H3 (H3Cit), are associated with venous thromboembolism in patients with pancreatic and lung cancer but not in those with other types of cancer, including breast cancer. In this study, we examined the contribution of neutrophils and NET to venous thrombosis in nude mice bearing human pancreatic tumors. We found that tumor-bearing mice had increased circulating neutrophil counts and levels of granulocyte-colony stimulating factor, neutrophil elastase, H3Cit and cell-free DNA compared with controls. In addition, thrombi from tumor-bearing mice contained increased levels of the neutrophil marker Ly6G, as well as higher levels of H3Cit and cell-free DNA. Thrombi from tumor-bearing mice also had denser fibrin with thinner fibers consistent with increased thrombin generation. Importantly, either neutrophil depletion or administration of DNase I reduced the thrombus size in tumor-bearing but not in control mice. Our results, together with clinical data, suggest that neutrophils and NET contribute to venous thrombosis in patients with pancreatic cancer.

7.
Transl Res ; 215: 41-56, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31525325

RESUMO

A prothrombotic state is frequently observed in patients with cancer and contributes to the risks of venous thromboembolism (VTE), arterial thromboembolism (ATE), tumor progression, and death. Altered ex vivo properties of plasma clot formation and lysis have been observed in patients with cancer. The aim of this prospective study was to comprehensively characterize the relationship between plasma clot properties, inflammation, hypercoagulability, thrombotic complications, and mortality in patients with cancer using a tissue-factor-based turbidimetric assay of clot formation and lysis. Turbidity parameters were determined in 815 patients with newly-diagnosed or recurrent cancer and 97 healthy controls. Patients were followed-up for 2 years and rates of VTE (n = 72 events), ATE (n = 21 events), and death (n = 304 events) were assessed. Compared to controls, cancer patients' turbidity profiles showed an increased clot formation potential and higher resistance toward fibrinolysis. Elevated biomarkers of inflammation and hemostasis, such as C-reactive protein, FVIII, and thrombin generation explained substantial amounts of variation in turbidity parameters. In a prospective analysis, altered parameters of clot formation identified cancer patients at high risk of ATE (Hazard ratio [HR] per doubling of peak absorbance: 4.43, 95% CI: 1.50-13.07, P = 0.007) and death (HR per doubling of peak absorbance: 2.73, 2.00-3.72, P< 0.0001); these findings were independent of other prognostic covariates. Contrarily, turbidity parameters were not associated with risk of VTE (HR per doubling of peak absorbance: 1.15, 0.66-2.01, P = 0.62). We conclude that patients with cancer have altered ex vivo properties of clot formation which predict risks of ATE and mortality but not VTE.

8.
Eur Respir J ; 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31727694

RESUMO

INTRODUCTION: In cancer patients, current guidance suggests similar treatment for incidental and symptomatic venous thromboembolism (VTE), mainly based on retrospective data. We aimed to evaluate anticoagulant therapy in cancer patients with incidental and symptomatic VTE. METHODS: The Hokusai VTE Cancer study was a randomised controlled trial comparing edoxaban with dalteparin for cancer-associated VTE. The primary outcome was the composite of first recurrent VTE or major bleeding. Secondary outcomes included major bleeding, recurrent VTE, and mortality. Outcomes in patients with incidental and symptomatic VTE were evaluated during the 12-month study period. RESULTS: A total of 331 patients with incidental VTE and 679 with symptomatic VTE were enrolled, of whom the index event was confirmed by an independent radiologist. Median durations of anticoagulant treatment were 195 days and 189 days, respectively. In patients with incidental VTE, the primary outcome occurred in 12.7%, major bleeding in 6.6%, and recurrent VTE in 7.9% of patients. Out of the 26 VTE recurrences in patients with incidental VTE, 5 (31%) were incidental, 7 (44%) were symptomatic and 4 (25%) were deaths for which PE could not be ruled out. In patients with symptomatic VTE, the primary outcome occurred in 13.8%, major bleeding in 4.9%, and recurrent VTE in 10.9% of patients. All-cause mortality was similar in both groups. CONCLUSION: Clinical adverse outcomes are substantial in both cancer patients with incidental and symptomatic VTE, supporting current guideline recommendations that suggest treating incidental VTE in the same manner as symptomatic VTE.

9.
J Clin Med ; 8(10)2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31581493

RESUMO

The exact contribution of neutrophils to post-resuscitative brain damage is unknown. We aimed to investigate whether neutrophil extracellular trap (NET) formation in the early phase after return of spontaneous circulation (ROSC) may be associated with poor 30 day neurologic function in cardiac arrest survivors. This study prospectively included adult (≥18 years) out-of-hospital cardiac arrest (OHCA) survivors with cardiac origin, who were subjected to targeted temperature management. Plasma levels of specific (citrullinated histone H3, H3Cit) and putative (cell-free DNA (cfDNA) and nucleosomes) biomarkers of NET formation were assessed at 0 and 12 h after admission. The primary outcome was neurologic function on day 30 after admission, which was assessed using the five-point cerebral performance category (CPC) score, classifying patients into good (CPC 1-2) or poor (CPC 3-5) neurologic function. The main variable of interest was the effect of H3Cit level quintiles at 12 h on 30 day neurologic function, assessed by logistic regression. The first quintile was used as a baseline reference. Results are given as crude odds ratio (OR) with 95% confidence interval (95% CI). Sixty-two patients (79% male, median age: 57 years) were enrolled. The odds of poor neurologic function increased linearly, with 0 h levels of cfNDA (crude OR 1.8, 95% CI: 1.2-2.7, p = 0.007) and nucleosomes (crude OR 1.7, 95% CI: 1.0-2.2, p = 0.049), as well as with 12 h levels of cfDNA (crude OR 1.6, 95% CI: 1.1-2.4, p = 0.024), nucleosomes (crude OR 1.7, 95% CI: 1.1-2.5, p = 0.020), and H3Cit (crude OR 1.6, 95% CI: 1.1-2.3, p = 0.029). Patients in the fourth (7.9, 95% CI: 1.1-56, p = 0.039) and fifth (9.0, 95% CI: 1.3-63, p = 0.027) H3Cit quintile had significantly higher odds of poor 30 day neurologic function compared to patients in the first quintile. Increased plasma levels of H3Cit, 12 h after admission, are associated with poor 30 day neurologic function in adult OHCA survivors, which may suggest a contribution of NET formation to post-resuscitative brain damage and therefore provide a therapeutic target in the future.

10.
Res Pract Thromb Haemost ; 3(4): 578-588, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31624777

RESUMO

Atrial fibrillation (AF) is a frequent comorbid condition in patients with end-stage renal disease on hemodialysis (HD) with a prevalence of up to 27%. The incidence rate of stroke in AF patients on HD is approximately 5%. The AF-associated risk of stroke is a major clinical challenge because current evidence for anticoagulation in HD patients with AF is based on observational data. Results from these observational studies is largely contradictory because they do not show a clear benefit of vitamin K antagonists over no treatment in terms of stroke prevention, and they show an increased risk of hemorrhage associated with anticoagulation treatment in HD patients. HD patients were not included in randomized trials of the direct oral anticoagulants (DOACs), and therefore there is no evidence to support efficacy and safety of DOACs compared to vitamin K antagonists in HD patients. The pharmacological characteristics of DOACs are of particular interest in the HD setting. The factor Xa inhibitors rivaroxaban, apixaban, and edoxaban are not predominantly eliminated via the kidneys. The thrombin inhibitor dabigatran is 80% eliminated via the kidneys but is dialyzable due to its low protein binding. In this narrative review, we examine the current state of evidence regarding the prevalence of AF in patients on HD, the associated risk of stroke, and the efficacy and safety of anticoagulation for stroke prevention in the HD setting. Further, based on the pharmacokinetic properties of DOACs, we discuss their potential use in patients on HD and ongoing randomized trials.

11.
Wien Klin Wochenschr ; 131(21-22): 558-566, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31535221

RESUMO

BACKGROUND: Hemophilia is a congenital bleeding disorder with an estimated frequency of 1:10,000 births. Repeated joint bleeding is a hallmark of the disorder and leads to painful hemophilic arthropathy. Regular exercise can help improve joint stability and function, reduce the risk of injury and bleeding and improve physical fitness and quality of life. This method paper describes an online training concept aiming to offer access to appropriate exercise instructions for people with hemophilia who are not able to attend regular training at a hemophilia center. METHODS: The online exercise program is accessible through the homepage of the Department of Physical Medicine, Rehabilitation and Occupational Medicine of the Medical University Vienna as well as through scanning a QR code printed on information material using a smart phone or tablet. RESULTS: The program contains exercises to improve mobility, coordination, muscular strength and flexibility. A brief introduction is given by a hematologist, a pediatrician and a physiatrist. An introductory video informs about contraindications and essential precautions, such as medical attendance and sufficient factor therapy to consider before starting the training. Another video gives advice on the exercise composition. The demonstrated exercises are explained by a physician and are available for adults and children. To individualize training recommendations and offer further diagnostic tools and physical treatment options as necessary, the Department of Physical Medicine, Rehabilitation and Occupational Medicine of the Medical University of Vienna will establish consultation hours for people with hemophilia. CONCLUSION: As hemophilia is an orphan disease, patients are mainly treated in specialized centers. For patients who live far from these centers or have limited access to a training there for other reasons, the physical medicine consultation hour and the implementation of online exercise instructions offer individually adapted exercise information for a regular home-based training to benefit from increased physical fitness and joint stability.


Assuntos
Artralgia/terapia , Hemofilia A , Aptidão Física , Adulto , Artralgia/etiologia , Criança , Exercício/fisiologia , Terapia por Exercício , Hemofilia A/complicações , Humanos , Qualidade de Vida
12.
Lancet Oncol ; 20(10): e566-e581, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31492632

RESUMO

Venous thromboembolism (VTE) is the second leading cause of death in patients with cancer. These patients are at a high risk of VTE recurrence and bleeding during anticoagulant therapy. The International Initiative on Thrombosis and Cancer is an independent academic working group aimed at establishing a global consensus for the treatment and prophylaxis of VTE in patients with cancer. The International Initiative on Thrombosis and Cancer last updated its evidence-based clinical practice guidelines in 2016 with a free, web-based mobile phone application, which was subsequently endorsed by the International Society on Thrombosis and Haemostasis. The 2019 International Initiative on Thrombosis and Cancer clinical practice guidelines, which are based on a systematic review of the literature published up to December, 2018, are presented along with a Grading of Recommendations Assessment Development and Evaluation scale methods, with the support of the French National Cancer Institute. These guidelines were reviewed by an expanded international advisory committee and endorsed by the International Society on Thrombosis and Haemostasis. Results from head-to-head clinical trials that compared direct oral anticoagulant with low-molecular-weight heparin are also summarised, along with new evidence for the treatment and prophylaxis of VTE in patients with cancer.

13.
Res Pract Thromb Haemost ; 3(3): 503-514, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31294335

RESUMO

Background: Cancer-associated venous thromboembolism (VTE) is an important complication in the course of a malignant disease. Low ADAMTS-13 (a disintegrin-like and metalloproteinase with thrombospondin type 1 motif 13) and increased von Willebrand Factor (VWF) levels in cancer patients have been described numerously. Objectives: Investigation of the influence of ADAMTS-13 and VWF on the probability of VTE and survival in malignancy. Patients/Methods: In the framework of the ongoing prospective Cancer and Thrombosis Study (CATS) ADAMTS-13 activity and VWF antigen levels were investigated in cancer patients. Results: In total, 795 patients with various tumor types (364 female/431 male, median age 62 years) were included; of those, 56 developed VTE and 359 patients died during a median follow-up time of 730 days. The hazard ratio (HR) of VTE per doubling of VWF level was 1.56 (95% confidence interval [CI] 1.13-2.16) in multivariable competing risk analysis. ADAMTS-13 levels showed no correlation with the incidence of VTE in univariate competing risk analysis. The HR of mortality per doubling of VWF level was 1.46 (95% CI 1.28-1.66) and per SD increment of ADAMTS-13was 0.90 (95% CI 0.81-1.00) in multivariable Cox regression analysis. Patients with VWF >75th percentile and concomitant low (<25th percentile) or medium (25-75th percentile) ADAMTS-13 values had the highest probability of mortality (HR 4.31 and 4.75, respectively). Conclusions: High VWF levels were significantly associated with the risk of developing VTE in cancer patients, whereas ADAMTS-13 was not. Low ADAMTS-13 and increased VWF levels were independently associated with worse overall survival.

15.
J Thromb Haemost ; 17(9): 1478-1488, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31177606

RESUMO

BACKGROUND: In a large proportion of patients with a mild to moderate bleeding tendency no diagnosis can be established (bleeding of unknown cause, BUC). OBJECTIVES: To investigate possible dysfunctions in thrombin generation and plasma clot formation and lysis in patients with BUC from the Vienna Bleeding Biobank (VIBB). PATIENTS AND METHODS: Thrombin generation and plasma clot properties of 382 BUC patients were compared to those of 100 healthy controls and 16 patients with factor VIII (FVIII) activity ≤50%. RESULTS: Thrombin generation was significantly impaired in BUC patients compared to healthy controls, exhibiting a prolonged lag time and time to peak and decreased maximum thrombin generation, velocity index, and area under the curve (AUC). The assessment of clot formation and lysis in BUC patients revealed a lower clot formation rate (Vmax), resulting in a longer TTP, increased absorbance (ΔAbs), and a shorter clot lysis time (CLT) than in healthy controls. Comparing patients with FVIII activity ≤ 50% to those with BUC, parameters of thrombin generation and clot formation and lysis were either stronger or comparably impaired. Bleeding severity did not correlate with parameters of thrombin generation, clot formation, or clot lysis. CONCLUSION: Patients with BUC have an impaired hemostatic capacity reflected by a lower thrombin-generation potential, a lower clot formation rate, increased clot turbidity, and shorter clot lysis time, which might contribute to their increased bleeding tendency. Assays monitoring these parameters can alert physicians of hemostatic impairment and should be considered in situations where traditional hemostatic lab tests fail to reveal the clinical bleeding tendency.

17.
Semin Thromb Hemost ; 45(4): 334-341, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31041803

RESUMO

Venous thromboembolism (VTE) is a common complication in patients with primary brain tumors, with up to 20% of patients per year having a VTE event. Clinical risk factors for VTE include glioblastoma subtype, paresis, or surgery. Furthermore, specific factors playing a role in tumor biology were recently identified to predispose to prothrombotic risk. For instance, mutations in the isocitrate dehydrogenase 1 (IDH1) gene, which occurs in a subgroup of glioma, correlate with risk of VTE, with low incidence in patients with presence of an IDH1 mutation compared with those with IDH1 wild-type status. In addition, expression of the glycoprotein podoplanin on brain tumors was associated with both intratumoral thrombi and high risk of VTE. As podoplanin has the ability to activate platelets, a mechanistic role of podoplanin-mediated platelet activation in VTE development has been suggested. From a clinical point of view, the management of patients with primary brain tumors and VTE is challenging. Anticoagulation is required to treat patients; however, it is associated with increased risk of intracranial hemorrhage. This review focuses on describing the epidemiology, risk factors, and mechanisms of brain tumor-associated thrombosis and discusses clinical challenges in the prevention and treatment of VTE in patients with brain tumors.


Assuntos
Anticoagulantes/uso terapêutico , Neoplasias Encefálicas/complicações , Glioblastoma/complicações , Trombose/tratamento farmacológico , Tromboembolia Venosa/tratamento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Glioblastoma/genética , Glioblastoma/metabolismo , Humanos , Isocitrato Desidrogenase/genética , Isocitrato Desidrogenase/metabolismo , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Mutação , Ativação Plaquetária , Trombose/diagnóstico , Trombose/etiologia , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/etiologia
18.
J Thromb Haemost ; 17(8): 1335-1344, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31099477

RESUMO

BACKGROUND: Patients with cancer are at risk of developing arterial thromboembolism (ATE). With the prevalence of cancer and cardiovascular diseases on the rise, the identification of risk factors for ATE in patients with cancer is of emerging importance. OBJECTIVES: As data on the association of potential biomarkers with risk of ATE in patients with cancer are scarce, we conducted a cohort study with the aim to identify blood-based biomarkers for ATE risk prediction in patients with cancer. PATIENTS/METHODS: Overall, 1883 patients with newly diagnosed cancer or progressive disease after complete or partial remission were included and followed for 2 years. Venous blood was drawn at study inclusion for measurement of complete blood count parameters, total cholesterol, d-dimer, and soluble P-selectin (sP-selectin) levels. RESULTS: The 2-year cumulative incidence of ATE was 2.5%. In univariable analysis, red cell distribution width (subdistribution hazard ratio (SHR) per doubling: 4.4, 95% CI: 1.4-14.1), leukocyte count (1.2, 1.1-1.5), neutrophil count (1.6, 1.1-2.3), and sP-selectin levels (1.9, 1.3-2.7) were associated with risk of ATE in patients with cancer; d-dimer was not associated with the risk of ATE (1.1, 0.9-1.4). After adjustment for age, sex, and smoking status the association prevailed for the neutrophil count (adjusted [adj.] SHR per doubling: 1.6, 1.1-2.4), and sP-selectin levels (1.8, 1.2-2.8). CONCLUSIONS: An elevated absolute neutrophil count and higher sP-selectin levels were associated with an increased risk of ATE in patients with cancer. Their role for predicting cancer-related ATE needs to be validated in further studies.

19.
Res Pract Thromb Haemost ; 3(2): 207-216, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31011705

RESUMO

Background: Exposure to vitamin K antagonists (VKA) has been suggested to accelerate progression of chronic kidney disease (CKD) but robust clinical data are currently lacking. Methods: We retrospectively evaluated the impact of VKA exposure on kidney function in patients with atrial fibrillation (AF) and CKD stage 3/4. Patients were prospectively followed within a primary care electronic database (median follow-up of 1.45 years). The kidney function trajectory over time, defined as the annualized change in estimated glomerular filtration rate (eGFR), was analyzed with linear mixed-effects regression including propensity score adjustment. Results: 14 432 patients (median age 78 years, median CHA 2 DS 2-VASc score 4 points) contributed 97 792 eGFR measurements (mean 6.8 measurements/patient; range: 1-197). Mean baseline eGFR was 50.3 mL/min/1.73 m2; and declined by 1.10 mL/min/1.73 m2/year (95% CI: 0.91-1.28, P < 0.0001). In 7409 patients with VKA exposure, CKD progression was significantly faster compared to patients without VKA exposure (5-year absolute eGFR loss from baseline: 6.0 mL/min/1.73 m2 vs 4.5 mL/min/1.73 m2, for an absolute 5-year excess eGFR decline with VKA exposure of 1.5 mL/min/1.73 m2 (95% CI: 0.4-2.7, P = 0.002). These results prevailed upon adjusting for CHA 2 DS 2-VASc score and other potential imbalances in prognostic variables, and in several sensitivity analyses. In the group without documented VKA exposure, 1775 VKA patients (24%) and 1012 patients (14%) developed a 30% decline in eGFR during follow-up (P < 0.0001). Conclusions: In patients with AF and CKD, VKA use is associated with accelerated eGFR decline. Within the limitations of a retrospective analysis, this finding supports the "VKA-renal-calcification hypothesis." However, although statistically significant, the excess loss in eGFR over 5 years with VKA was modest.

20.
Br J Haematol ; 186(2): 311-320, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30968400

RESUMO

Prior studies indicate that neutrophil extracellular traps (NETs) are associated with arterial thromboembolism (ATE) and mortality. We investigated the association between NET formation biomarkers (citrullinated histone H3 [H3Cit], cell-free DNA [cfDNA], and nucleosomes) and the risk of ATE and all-cause mortality in patients with cancer. In this prospective cohort study, H3Cit, cfDNA and nucleosome levels were determined at study inclusion, and patients with newly diagnosed cancer or progressive disease after remission were followed for 2 years for ATE and death. Nine-hundred and fifty-seven patients were included. The subdistribution hazard ratios for ATE of H3Cit, cfDNA and nucleosomes were 1·0 per 100 ng/ml increase (95% confidence interval [95% CI]: 0·7-1·4, P = 0·949), 1·0 per 100 ng/ml (0·9-1·2, P = 0·494) increase and 1·1 per 1-unit increase (1·0-1·2, P = 0·233), respectively. Three-hundred and seventy-eight (39·5%) patients died. The hazard ratio (HR) for mortality of H3Cit and cfDNA per 100 ng/ml increase was 1·1 (1·0-1·1, P < 0·001) and 1·1 (1·0-1·1, P < 0·001), respectively. The HR for mortality of nucleosome levels per 1-unit increase was 1·0 (1·0-1·1, P = 0·233). H3Cit, cfDNA and nucleosome levels were not associated with the risk of ATE in patients with cancer. Elevated H3Cit and cfDNA levels were associated with higher mortality in patients with cancer.

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