CX3CR1/CX3CL1 Axis Mediates Platelet-Leukocyte Adhesion to Arterial Endothelium in Younger Patients with a History of Idiopathic Deep Vein Thrombosis.

Mechanisms linking deep vein thrombosis (DVT) and subclinical atherosclerosis and risk of cardiovascular events are poorly understood. The aim of this study was to investigate the potential impact of CX3CR1/CX3CL1 axis in DVT-associated endothelial dysfunction. The study included 22 patients (age: 37.5 ± 8.2 years) with a history of idiopathic DVT and without known cardiovascular risk factors and 23 aged-matched control subjects (age: 34 ± 7.8 years). Flow cytometry was used to evaluate peripheral markers of platelet activation, leukocyte immunophenotypes and CX3CR1/CX3CL1 expression in both groups. A flow chamber assay was employed to measure leukocyte arrest under dynamic conditions. Platelet activation and the percentage of circulating CX3CR1-expressing platelets, CX3CR1-expressing platelet-bound monocytes and CD8+ lymphocytes were higher in patients with DVT than in controls. Additionally, patients with DVT had increased plasma levels of CX3CL1, soluble P-selectin and platelet factor 4/CXCL4. Interestingly, this correlated with enhanced platelet-leukocyte interaction and leukocyte adhesion to TNFα-stimulated arterial endothelial cells, which was partly dependent on endothelial CX3CL1 upregulation and increased CX3CR1 expression on platelets, monocytes and lymphocytes. In conclusion, increased CX3CR1 expression on circulating platelets may constitute a prognostic marker for long-term adverse cardiovascular events in patients with DVT. Blockade of CX3CL1/CX3CR1 axis may represent a new therapeutic strategy for the prevention of cardiovascular comorbidities associated with DVT.

Should we look for silent pulmonary embolism in patients with deep venous thrombosis?

BACKGROUND: Asymptomatic or silent pulmonary embolism (S-PE) in patients with deep vein thrombosis has been the focus of numerous publications with the objective of determining the incidence of S-PE and assessing whether its existence has any clinical or therapeutic consequences that outweigh the risks associated with the diagnostic tests performed and the increased healthcare costs. The objectives were to assess the incidence of S-PE using computed tomography angiogram (CTA), to understand the epidemiological factors that might trigger embolism, and to assess whether D-dimer (DD) predicts the existence of S-PE's. METHODS: A prospective and consecutive assessment of 103 hospitalized patients with lower limb DVT in the absence of PE symptoms, using CT scan. DD was quantified before anticoagulation. The risk factors and characteristics of the DVT were studied. A three-year follow-up assessing risk recurrence and clinical outcome was performed. RESULTS: The incidence of S-PE was 66%. In 77% of these cases, the main and lobar pulmonary arteries were affected. Iliac and femoral DVTs most often produced S-PE. ROC curve with a DD value higher than 578 ng/ml provided good sensitivity but low specificity to identify patients with S-PE. Diagnosis entailed higher hospitalization expenses. No significant recurrence rate of thrombotic events was observed in the S-PE group during the follow-up. CONCLUSIONS: The incidence of S-PE in lower-limb DVT is high, but in the absence of symptoms, diagnosis does not appear to be necessary, as there are no short- or long-term clinical or therapeutic consequences.

[Factors related to the risk of thrombosis in patients with lupus and antiphospholipid antibodies]. / Factores relacionados con el riesgo de trombosis en pacientes con lupus y positividad para anticuerpos antifosfolipídicos.

BACKGROUND AND OBJECTIVE: Antiphospholipid antibodies (aPL) are frequently associated with eritematosus systemic lupus (SLE) and increases the risk of thrombosis. The aim of the study was to analize risk factors of thrombosis and its temporal profile in subjects with SLE. PATIENTS AND METHOD: One hundred and two SLE patients -mean age: 37.5 years (range: 8-85); 90 women; mean of follow-up: 72 months (range: 9-324); 41 (40.2%) with aPL positive- were included in the study. Actuarial Kaplan-Meier curves were used to assess the thrombosis risk and Cox proportional hazard model was used to evaluate factors associated with the risk. RESULTS: 13 thrombotic events occurred in the group with aPL positive (mean of follow up: 83.5 months) and 5 events in aPL negative group (mean of follow up: 72 months). The event-rates were 3.93 and 0.96/100 patients/year for each group, respectively. Survival curves showed a significantly higher risk of thrombotic events in the patients with positive aPL as compared to the aPL negative group, and the risk still present throughout the observational time. Activated partial thromboplastine time up to 37 s was significantly associated with thrombosis risk (p = 0.003). Furthermore, positivity of lupus anticoagulant and proteinuria > 2.5 g/day tended to increase thrombotic risk, although they did not achieve statistical significance. CONCLUSIONS: In patients with SLE and aPL, risk of first thrombosis remains over the years, and a large activated partial thromboplastine time was the most important risk factor.

Hipogammaglobulinemia secundaria a enteritis actínica / Hypogammaglobulinemia secundary to actinic enteritis

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Factores relacionados con el riesgo de trombosis en pacientes con lupus y positividad para anticuerpos antifosfolipídicos / Factors related to the risk of thrombosis in patients with lupus and antiphospholipid antibodies

Fundamento y objetivo: Los anticuerpos antifosfolipídicos (AAF) aparecen con frecuencia asociados al lupus eritematoso sistémico (LES), con lo que aumenta el riesgo de trombosis. El objetivo del presente trabajo ha sido analizar el perfil temporal y los factores de riesgo de accidentes trombóticos en pacientes con LES. Pacientes y método: Se ha realizado un estudio retrospectivo en 102 pacientes con LES controlados en nuestra unidad ­edad media de 37,5 años (extremos, 8-85); 90 mujeres­, con una mediana de seguimiento de 72 meses (extremos, 9-324). Del total de la muestra, 41 (40,2%) presentaban AAF positivos. La probabilidad de presentar un accidente trombótico durante el seguimiento se calculó utilizando el método de Kaplan-Meier, y los factores asociados a este riesgo se determinaron según el método de riesgo proporcional de Cox. Resultados: Se registraron 13 accidentes trombóticos en el grupo de pacientes con AAF positivos (mediana de seguimiento, 83,5 meses) y 5 en el grupo con AAF negativos (mediana de seguimiento, 72 meses). La tasa de aparición de episodios fue de 3,93 y 0,96/100 pacientes/año, respectivamente. Las curvas de riesgo demostraron que los pacientes con LES y AAF tenían un elevado riesgo de trombosis desde el inicio y éste se mantenía a lo largo de los años. La presencia de un tiempo de tromboplastina parcial activada superior a 37 s fue el factor asociado significativamente al riesgo de accidentes trombóticos (test de rangos logarítmicos = 0,003), en estrecha relación con la positividad del anticoagulante lúpico. Los pacientes con proteinuria superior a 2,5 g/día y aquellos con anticoagulante lúpico también mostraron mayor tendencia a presentar trombosis. Conclusiones: En pacientes con LES y AAF positivos el riesgo de un primer episodio trombótico se mantiene sin cambios a lo largo de los años, y la determinación del tiempo de tromboplastina parcial activada fue el factor más determinante para el desarrollo de accidentes trombóticos

Background and objective: Antiphospholipid antibodies (aPL) are frequently associated with eritematosus systemic lupus (SLE) and increases the risk of thrombosis. The aim of the study was to analize risk factors of thrombosis and its temporal profile in subjects with SLE. Patients and method: One hundred and two SLE patients ­mean age: 37.5 years (range: 8-85); 90 women; mean of follow-up: 72 months (range: 9-324); 41 (40.2%) with aPL positive­ were included in the study. Actuarial Kaplan-Meier curves were used to assess the thrombosis risk and Cox proportional hazard model was used to evaluate factors associated with the risk. Results: 13 thrombotic events occurred in the group with aPL positive (mean of follow up: 83.5 months) and 5 events in aPL negative group (mean of follow up: 72 months). The event-rates were 3.93 and 0.96/100 patients/year for each group, respectively. Survival curves showed a significantly higher risk of thrombotic events in the patients with positive aPL as compared to the aPL negative group, and the risk still present throughout the observational time. Activated partial thromboplastine time up to 37 s was significantly associated with thrombosis risk (p = 0.003). Furthermore, positivity of lupus anticoagulant and proteinuria > 2,5 g/day tended to increase thrombotic risk, although they did not achieve statistical significance. Conclusions: In patients with SLE and aPL, risk of first thrombosis remains over the years, and a large activated partial thromboplastine time was the most important risk factor

Long-term prospective study of recurrent venous thromboembolism in patients younger than 50 years.

Long-term incidence of recurrent venous thromboembolism (VTE) in patients younger than 50 years, not affected by a malignancy or chronic diseases, are poorly characterized. After the initial episode of VTE and cessation of oral anticoagulation, 98 patients, mean age 32.2+/-9.2 years were followed for a median of 117 months (range 6-165). Congenital risk factors for VTE were present in 36% of patients, acquired persistent (positive antiphospholipid antibodies during the whole follow-up) in 19%, and acquired transitory in 44%. Thirty episodes of recurrent VTE were documented. The cumulative incidence of VTE after 1 year of follow-up was 5.1%, 9.8% after 2 years, 14% after 4 years, and 34.2% after 8 years. In the univariate analysis, the relative risk of recurrent VTE was 2.66 [95% confidence interval (CI) 1.03-6.90] for congenital risk factors, 4.97 (95% CI 1.75-14.0) for persistent acquired (antiphospholipid antibodies), 2.64 (95% CI 1.23-5.66) for male gender and 2.27(1.00-5.15) for body mass index>30 kg/m2. In the multivariate analysis, male gender [hazard ratio (HR) 4.23, 95% CI 1.88-9.77) the presence of congenital factors (HR 3.28, 95% CI 1.25-8.63) and acquired persistent factors (HR 8.50, 95% CI 2.84-25.50) were independent risk factors for recurrent VTE. In patients under 50 years of age without malignancy or underlying chronic disease, hospitalized for an acute thromboembolic event, the presence of antiphospholipid antibodies, congenital defects of coagulation, male sex, and obesity were risk factors for recurrent VTE. These data raise the possibility that selected patients with VTE may require prolonged anticoagulation to prevent recurrent disease.

[Risk factors and clinical characteristics of thromboembolic venous disease in young patients: a prospective study]. / Estudio prospectivo de los factores de riesgo y las características clínicas de la enfermedad tromboembólica en pacientes jóvenes.

BACKGROUND AND OBJECTIVE: We aimed to determine the risk factors of thromboembolic disease in young patients and to study the clinical characteristics according to the etiology. PATIENTS AND METHOD: A prospective study of 100 patients under 50 years who were not affected by neoplasias or chronic diseases and who required hospitalization due to thromboembolic disease. The morphological diagnosis was performed by eco-Doppler, flebography, lung gammagraphy or CT scan. Risk factors assessed were antithrombin, protein C and S deficiency, presence of factor V Leiden, prothrombin G20210A, hyperhomocisteinemia, increased PAI-I, increased factor VIII, and presence of antiphospholipid antibodies (APAs). Acquired factors were also evaluated. RESULTS: In 87% of patients, a venous thrombosis was observed in lower limbs. 37% of patients had congenital risk factors and 19% had APAs, whereas in the remaining patients only acquired factors were demonstrated. Most frequent congenital factors were factor V Leiden, pothrombin G20210A, and protein C and S deficiency. Most patients presented several risk factors. A family thrombotic history was significantly more frequent in the group with congenital risk factors. CONCLUSIONS: In 56% of young patients with thromboembolic disease, a congenital etiology or APAs are identified. In these patients the number of acquired factors needed to trigger thrombosis is fewer than in patients in whom a cause is not identified.