Sulodexide in venous disease Carroll, B J; Piazza, G; Goldhaber, S Z
Journal of thrombosis and haemostasis,
01/2019, Letnik:
17, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Sulodexide is a glycosaminoglycan extracted from porcine intestinal mucosa. The purpose of this review is to discuss sulodexide's complex pharmacological profile and its clinical applications for ...venous disease. Sulodexide has wide-ranging biological effects on the vascular system, including antithrombotic, profibrinolytic, anti-inflammatory, endothelial protective and vasoregulatory effects. Sulodexide has emerged as a potential therapeutic option for the management of chronic venous insufficiency, including venous ulceration, and the prevention of recurrent venous thromboembolism, with a low rate of major bleeding complications. Sulodexide's pleiotropic vascular effects may facilitate the management of common venous disorders.
Pulmonary embolism (PE) remains poorly understood. Rates of clinical outcomes such as death and recurrence vary widely among trials. We therefore established the International Cooperative Pulmonary ...Embolism Registry (ICOPER), with the aim of identifying factors associated with death.
2454 consecutive eligible patients with acute PE were registered from 52 hospitals in seven countries in Europe and North America. The primary outcome measure was all-cause mortality at 3 months. The prognostic effect of baseline factors on survival was assessed with multivariate analyses.
2110 (86·0%) patients had PE proven by necropsy, high-probability lung scan, pulmonary angiography, or venous ultrasonography plus high clinical suspicion; ICOPER accepted without independent review diagnoses and interpretation of imaging provided by participating centres; 3-month follow-up was completed in 98·0% of patients. The overall crude mortality rate at 3 months was 17·4% (426 of 2454 deaths, including 52 patients lost to follow-up): 179 of 397 (45·1%) deaths were ascribed to PE and 70 of 397 (17·6%) to cancer, and no information on the cause of death was available for 29 patients. After exclusion of 61 patients in whom PE was first discovered at necropsy, the mortality rate at 3 months was 15·3% (365 of 2393 deaths). On multiple-regression modelling, age over 70 years (hazard ratio 1·6 95% Cl 1·1–2·3), cancer (2·3 1·5–3–5), congestive heart failure (2·4 1·5–3·7), chronic obstructive pulmonary disease (1·8 1·2–2–7), systolic arterial hypotension (2·9 1·7–5·0), tachypnoea (2·0 1·2–3·2), and right-ventricular hypokinesis on echocardiography (2·0 1·3–2·9) were identified as significant prognostic factors.
PE remains an important clinical problem with a high mortality rate, Data from ICOPER provide rates and highlight adverse prognostic categories that will help in planning of future trials of high-risk PE patients.
A growing health problem, venous thromboembolism (VTE), including pulmonary embolism (PE) and deep vein thrombosis (DVT), requires refined diagnostic and therapeutic approaches. Neutrophils ...contribute to thrombus initiation and development in experimental DVT. Recent animal studies recognized neutrophil extracellular traps (NETs) as an important scaffold supporting thrombus stability. However, the hypothesis that human venous thrombi involve NETs has not undergone rigorous testing.
To explore the cellular composition and the presence of NETs within human venous thrombi at different stages of development.
We examined 16 thrombi obtained from 11 patients during surgery or at autopsy using histomorphological, immunohistochemical and immunofluorescence analyses.
We classified thrombus regions as unorganized, organizing and organized according to their morphological characteristics. We then evaluated them, focusing on neutrophil and platelet deposition as well as micro-vascularization of the thrombus body. We observed evidence of NET accumulation, including the presence of citrullinated histone H3 (H3Cit)-positive cells. NETs, defined as extracellular diffuse H3Cit areas associated with myeloperoxidase and DNA, localized predominantly during the phase of organization in human venous thrombi.
NETs are present in organizing thrombi in patients with VTE. They are associated with thrombus maturation in humans. Dissolution of NETs might thus facilitate thrombolysis. This finding provides new insights into the clinical development and pathology of thrombosis and provides new perspectives for therapeutic advances.
Rapid, noninvasive, and accurate prognostic assessment with an inexpensive cardiac biomarker is an appealing approach for patients with acute pulmonary embolism (PE).
We measured at the time of ...admission the plasma level of plasma brain natriuretic peptide (BNP) to determine its utility in prognosticating the clinical course of 73 consecutive patients with acute PE. We used a prespecified BNP cut-off level (<90 pg/mL) for the prediction of the absence of a major adverse cardiovascular event, defined as any of the following: death, cardiopulmonary resuscitation, mechanical ventilation, or use of pressors, thrombolysis, catheter fragmentation, or surgical embolectomy. In the 20 (27%) patients with adverse events, median BNP (194.2, range 3.7 to 1201.1 pg/mL) was higher than in patients with a benign course (39.1, range 1.0 to 1560.0 pg/mL; P<0.001). However, 3 patients with adverse outcomes had low BNP levels on admission: 1 death, BNP 52 pg/mL; 1 patient with prolonged cardiopulmonary resuscitation, BNP 3.7 pg/mL; and 1 patient undergoing rescue thrombolysis, BNP 75 pg/mL. Sensitivity, specificity, and negative and positive predictive value of BNP levels <90 pg/mL for absence of adverse outcomes were 85% (64% to 95%), 75% (62% to 85%), 93% (95% CI 81% to 98%), and 57% (39% to 73%), respectively. The optimal BNP cut-off level, identified by receiver operating characteristic analysis, was <50 pg/mL.
Low BNP levels do not guarantee an uncomplicated hospital course in patients with acute PE, using a "congestive heart failure" cut-off level of 90 pg/mL. A lower cut-off level of <50 pg/mL identifies 95% of patients with a benign clinical course.
Four-factor prothrombin complex concentrates (PCCs), which contain factor II, FVII, FIX, and FX, have shown the potential to reverse the anticoagulant effect of rivaroxaban in healthy volunteers. The ...purpose of this study was to determine whether a three-factor PCC, which contains little FVII, has a similar effect.
We performed an open-label, single-center, parallel-group study comparing the effect of a three-factor PCC (Profilnine SD) with that of a four-factor PCC (Beriplex P/N) on the pharmacodynamics of rivaroxaban in 35 healthy volunteers. After receiving 4 days of rivaroxaban 20 mg twice daily to obtain supratherapeutic steady-state concentrations, volunteers were randomized to receive a single 50 IU kg(-1) bolus dose of four-factor PCC, three-factor PCC or saline 4 h after the morning dose of rivaroxaban on day 5, and the effects of these interventions on prothrombin time and thrombin generation were determined. Within 30 min, four-factor PCC reduced mean prothrombin time by 2.5-3.5 s, whereas three-factor PCC produced only a 0.6-1.0-s reduction. In contrast, three-factor PCC reversed rivaroxaban-induced changes in thrombin generation more than four-factor PCC.
This study demonstrates the potential of both three-factor and four-factor PCCs to at least partially reverse the anticoagulant effects of rivaroxaban in healthy adults. The discrepant effects of the PCC preparations may reflect differences in the procoagulant components present in each.
Considerable variability exists in the use of pharmacological thromboprophylaxis among acutely ill medical patients, partly because clinically relevant end points have not been fully assessed in this ...population. We undertook an international, multicenter, randomized, double-blind, placebo-controlled trial using clinically important outcomes to assess the efficacy and safety of dalteparin in the prevention of venous thromboembolism in such patients.
Patients (n=3706) were randomly assigned to receive either subcutaneous dalteparin 5000 IU daily or placebo for 14 days and were followed up for 90 days. The primary end point was venous thromboembolism, defined as the combination of symptomatic deep vein thrombosis, symptomatic pulmonary embolism, and asymptomatic proximal deep vein thrombosis detected by compression ultrasound at day 21 and sudden death by day 21. The incidence of venous thromboembolism was reduced from 4.96% (73 of 1473 patients) in the placebo group to 2.77% (42 of 1518 patients) in the dalteparin group, an absolute risk reduction of 2.19% or a relative risk reduction of 45% (relative risk, 0.55; 95% CI, 0.38 to 0.80; P=0.0015). The observed benefit was maintained at 90 days. The overall incidence of major bleeding was low but higher in the dalteparin group (9 patients; 0.49%) compared with the placebo group (3 patients; 0.16%).
Dalteparin 5000 IU once daily halved the rate of venous thromboembolism with a low risk of bleeding.
Treatment of venous thromboembolism (VTE) in patients with cancer has a high rate of recurrence and bleeding complications. Guidelines recommend low-molecular-weight heparin (LMWH) for at least 3-6 ...months and possibly indefinitely for patients with active malignancy. There are, however, few data supporting treatment with LMWH beyond 6 months. The primary aim of the DALTECAN study (NCT00942968) was to determine the safety of dalteparin between 6 and 12 months in cancer-associated VTE.
Patients with active cancer and newly diagnosed VTE were enrolled in a prospective, multicenter study and received subcutaneous dalteparin for 12 months. The rates of bleeding and recurrent VTE were evaluated at months 1, 2-6 and 7-12.
Of 334 patients enrolled, 185 and 109 completed 6 and 12 months of therapy; 49.1% had deep vein thrombosis (DVT); 38.9% had pulmonary embolism (PE); and 12.0% had both on presentation. The overall frequency of major bleeding was 10.2% (34/334). Major bleeding occurred in 3.6% (12/334) in the first month, and 1.1% (14/1237) and 0.7% (8/1086) per patient-month during months 2-6 and 7-12, respectively. Recurrent VTE occurred in 11.1% (37/334); the incidence rate was 5.7% (19/334) for month 1, 3.4% (10/296) during months 2-6, and 4.1% (8/194) during months 7-12. One hundred and sixteen patients died, four due to recurrent VTE and two due to bleeding.
Major bleeding was less frequent during dalteparin therapy beyond 6 months. The risk of developing major bleeding complications or VTE recurrence was greatest in the first month of therapy and lower over the subsequent 11 months.
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