Progression Of Chronic Venous Insufficiency Research Articles

Anatomical-functional state of surface lymphatic system of lower extremities in chronic vein diseases according to fluorescence lymphograph

Despite the large arsenal of diagnostic methods for studying the lymphatic system, there are isolated works on its morpho-functional state in chronic venous insufluciency. The purpose of the study was to study the anatomical and physiological state of the surface lymphatic system of the lower extremities in persons with different clinical classes of chronic vein diseases using fluorescence lifography. The study was conducted in 105 patients divided into six groups according to the clinical class of chronic diseases of the veins of the lower extremities according to the CEAP classiffication. We used fluorescent lymphography using sodium fluorescein to study the anatomical and functional capabilities of the lymphotone. The study revealed that morphofunctional changes in superficial lymphatic vessels in chronic lower extremity vein diseases depend on venous system decompensation. With an increase in the clinical class of chronic diseases of the veins of the lower extremities, the rate of lymph flow through the superficial lymphatic vessels is statistically significantly reduced. At the same time, the antegrade lymph cell is completely absent in С5-С6, with the appearance of retrograde outflow and discharge of the lymph into the deep lymph vessels. Thus, the progression of chronic venous insufficiency leads to proportional progression of morphofunctional changes in the superficial lymphatic system, which leads to the formation of lymphovenous insufficiency.

The Role of the Vegfa C936t Polymorphism in the Development of Chronic Venous Insufficiency of the Legs And Its Analysis

In 98 patients, an analysis of the genetic risk factor for the development of chronic venous insufficiency was carried out by studying the frequency of distribution of alleles and genotypes of the C936T polymorphism in the VEGFA gene. In both groups, the actual distribution of C807T polymorphism genotypes corresponded to those expected under the Hardy-Weinberg equilibrium (p
 <0.05). A significant relationship was established between the risk of developing chronic venous insufficiency and the distribution of predisposing/protective variants of the C807T polymorphism genotypes in the VEGFA gene. These data allow us to suggest testing this locus to predict the risk of occurrence and progression of chronic venous insufficiency>

No More Venous Ulcers-What More Can We Do?

Venous leg ulcers (VLUs) are the most severe complication caused by the progression of chronic venous insufficiency. They account for approximately 70-90% of all chronic leg ulcers (CLUs). A total of 1% of the Western population will suffer at some time in their lives from a VLU. Furthermore, most CLUs are VLUs, defined as chronic leg wounds that show no tendency to heal after three months of appropriate treatment or are still not fully healed at 12 months. The essential feature of VLUs is their recurrence. VLUs also significantly impact quality of life and could cause social isolation and depression. They also have a significant avoidable economic burden. It is estimated that the treatment of venous ulceration accounts for around 3% of the total expenditure on healthcare. A VLU-free world is a highly desirable aim but could be challenging to achieve with the current knowledge of the pathophysiology and diagnostic and therapeutical protocols. To decrease the incidence of VLUs, the long-term goal must be to identify high-risk patients at an early stage of chronic venous disease and initiate appropriate preventive measures. This review discusses the epidemiology, socioeconomic burden, pathophysiology, diagnosis, modes of conservative and invasive treatment, and prevention of VLUs.

[The marginal vein-Still a rare entity: case series of 16 patients].

HintergrundDie Marginalvene (MV) ist eine angeborene, vorwiegend venöse Gefäßmalformation, die auf einer fehlenden Rückbildung des embryonalen Venensystems an den unteren Extremitäten beruht. Sie geht mit einer Vielzahl an Komplikationen einher. Bisher werden in der Literatur keine einheitlichen Therapieregime beschrieben.FragestellungWelche Behandlungsstrategien und Ergebnisse gibt es bei Patienten mit MV?Material und MethodenIm Zeitraum 01.01.2008 bis 31.12.2020 wurden alle am Universitätsklinikum Augsburg behandelten Patienten mit Marginalvene retrospektiv aufgearbeitet.ErgebnisseDas mediane Alter zum Diagnosezeitpunkt lag bei 14,8 Jahren (3–42 Jahre). 12/16 Patienten hatten eine Beinlängendifferenz. 75 % der Patienten (12/16) hatten bereits zur Diagnosestellung MV eine chronisch-venöse Insuffizienz (CVI). Im untersuchten Kollektiv wurden 62,5 % (10/16) der Patienten zum Zeitpunkt der Diagnosestellung mittels Kompression konservativ behandelt. Bei weiteren 31,3 % (5/16) der Patienten erfolgte primär eine offen-chirurgische Entfernung der MV und bei 1/16 Patienten wurde die MV primär mittels endovenöser Lasertherapie (EVLT) verschlossen; 15/16 Patienten wurden sekundär therapiert. 2,6 ± 2,4 (MW ± SD) Sekundärprozeduren wurden pro Patient im Follow up durchgeführt. Das mittlere Follow-up lag bei 8,1 Jahren.DiskussionZur Prävention/Vermeidung einer Progression einer CVI und Thrombembolieprophylaxe sollte nach Diagnosestellung die MV zeitnah verschlossen/entfernt werden. Die Anwendung chirurgisch-konventioneller Techniken zur Entfernung der MV scheint gegenüber der Behandlung mit minimal-invasiven Prozeduren hinsichtlich der Anzahl der erforderlichen Sekundäreingriffe von Vorteil.

Time course of microvalve pathophysiology in high pressure low flow model of venous insufficiency and the role of micronized purified flavonoid fraction.

The aim of this study was to characterize, in an experimental model, the mechanisms involved in the initiation of venous insufficiency at the level of microvenous valve and whether they can be influenced by early treatment with micronized purified flavonoid fraction (MPFF). The external right iliac vein of 78 male golden Syrian hamsters was ligated to induce chronic venous insufficiency. Internal venular diameter as well as leukocyte-endothelium-interaction (leukocytes sticking after staining with rhodamine 6G), were assessed using an intravital microscope. In the second part of the study 30 animals were divided into three groups and underwent: ligation plus MPFF, ligation plus 10% lactose solution (vehicle), or sham operation. Treatment with MPFF 100 mg/kg/day or vehicle started 2 days before ligation and lasted for 7 days. Venular diameter and number of adherent leukocytes were assessed 5 days post-ligature. Venular diameter increased immediately after ligature and reached a maximum at 4 hours (P<0.001 vs. baseline), followed by a plateau before gradually returning to baseline dimensions. The increase in the number of adherent leukocytes was also immediate but attained maximal number at 3 days (P<0.0001), followed by a plateau and then gradual return to baseline numbers. In MPFF-treated animals, leukocyte adhesion to the microvalves was prevented compared with vehicle-treated animals (P<0.0001) and venular diameter was also significantly reduced (P<0.05). Venous hypertension induced immediate venular dilatation followed by an increase in the number of adherent leukocytes at microvalve level. Treatment with MPFF prevented the initiation of microvalve inflammation and may play a protective role in the progression of chronic venous insufficiency.

[Connection of perforating and intramuscular veins of the crus in varicosity].

This study was undertaken to investigate the clinical anatomy of indirect perforating veins and their connection to the intramuscular venous collector of the crus by means of MSCT phlebography. From 2015 till now, MSCT phlebography was used to examine a total of 400 patients with chronic diseases of lower limb veins. According to the CEAP classification, clinical class C0-C1 was present in 108 (27%) subjects, C2-C3 - in 173 (43.3%) patients, and C4-C6 - in 119 (29.7%) patients. All examinations were performed using a 128-slice multispiral CT scanner Philips Ingenuity, followed by 3D reconstruction with the help of the IntelliSpace Portal Image Editing Software package. In the 400 extremities examined, we identified a total of 11 655 indirect perforating veins of the calf. Studying the anatomical localization of perforating veins demonstrated that 3248 veins belonged to the posterior tibial group, 1830 veins - to the lateral group, 873 veins - to the paraachillary group, 276 veins - to the intergemellary group, 4451 veins - to the medial group, and 997 perforating veins - to the lateral group. 3D imaging made it possible to trace the entire course of the perforating veins originating from the posterior arched, intersaphenous, oblique veins or other communicating branches to the subfascial and intramuscular portions to the connection with the gastrocnemius and soleus veins which as the disease progresses undergo ectasia with the formation therein of pathological segmental hypervolemia. Studying the ratio of the revealed indirect perforating veins of the determined groups and the presence of gradually developing ectasia of the intramuscular venous collectors in patients of various clinical classes from C0-C1 to C4-C6 made it possible to draw a conclusion on the involvement of perforating veins and intramuscular veins of the crus into the common pathohaemodynamic circle of the development and progression of chronic venous insufficiency in patients with varicose veins.

SURGICAL TREATMENT OF COMPLICATED FORMS OF CHRONIC VENOUS INSUFFICIENCY IN LOWER LIMBS (REVIEW ARTICLE)

Venous diseases of the lower limbs that are accompanied by the development of trophic ulcers are among the medical and social challenges. The vast number of patients is in working age, from 30 to 65 years old. Severe forms of the disease are registered in 27% of the cases; active or healed trophic ulcers are diagnosed in 12.9 % of cases. At present special attention is being paid to the effective surgical treatment of the pathology, to the introduction of the latest surgical interventions, which provide complete radicalism about the causes of trophic ulcers of venous genesis and ensure the maximum cosmetic effect. The aim of this work is to analyze the scientific literature on using the latest surgical techniques in the treatment of venous pathology in patients with trophic ulcers of lower extremities to promote improving the existing and elaborate new surgical interventions in terms of this pathology. Nowadays surgical treatment of patients with chronic venous insufficiency of the lower extremities, especially in case of trophic leg ulcers can be considered as the stage of the integrated treatment of venous trophic disorders. Modern surgical interventions differ in the methods, techniques and tools used, but provide the maximum cosmetic effect and complete radicalism regarding the causes of chronic venous insufficiency. Correction of pathological venous-venous reflux is the main method of eliminating venous hypertension, which underlies the progression of chronic venous insufficiency and promotes the development of trophic disorders, including the ulcers formation. The etiological cause of venous trophic ulcer is the appearance of pathological reflux, which occurs in the superficial, deep and perforating veins and, accordingly, the place of surgery should be those venous segments in which the pathological process is diagnosed. The operation can be performed simultaneously or in two stages: first, the vertical venous-venous reflux is eliminated, followed by the correction of the horizontal reflux. When using modern minimally invasive technologies, adequate and complete correction of venous blood flow in the affected limb is performed simultaneously producing no serious tissue damages to avoid cosmetic effect and to lessen postoperative period. Thus, the analysis of the scientific literatures has shown the unity of views on the strategy of surgical treatment of varicose trophic ulcers that involves the elimination of vertical and horizontal reflux, but the absence of views unity on tactical approaches in solving these issues.

Degradation of lymphatic anatomy and function in early venous insufficiency

ObjectiveWe used near-infrared fluorescence lymphatic imaging in a pilot study to assess the lymphatics in preulcerative (C2-C4) venous insufficiency and determine whether involvement and/or degradation of lymphatic anatomy or function could play a role in the progression of chronic venous insufficiency. We also explored the role of lymphatics in early peripheral arterial disease. MethodsAfter informed consent and intradermal injections of indocyanine green for rapid lymphatic uptake, near-infrared fluorescence lymphatic imaging was used to assess the lymphatic anatomic structure and quantify the lymphatic propulsion rates in subjects with early venous insufficiency. The anatomic observations included interstitial backflow, characterized by the abnormal spreading of indocyanine green from the injection site primarily into the surrounding interstitial tissues; dermal backflow, characterized by the retrograde movement of dye-laden lymph from collecting lymphatics into the lymphatic capillaries; and lymphatic vessel segmentation and dilation. ResultsTen subjects with venous insufficiency were enrolled, resulting in two legs with C2 disease, nine legs with C3 disease, eight legs with C4 disease, and one leg with C5 disease. Interstitial and/or dermal backflow were observed in 25%, 33%, and 41% of the injection sites in each limb with C2, C3, and C4 disease, respectively. Distinct vessel segmentation and dilation were observed in limbs with a C3 and higher classification, and dermal backflow proximal to the injection sites was observed in two legs with C4 disease and in the inguinal region of the C5 study subject. The overall average lymph propulsion rates were 1.3 ± 0.4, 1.2 ± 0.7, and 0.8 ± 0.5 contractile events/min for limbs with C2, C3, and C4 disease, respectively. One subject with peripheral arterial disease, who had previously undergone bypass surgery, presented with extensive dermal backflow and lymphatic reflux. ConclusionsNear-infrared fluorescence lymphatic imaging demonstrated that, compared with normal health subjects, the lymphatic anatomy and contractile function generally degrade with the severity of venous insufficiency. Lymphatic abnormalities mimic those in early cancer-acquired lymphedema subjects, as previously observed by us and others. Additional studies are needed to decipher the relationship, including any causality, between lymphatic dysfunction and peripheral vascular disease and venous insufficiency.

[Prophylaxis of Recurrent Venous Leg Ulcer].

Venous leg ulcer (VLU) counts among the most common chronic wounds in Europe. Treatment is lengthy, cumbersome and costly, and there is a high rate of recurrence. This review shows the measures that should be offered to every patient with healed VLU to permanently prevent recurrence. To prevent VLU in case of varicose veins, the progression of chronic venous insufficiency (CVI) has to be stopped. There is convincing evidence that the effective treatment of varicose veins reduces the recurrence rate in patients with VLU. In patients with post-thrombotic syndrome (PTS), further thrombosis should be prevented through targeted prophylaxis of new thromboembolic events. The benefit of endovascular revascularization on the VLU recurrence rate in patients with post-thrombotic damage in the pelvic veins has not been proven in clinical studies. On the other hand, it has been clearly demonstrated in several studies that compression therapy is the basic procedure for the prevention of recurrent VLU in patients with varicose veins or PTS, regardless of whether other measures have been implemented or not. Good adherence in patients with compression therapy is more important than choosing the highest possible compression class. Future efforts for patients with VLU must aim to provide therapists with tools and treatment strategies to guide their patients and to increase patients' acceptance and understanding of the importance of self-management, in particular regarding compression therapy for the prevention of recurrent VLU.

Long-term results of the monocusp valve formation in the common femoral vein in patients with avalvular deep veins of the lower extremities.

Aim of the study was to evaluate the long-term results of the monocusp valve formation in the common femoral vein (CFV) in patients with avalvular deep veins (ADV) of the lower extremities. A total of 36 patients (24 women and 12 men) at the age varying from 37 to 58 years old were given surgical treatment during the period from 2008 to 2014. Six patients presented with congenital ADV, while the remaining 30 ADV had a consequence of the post-thrombotic lesion in the valves with the complete recanalization and manifested deep venous axial reflux. In terms of CEAP clinical classification, the patients were categorized into the following groups: С4b (N.=11), C5 (N.=18), C6 (N.=7). All the patients underwent Duplex ultrasound (DUS) examination. Twelve patients were additionally examined by venography. Kistner grade IV reflux was diagnosed in all the patients. Twenty-eight patients had undergone surgical interventions on superficial and perforating veins before. The severe (C4b-C6) forms of chronic venous disease with manifested axial reflux in deep veins were regarded as an indication for surgery in the patients refractory to traditional treatment. The method described by Opie et al. was employed to construct the monocusp venous valve in the CFV. The long-term results of the treatment were evaluated in 26 patients followed up during the period from 18 to 48 (mean 29.5±8.2) months. Cumulative clinical success rate at four years was 76.5%. Freedom from ulcer recurrence at four years was 83.4% (C6 patients). Cumulative competence rate of the neovalve was accomplished in 70.6%. The evaluation in two years based on the VCSS revealed the reduction in the severity of the manifestations of chronic venous insufficiency (P<0.01). The quality of life was improved, its index decreased from 60.6±18.7 to 40.7±12.8 (P<0.05). The circumference of the narrowest segment of the tibia decreased from 271.1±4.7 to 256.8±5.7 mm (P<0.05). Formation of the monocusp valve in CFV makes it possible to eliminate pathological blood reflux from the inferior vena cava to deep veins of the lower extremities that is known to be one of the main factors in the appearance and progression of chronic venous insufficiency (CVI). The high effectiveness of this operation is confirmed by the well apparent clinical improvement in the state of the affected lower extremity and the quality of life of the patients.

A plasma oxidative stress global index in early stages of chronic venous insufficiency

Chronic venous insufficiency (CVI) represents a social and health care problem because it affects working age populations, particularly in jobs requiring orthostasis, has no effective pharmacologic treatment, and requires surgery. Oxidative stress is present in varicose veins, but whether this is reflected in the plasma is controversial. We aimed to quantify plasma oxidative stress biomarkers in the early stages of CVI and calculate a global index of oxidative stress representative of the disease. Plasma was obtained from blood samples of nine patients with CEAP C2 stage CVI and 10 healthy controls. Biomarkers related to antioxidant defense systems (total thiols, reduced glutathione, uric acid, total antioxidant capacity, catalase), oxidative damage (malondialdehyde-bound protein, protein carbonyls, advanced oxidation products, and 3-nitrotyrosine), and activity of enzymes producing key free radicals (xanthine oxidase and myeloperoxidase) were assessed. Compared with the controls, CVI patients exhibited decreased catalase activity and thiol levels and increased malondialdehyde-bound protein and protein carbonyls. These parameters were used to calculate the global index of oxidative stress in CVI, which was significantly different between groups. It is possible to detect significant changes in plasma oxidative stress biomarkers in early stages of CVI and to calculate a global index representative of the oxidative status in an individual. This index, with the appropriate validation in a larger population, could be used for early detection or progression of CVI.

Predictive Values in the Progression of Chronic Venous Insufficiency Associated with Superficial Venous Incompetence.

The purpose of this study was to define predictive values in the progression of chronic venous insufficiency in patients with isolated superficial venous incompetence using duplex ultrasound and air plethysmography (APG). Five hundred eight legs in 371 patients with isolated superficial venous incompetence were included in this study. A color duplex scanner with a 5- to 10-MHz linear transducer was used to assess the distribution and the extent of venous reflux as well as the duration of reflux and the retrograde peak velocity at the saphenofemoral junction, greater saphenous vein in the thigh, and the saphenopopliteal junction. Venous reflux was considered to be present if the duration of reflux was greater than 0.5 s. The extent of greater saphenous vein is divided into 3 types. Type I: reflux from the groin to the ankle. Type II: reflux from the groin to the below-knee level. Type III: reflux from the groin to the above-knee level. Values obtained by APG were the venous volume (VV), venous filling index (VFI), ejection fraction (EF), and residual venous fraction (RVF). Between-group differences were analyzed using Wilcoxon's nonparametric rank sum test. Type I limbs had highest incidence of advanced chronic venous symptoms. Based on the duplex-derived duration of reflux and retrograde peak velocity in Type I limbs, there were three major groups: limbs with a retrograde peak velocity greater than 30 cm/s and a duration of reflux less than 3 s (group A), limbs with a retrograde peak velocity greater than 30 cm/s and a duration of reflux greater than 3 s (group B) and limbs with a retrograde peak velocity of less than 30 cm/s and a duration of reflux greater than 3 s (group C). Most of the class 2 and class 3 limbs belonged to Group C, whereas most of the class 4 limbs and all of the class 5 and class 6 limbs belonged to group A and group B. APG-derived VFI had significantly higher values in group A and group B compared with group C (P < 0.002). Peak velocity greater than 30 cm/s had a high positive predictive value of 75.0% with a sensitivity of 91.1%. Although duplex-derived duration of reflux is widely used to assess venous reflux, our data suggest that the peak velocity is a better predictor of the progression of chronic venous insufficiency and that it correlates well with the severity of the clinical manifestation in cases with isolated superficial venous insufficiency.

Transforming growth factor β1 secretion and receptor expression are dysregulated with the progression of chronic venous insufficiency

Transforming growth factor β1 secretion and receptor expression are dysregulated with the progression of chronic venous insufficiency

Recommended reporting standards for endovenous ablation for the treatment of venous insufficiency: Joint Statement of the American Venous Forum and the Society of Interventional Radiology

Lower extremity venous insufficiency is a common medical condition that afflicts approximately 25% of women and 15% of men.1Callam M.J. Epidemiology of varicose veins.Br J Surg. 1994; 81: 167-173Crossref PubMed Scopus (533) Google Scholar Great saphenous vein (GSV) reflux is the most common underlying cause of symptomatic varicose veins. An increasingly popular alternative to traditional surgical stripping of the GSV for management of saphenous vein reflux is endovenous ablation (EVA) of that vein using laser energy, radiofrequency-generated thermal energy, or a chemical sclerosant.2Bone C. Tratamiento endoluminal delas vaarices con laser de diodo: studio preliminary.Rev Patol Vasc. 1999; 5: 35-46Google Scholar, 3Min R.J. Khilnani N. Zimmet S.E. endovenous laser treatment of saphenous vein reflux: long term results.J Vasc Interv Radiol. 2003; 14: 991-996Abstract Full Text Full Text PDF PubMed Scopus (514) Google Scholar, 4Chandler J.G. Pichot O. Sessa C. Schuller-Petrovic S. Osse F.J. Bergan J.J. Defining the role of extended saphenofemoral junction ligation: a prospective comparative study.J Vasc surg. 2000; 32: 941-953Abstract Full Text Full Text PDF PubMed Scopus (138) Google Scholar, 5Merchant R.F. DePalma R.G. Kabnick L.S. Endovascular obliteration of saphenous reflux: a multi-center study.J Vasc Surg. 2002; 35: 1190-1196Abstract Full Text Full Text PDF PubMed Scopus (235) Google Scholar, 6Pichot O. Sessa C. Chandler J.G. Nuta M. Perrin M. Role of duplex imaging in endovenous obliteration for primary venous insufficiency.J Endovasc Ther. 2000; 7: 451-459Crossref PubMed Scopus (51) Google Scholar, 7Kabnick L.S. Merchant R.F. Twelve and twenty-four month follow-up after endovascular obliteration of saphenous vein reflux: a report from the multi-center registry.J Phlebol. 2001; 1: 17-24Google Scholar, 8Lurie F. Creton D. Eklof B. Kabnick L.S. Kistner R.L. Pichot O. Schuller-Petrovic S. Sessa C. Prospective randomized study of endovenous radiofrequency obliteration (closure procedure) versus ligation and stipping in a selected patient population (EVOLVeS Study).J Vasc Surg. 2003; 38: 207-214Abstract Full Text Full Text PDF PubMed Scopus (361) Google Scholar, 9Lurie F. Creton D. Eklof B. Kabnick L.S. Kistner R.L. Pichot O. et al.Prospective randomized study of endovenous radiofrequency obliteration (closure) versus ligation and vein stripping (EVOLVeS): two-year follow-up.Eur J Vasc Endovasc Surg. 2005; 29: 67-73Abstract Full Text Full Text PDF PubMed Scopus (291) Google Scholar Comparative studies evaluating long-term EVA clinical treatment outcomes, the optimal timing of adjunctive procedures, and the relative impact of anatomic location, size, length, and energy deposition in the treated segment are expected in the near future. This document provides recommended reporting standards for physicians performing clinical research studies evaluating EVA in the treatment of lower extremity venous reflux and is thereby expected to facilitate comparison between the results of different studies and to improve the overall quality of clinical research on venous disease. These standards have been developed by The Society of Interventional Radiology (SIR) and The American Venous Forum and were approved by the SIR Executive Council on February 28, 2007, and by the AVF Executive Council on February 13, 2007. The general description of the population from which studied groups were selected should be presented. This should include the total number of patients seen and treated at participating institutions during the study period, patients' gender and age distribution, and frequencies of major treatment modalities used. For studies including patients with bilateral disease, both the number of patients and the number of treated limbs, and whether limbs were treated concomitantly or staged must be stated. Baseline patient characteristics should include the level II basic CEAP10Eklof B. Rutherford R.B. Bergan J.J. Carpentier P.H. Gloviczki P. Kistner R.L. et al.American Venous Forum International Ad Hoc Committee for Revision of the CEAP ClassificationRevision of the CEAP classification for chronic venous disorders: consensus statement.J Vasc Surg. 2004; 40: 1248-1252Abstract Full Text Full Text PDF PubMed Scopus (1395) Google Scholar classification (Table I).Table ICEAP classification of chronic venous diseaseClassificationSymptomClinical C0No visible or palpable signs of venous disease C1Telangiectases or reticular veins C2Varicose veins C3Edema C4aPigmentation or eczema C4bLipodermatosclerosis or atrophie blanche C5Healed venous ulcer C6Active venous ulcer SSymptomatic, including ache, pain, tightness, skin irritation, heaviness, and muscle cramps, and other complaints attributable to venous dysfunction AAsymptomaticEtiologic EcCongenital EpPrimary EsSecondary (postthrombotic) EnNo venous cause identifiedAnatomic AsSuperficial veins ApPerforator veins AdDeep veins AnNo venous location identifiedPathophysiologic PrReflux PoObstruction Pr,oReflux and obstruction PnNo venous pathophysiology identifiableLevel of investigation Level IOffice visit, with history and clinical examination, which may include the use of a hand-held Doppler scanner. Level IINoninvasive vascular laboratory testing, which now routinely includes duplex color scanning, with some plethysmographic method added as desired Level IIIInvasive investigations or more complex imaging studies, including ascending and descending venography, venous pressure measurements, computed tomography, or magnetic resonance imaging.ExampleA patient has painful swelling of the leg, and varicose veins, lipodermatosclerosis, and active ulceration. Duplex scanning shows axial reflux of the great saphenous vein above and below the knee, incompetent calf perforator veins, and axial reflux in the femoral and popliteal veins. There are no signs of postthrombotic obstruction.Classification according to basic CEAP: C6,S, Ep, As,p,d, Pr. (2004-05-17, L II). Open table in a new tab Severity of the disease should be reported using validated scales. The Venous Clinical Severity Score (VCSS, Table II) is highly recommended as a measure of overall disease severity.11Rutherford R.B. Padberg Jr, F.T. Comerota A.J. Kistner R.L. Meissner M.H. Moneta G.L. Venous severity scoring: a adjunct to venous outcome assessment.J Vasc Surg. 2000; 31 (Jun): 1307-1312Abstract Full Text Full Text PDF PubMed Scopus (574) Google Scholar, 12Kakkos S.K. Rivera M.A. Matsagas M.I. Lazarides M.K. Robless P. Belcaro G. et al.Validation of the new venous severity scoring system in varicose vein surgery.J Vasc Surg. 2004; 39: 696-697Abstract Full Text Full Text PDF Google Scholar Use of both generic and venous disease-specific measures is the accepted standard for studying quality-of-life (QOL) changes. The Venous Insufficiency Epidemiologic and Economic Study of Quality-of-Life (VEINES-QOL/Sym) questionnaire scale, the Chronic Venous Insufficiency Questionnaire-2 (CIVIQ-2), and the Aberdeen questionnaires have all been validated in patients with lower extremity venous reflux and are highly recommended for use as venous disease–specific QOL measures.13Lamping D.L. Abenhaim L. Kurz X. Schroter S. Kahn S.R. Measuring quality of life and symptoms in chronic venous disorders of the leg: development and psychometric evaluation of the VEINES-QOL/Sym questionnaire.Qual Life Res. 1998; 7: 621-622Google Scholar, 14Lamping D.L. Schroter S. Kurz X. Kahn S.R. Abenhaim L. Evaluation of outcomes in chronic venous disorders of the leg: development of a scientifically rigorous, patient-reported measure of symptoms and quality-of-life.J Vasc Surg. 2003; 37: 410-419Abstract Full Text PDF PubMed Scopus (240) Google Scholar, 15Smith J.J. Guest M. Greenhalgh R.M. Davies A.H. Measuring the quality of life in patients with venous ulcers.J Vasc Surg. 2000; 31: 642-649Abstract Full Text Full Text PDF PubMed Scopus (139) Google Scholar, 16Franks P.J. Moffatt C.J. Health related quality of life in patients with venous ulceration: use of the Nottingham health profile.Qual Life Res. 2001; 10: 693-700Crossref PubMed Scopus (89) Google Scholar, 17Wiebe S. Guyatt G. Weaver B. Matijevic S. Sidwell C. Comparative responsiveness of generic and specific quality-of-life instruments.J Clin Epidemiol. 2003; 56: 52-60Abstract Full Text Full Text PDF PubMed Scopus (362) Google Scholar, 18Kahn S.R. Milan C.E. Lamping D.L. Kurz X. Bérard A. Abenhaim L.A. VEINES Study GroupRelationship between clinical classification of chronic venous disease and patient-reported quality of life: results from an international cohort study.J Vasc Surg. 2004; 39: 823-828Abstract Full Text Full Text PDF PubMed Scopus (135) Google Scholar, 19Launois R. Reboul-Marty J. Henry B. Construction and validation of a quality of life questionnaire in chronic lower limb venous insufficiency (CIVIQ).Qual Life Res. 1996; 5: 539-554Crossref PubMed Scopus (342) Google ScholarTable IIVenous Clinical Severity ScoreAttributeAbsent = 0Mild = 1Moderate = 2Severe = 3PainNoneOccasional, not restricting activity or requiring analgesicsDaily, moderate activity limitation, occasional analgesicsDaily, severe limiting activities or requiring regular use of analgesicsVaricose veinsNoneFew, scattered branch varicose veinsMultiple: GSV varicose veins confined to calf or thighExtensive: thigh and calf or GSV and SSV distributionVenous edemaNoneEvening ankle onlyAfternoon edema, above ankleMorning edema above ankle and requiring activity change, elevationSkin pigmentationNone or focal, low intensity (tan)Diffuse, but limited in area and old (brown)Diffuse over most of gaiter distribution (lower 1/3) or recent pigmentation (purple)Wider distribution (above lower 1/3), recent pigmentationInflammationNoneMild cellulitis, limited to marginal area around ulcerModerate cellulitis, involves most of gaiter area (lower 2/3)Severe cellulitis (lower 1/3 and above) or significant venous eczemaIndurationNoneFocal, circum-malleolar (<5 cm)Medial or lateral, less than lower 1/3 of legEntire lower 1/3 of leg or moreActive ulcers, n012>2Active ulceration durationNone<3 months>3 mo, <1yearNot healed >1 yearActive ulcer, sizeNone<2 cm diameter2-6 cm diameter>6-cm diameterCompressive therapyNot used or not compliantIntermittent use of stockingsWears elastic stockings most daysFull compliance: stockings + elevationGSV, Great saphenous vein; SSV, small saphenous vein Open table in a new tab GSV, Great saphenous vein; SSV, small saphenous vein Because patient satisfaction depends upon addressing his or her chief complaint, the specific primary reason for treatment is also important to indicate. Common symptoms of venous disease include aching, burning, itching, heaviness, swelling, cramping, and local inflammation in the affected limb, among others. A history of superficial or deep venous disease or interventions, or both, may influence both the performance and the results of EVA procedures and is therefore important to describe. Specifically, the following interventions are important: use of graduated compression stockings; a history of venous stripping and/or ligation of truncal veins, ambulatory phlebectomy, sclerotherapy, subfascial endoscopic perforator surgery (SEPS), previous EVA procedures, thrombolysis, angioplasty, or stent placement; or the presence of endovenous devices including stents, inferior vena cava filters, and central venous access devices. The presence of major comorbidities may reduce the clinical success rate or increase the rate of complications, or both. Conversely, exclusion of patient subsets due to morbidity can also bias the population and should be considered when comparing patient cohorts. The following comorbidities may influence the results of EVA and should be reported: coronary artery disease, congestive heart failure, diabetes mellitus, thrombophilias, increased body mass index, and poor overall general health.20Merchant R.F. Pichot O. Long term outcomes of endovenous radiofrequency ablation of saphenous reflux as a treatment for superficial venous insufficiency.J Vasc Surg. 2005; 42: 502-509Abstract Full Text Full Text PDF PubMed Scopus (263) Google Scholar Potential candidates for EVA include patients with reflux in an incompetent GSV or small saphenous vein (SSV) or in a major tributary branch of the GSV or SSV such as the anterior thigh circumflex vein, posterior thigh circumflex vein, or anterior accessory GSV. Therefore, the presence of reflux in these veins is important to document using duplex ultrasound imaging, as pertaining to the CEAP A5 nonsaphenous category. Use of the nomenclature recommended by the International Union of Phlebology, the International Federation of Associations of Anatomists, and the Federative International Committee on Anatomical Terminology is expected.21Caggiati A. Bergan J.J. Gloviczki P. Jantet G. Wendell-Smith C.P. Partsch H. International Interdisciplinary Consensus Committee on Venous Anatomical TerminologyNomenclature of the veins of the lower limbs: an international interdisciplinary consensus statement.J Vasc Surg. 2002; 36: 416-422Abstract Full Text PDF PubMed Scopus (265) Google Scholar, 22Caggiati A. Bergan J.J. Gloviczki P. Eklof B. Allegra C. Partsch H. International Interdisciplinary Consensus Committee on Venous Anatomical TerminologyNomenclature of the veins of the lower limb: extensions, refinements, and clinical application.J Vasc Surg. 2005; 41: 719-724Abstract Full Text Full Text PDF PubMed Scopus (170) Google Scholar Variations to standard venous anatomy, when observed on the ultrasound examination, should be reported. These include tortuosity of the target vein, duplications, atresia, the presence of anatomic venous variants, or variable termination of the SSV. The diameter of the GSV and SSV, ≤2 cm of the junction with the deep vein (common femoral or popliteal) and target vein (if not the GSV or SSV) should be measured. The patient position and site of treatment should be specified. Although a combination of a directed physical examination and duplex ultrasound imaging (CEAP level II examination) is usually sufficient to characterize the anatomic and physiologic extent of lower extremity venous disease,23Min R.J. Khilnani N.M. Golia P. Duplex ultrasound evaluation of lower extremity venous insufficiency.J Vasc Interv Radiol. 2003; 14: 1233-1241Abstract Full Text Full Text PDF PubMed Scopus (51) Google Scholar diagnosis of chronic venous disorders can also be supported by direct or indirect physiologic tests.24Porter J.M. Rutherford R.B. Clagett G.P. Cranley J.J. O'Donnell T.F. Raju S. et al.Reporting standards in venous disease.J Vasc Surg. 1988; 8: 172-181PubMed Google Scholar, 25Nicolaides A.N. Investigation of chronic venous insufficiency: a consensus statement.Circulation. 2004; 102: E126-E163Crossref Google Scholar When these tests are obtained, the results should be reported. Similarly, when a CEAP level III examination is performed using computed tomography or magnetic resonance imaging, the reason for their use should be specified, the results should be reported, and the specific criteria used for diagnosis of venous abnormalities should be indicated. Definitions of clinical signs and symptoms should comply with definitions presented in the revised CEAP classification.10Eklof B. Rutherford R.B. Bergan J.J. Carpentier P.H. Gloviczki P. Kistner R.L. et al.American Venous Forum International Ad Hoc Committee for Revision of the CEAP ClassificationRevision of the CEAP classification for chronic venous disorders: consensus statement.J Vasc Surg. 2004; 40: 1248-1252Abstract Full Text Full Text PDF PubMed Scopus (1395) Google Scholar Use of the nomenclature recommended by the International Union of Phlebology, the International Federation of Associations of Anatomists, and the Federative International Committee on Anatomical Terminology is expected.21Caggiati A. Bergan J.J. Gloviczki P. Jantet G. Wendell-Smith C.P. Partsch H. International Interdisciplinary Consensus Committee on Venous Anatomical TerminologyNomenclature of the veins of the lower limbs: an international interdisciplinary consensus statement.J Vasc Surg. 2002; 36: 416-422Abstract Full Text PDF PubMed Scopus (265) Google Scholar, 22Caggiati A. Bergan J.J. Gloviczki P. Eklof B. Allegra C. Partsch H. International Interdisciplinary Consensus Committee on Venous Anatomical TerminologyNomenclature of the veins of the lower limb: extensions, refinements, and clinical application.J Vasc Surg. 2005; 41: 719-724Abstract Full Text Full Text PDF PubMed Scopus (170) Google Scholar Specific recommendations include the terms great saphenous vein or GSV (instead of long saphenous vein, greater saphenous vein, or internal saphenous vein) and small saphenous vein or SSV (instead of short saphenous vein, lesser saphenous vein, or external saphenous vein). The ultrasound criteria used to define reflux should be indicated; in current practice, most vascular laboratories consider the presence of venous flow reversal for >0.5 to 1.0 seconds with proximal compression, Valsalva maneuver, or distal compression and release to represent pathologic reflux.23Min R.J. Khilnani N.M. Golia P. Duplex ultrasound evaluation of lower extremity venous insufficiency.J Vasc Interv Radiol. 2003; 14: 1233-1241Abstract Full Text Full Text PDF PubMed Scopus (51) Google Scholar, 26Van Bemmelen P.S. Bedford G. Beach K. Strandness D.E. Quantitative segmental evaluation of venous valvular reflux with DUS ultrasound scanning.J Vasc Surg. 1989; 10: 425-431PubMed Scopus (396) Google Scholar The aspects of pretreatment preparation that may influence EVA treatment outcomes are important to describe. This includes methods used to increase the distension of the lower extremity veins, such as pretreatment ambulation, patient positioning maneuvers, temperature adjustments to the procedure room, use of tourniquets, or pharmacologic maneuvers such as the administration of vasodilators. The method of marking and mapping the target vein(s) are also important to indicate. The method of venous entry—percutaneous, surgical cutdown, or venotomy—should be stated. Imaging guidance for venous access, administration of anesthetic injections, and monitoring of other aspects of the procedure that is provided by ultrasound guidance, fluoroscopic guidance, or a combination should be reported. The type of access system (eg, micropuncture system vs larger needle) is important to report. The precise location of the percutaneous access site(s) is important to indicate as well as the reason for selection of this point (eg, absence of reflux, potential access difficulties below a certain point, and multiple large tributaries). Tumescent anesthesia is usually administered using a dilute local anesthetic to provide local anesthesia, protect surrounding tissues (including adjacent nerves and overlying skin) from the thermal injury, and mechanically collapse the vein to decrease the distance between the catheter-based heat source and the vein walls and thereby enable nonthrombotic ablation of the vein.3Min R.J. Khilnani N. Zimmet S.E. endovenous laser treatment of saphenous vein reflux: long term results.J Vasc Interv Radiol. 2003; 14: 991-996Abstract Full Text Full Text PDF PubMed Scopus (514) Google Scholar The concentration, volume, and method of administration (ie, hand-injection or mechanical device) of local anesthetic drugs should therefore be described. The use of fluoroscopy or venography must be reported. For thermal ablation techniques, the type of energy (endovenous laser or radiofrequency) along with the manufacturer of the device should be reported. The energy level (power in watts), time of energy deployment (seconds), mode of delivery (pulsed or continuous mode), and total amount of energy emitted must be reported. If a pulsed mode is used during endovenous laser ablation, the duration and frequency of the pulse should be noted. For radiofrequency, temperature of the catheter–vein interface, size of the catheter (6F, 8F), catheter and generator model, rate of catheter pull-back in cm/min, and total treatment time should be reported. For chemical ablation techniques, the concentration, type of sclerosant (including manufacturer), and volume of the sclerosing agent must be reported. If a foam solution is used, the foaming technique should be recorded. The starting point, ending point, and total length of the ablated segment should be reported in a quantitative fashion (eg, from 1 cm below the saphenofemoral junction to 1 cm above the puncture site; total, 40 cm), and for GSV ablation in relation to groin tributaries (ie, below epigastric vein). The type and timing of postprocedure care such as compression therapy should also be reported. The class and type of compression therapy and activity restrictions should be reported. Adjunctive procedures such as sclerotherapy and stab phlebectomies are commonly used in patients undergoing EVA. Because of their influence on treatment outcomes, the use and timing of any adjunctive procedures used at the time of EVA or before the initial outcomes assessment should be described. Administration of sclerosant solution through the vascular sheath encasing the laser or radiofrequency probe should be reported. The type of sclerosant, concentration, volume, and foaming technique for foam sclerotherapy should be noted. It should also be clear whether adjunctive procedures were intended as part of the initial treatment approach. Clinical research studies on EVA may be generally categorized into two types: clinical outcome studies and technology assessment studies. These studies are designed to assess the clinical efficacy and to verify the safety of EVA procedures and are expected to quantify the impact of therapy on clinical outcomes that are meaningful to patients, such as:1relief of presenting symptoms,2frequency of skin ulcer healing and time to recurrence,3prevention of progression of chronic venous insufficiency,4improvement in quality of life, and5improvement in cosmesis, or a combination of these. EVA may succeed in achieving all, some, or none of these goals; similarly, EVA may alleviate all, some, or none of the presenting symptoms. It is therefore important for authors to define the primary clinical intent of the procedure and to adjudicate success or failure by this criterion. The primary clinical intent must be a clinical outcome of importance to patients (eg, relief of the dominant presenting symptom) rather than an anatomic/imaging outcome (eg, ultrasound-proven occlusion of the target vein). Other end points of interest may also be reported, such as the continued need for compression stockings and anti-inflammatory medications after EVA and the need for additional endovenous or surgical procedures. Because causation of clinical outcomes is generally implied as related to treatment, anatomic and imaging outcome at the same follow-up points must be reported. These studies are designed to answer specific technical questions about a new treatment modality before embarking on full-scale clinical outcomes studies. For such studies, it is acceptable to report an anatomic or imaging outcome (eg, successful ultrasound-proven ablation of the target vein) as the primary outcome, but the authors must limit their conclusions accordingly and no mention of clinical efficacy may be made unless a clinical outcome was systematically evaluated. Because the specific goals of therapy will vary among patients, investigators should report outcomes in as many of the following relevant categories as possible. A number of methods may be used to report treatment success in relieving presenting symptoms. In general, the use of validated patient-reported measures of venous symptom status is preferred over “homemade” scales or other subjective assessments. Authors may choose to use disease-specific validated scales designed to provide an assessment of venous symptoms (eg, VEINES-Sym, Aberdeen Varicose Vein Score, and the Charing Cross Venous Ulcer Score). Authors may also focus on objectively documenting improvement in one or more specific symptoms; for example, validated pain scales such as a Likert scale may be used to assess lower extremity pain, although pain and discomfort are routinely addressed in the above QOL measures. Such assessments may be supplemented by objective measures of clinical improvement that are based upon physician assessment of clinical signs (eg, measurement of leg circumferences in standardized fashion for assessment of lower extremity swelling), but determination of treatment success should not rely exclusively on physician assessments because they may or may not correlate with clinical improvement, which is meaningful to patients. Presenting symptoms and QOL may improve rapidly after EVA, but meaningful evaluation of the progression of chronic venous insufficiency needs a significantly longer time. Clinical follow-up should therefore be graded as short-term (<1 year), mid-term (1 to 3 years), or long-term (>3 years). Although the CEAP system is a useful descriptive tool, it is thought to have too many static elements to be effective in monitoring change in disease status with treatment.27Vedantham S. Grassi C.J. Ferral H. Patel N.H. Thorpe P.E. Antonacci V.P. et al.Technology Assessment Committee of the Society of Interventional RadiologyReporting standards for endovascular treatment of lower extremity deep vein thrombosis.J Vasc Interv Radiol. 2006; 17: 417-434Abstract Full Text Full Text PDF PubMed Google Scholar For this reason, a number of alternative scoring systems have been developed and partially validated for assessment of venous disease severity in patients with chronic venous insufficiency. The American Venous Forum has recommended use of the VCSS to quantify the clinical severity of venous disease (Table II). The VCSS is based on physician assessment of the presence and severity of nine common stigmata of chronic venous disease and the use of compression stockings. VCSS scores correlate well with CEAP clinical class and with the presence of abnormalities in the venous system documented with ultrasound imaging.28Rutherford R.B. Padberg F.T. Comerota A.J. Kistner R.L. Meissner M.H. Moneta G.L. Venous outcomes assessment Guidelines of the American Venous Forum.in: Gloviczki P. Yao J.S.T. Handbook of venous disorders. 2nd ed. Arnold, Great Britain2001: 497-508Google Scholar, 29Meissner M. Natiello C.M. Nicholls S.C. Performance characteristics of the Venous Clinical Severity Score.J Vasc Surg. 2002; 36: 889-895Abstract Full Text PDF PubMed Scopus (108) Google Scholar, 30Ricci M.A. Emmerich J. Callas P.W. Rosendaal F.R. Stanley A.C. Naud S. et al.Evaluating chronic venous disease with a new venous severity scoring system.J Vasc Surg. 2003; 38: 909-915Abstract Full Text Full Text PDF PubMed Scopus (48) Google Scholar For studies that focus primarily on patients with venous ulcers, there also exist measures targeted to this subgroup.15Smith J.J. Guest M. Greenhalgh R.M. Davies A.H. Measuring the quality of life in patients with venous ulcers.J Vasc Surg. 2000; 31: 642-649Abstract Full Text Full Text PDF PubMed Scopus (139) Google Scholar, 16Franks P.J. Moffatt C.J. Health related quality of life in patients with venous ulceration: use of the Nottingham health profile.Qual Life Res. 2001; 10: 693-700Crossref PubMed Scopus (89) Google Scholar It is important to assess QOL in patients with venous insufficiency because it provides valuable information on the patient-perceived burden of illness. When QOL is assessed, a generic QOL measure, such as the Medical Outcomes Study Short Form 36 (SF-36) measure, and a venous disease–specific QOL measure should be used. In recent years, a number of venous disease–specific QOL measures have been developed and at least partly validated; three are listed here:•The VEINES-QOL/Sym consists of 26 question items that measure venous symptoms, limitations in daily activities due to venous disease, psychologic impact of venous disease, and change over time. The VEINES-QOL/Sym has undergone comprehensive and rigorous psychometric evaluation and is acceptable, reliable, valid, and responsive for use as a patient-reported measure of outcome in chronic venous disease.11Rutherford R.B. Padberg Jr, F.T. Comerota A.J. Kistner R.L. Meissner M.H. Moneta G.L. Venous severity scoring: a adjunct to venous outcome assessment.J Vasc Surg. 2000; 31 (Jun): 1307-1312Abstract Full Text Full Text PDF PubMed Scopus (574) Google Scholar, 13Lamping D.L. Abenhaim L. Kurz X. Schroter S. Kahn S.R. Measuring quality of life and symptoms in chronic venous disorders of the leg: development and psychometric evaluation of the VEINES-QOL/Sym questionnaire.Qual Life Res. 1998; 7: 621-622Google Scholar, 17Wiebe S. Guyatt G. Weaver B. Matijevic S. Sidwell C. Comparative responsiveness of generic and specific quality-of-life instruments.J Clin Epidemiol. 2003; 56: 52-60Abstract Full Text Full Text PDF PubMed Scopus (362) Google Scholar•The CIVIQ-2 is a 20-question survey that has been validated for use in patients with chronic venous disease and has been used in a previous randomized trial comparing EVA with surgical therapy.18Kahn S.R. Milan C.E. Lamping D.L. Kurz X. Bérard A. Abenhaim L.A. VEINES Study GroupRelationship between clinical classification of chronic venous disease and patient-reported quality of life: results from an international cohort study.J Vasc Surg. 2004; 39: 823-828Abstract Full Text Full Text PDF PubMed Scopus (135) Google Scholar, 19Launois R. Reboul-Marty J. Henry B. Construction and validation of a quality of life questionnaire in chronic lower limb venous insufficiency (CIVIQ).Qual Life Res. 1996; 5: 539-554Crossref PubMed Scopus (342) Google Sch

Tight junctions and compression therapy in chronic venous insufficiency

Tight junctions (TJs) provide a barrier function, inhibiting solute and water flow through the paracellular space. There had been no analysis until now as to how tight junction molecules could be involved in the pathology of patients with chronic venous insufficiency. The aim of the study was to analyse the expression pattern of TJ-molecules occludin (OCLN), claudin-1 (CLDN-1), claudin-3 (CLDN-3) and claudin-5 (CLDN-5) on mRNA and protein level in patients with edema, venous leg ulcers and healthy controls. Biopsy specimens were taken in healthy individuals and in patients before, and four weeks after compression therapy. mRNA-expression was determined by using reverse-transcriptase and polymerase chain reaction (RT-PCR) and the protein-expression was determined by Western blotting from tissue specimens. Quantification performed determining the expression for TJ-molecules displayed diminished expression for CLDN-1 (p<0.01) and CLDN-5 (p<0.01) in patients with chronic venous insufficiency in comparison with healthy controls on mRNA as well as protein level. No statistical differences were detected for OCLN and CLDN-3 between the edema group and healthy controls. There was a significantly elevated expression (p<0.01) on mRNA and protein level between the leg ulcer group and healthy controls for OCLN and CLDN-3. Densitometric evaluation revealed a more significantly elevated expression (p<0.01) for CLDN-1 and CLDN-5 on mRNA and protein level after four weeks of compression therapy in comparison with prior to treatment for the edema as well as the leg ulcer group. Compression therapy tightens the paracellular barrier via elevated expression of specific TJs and prevents thereby the progression of chronic venous insufficiency due to inhibited permeability of fluid into the perivascular tissue.

Micronized Purified Flavonoid Fraction (MPFF)*: A Review of its Pharmacological Effects, Therapeutic Efficacy and Benefits in the Management of Chronic Venous Insufficiency

Initially, the progression of chronic venous insufficiency is related to venous hypertension. The earliest complaints or symptoms, as well as vessel wall deterioration, valve restructuring, and, eventually, varicose veins, result not only from elevation of pressure, but also from a cascade of biochemical events related to both the macro- and the microcirculation. Thickening and remodelling of the venous wall are influenced by two parameters: abnormal shear stress and hypoxia that activate the endothelium first at the level of valve cusps and then in large veins. Hypoxia leads to activation of the endothelium and leukocyte accumulation. By inhibiting endothelial activation, micronized purified flavonoid fraction (MPFF) (Daflon 500 mg), an edema-protective agent, can prevent the inflammatory cascade resulting from the leukocyte-endothelium interaction. This subsequently delays the appearance of reflux and inhibits the initiation of the vicious circle ending in enhanced venous pressure. This is how Daflon 500 mg relieves patients from symptoms and edema and possibly also prevents the appearance of varicose veins. Rheological disturbances also play a major role in the appearance of these disorders. Furthermore, venous hypertension provokes leakage from the vessels and capillaries exhibiting increased permeability, leading to increases in hydrostatic load, and overloading of the lymphatic network, which subsequently results fluid exudation causing edema. Microcirculatory dysfunction leads to capillary damage, skin changes and venous leg ulcers. The clinical efficacy of Daflon 500 mg in venous leg ulcers has been demonstrated by several randomised controlled studies, in which the rate of ulcer healing was significantly shortened. An explanation for the ability to speed ulcer healing comes from the protection Daflon 500 mg exerts on the microcirculation.

C-reactive protein and red cell aggregation correlate with late venous function after acute deep venous thrombosis

Risk factors leading to development and subsequent progression of chronic venous insufficiency after acute deep venous thrombosis (DVT) are only partially identified. Inflammation and rheologic abnormalities might have a causative role. The purpose of this study was to investigate C-reactive protein (CRP), D -dimer, and blood rheologic parameters in patients after acute DVT in relation to clinical outcome. Patients with a history of acute proved DVT underwent clinical examination and duplex ultrasound scanning of the veins, and Venous Clinical Severity Score (VCSS) and Venous Segmental Disease Score (VSDS) were calculated. Further, CRP, D -dimer, and several rheologic parameters were determined and related to outcome as assessed with venous scores. Forty-three patients were examined 28 (median) months after the index event. Patients had higher CRP ( P < .001), D -dimer ( P < .001), red blood cell aggregation ( P < .01), fibrinogen concentration ( P < .01), and leukocyte count ( P < .05) than did healthy control subjects. CRP and red blood cell aggregation were positively correlated with VCSS ( r = 0.42 and P < .01, and r = 0.30 and P < 0.05, respectively). Multivariate regression analysis showed that the relation between CRP and VCSS was independent of other laboratory and rheologic parameters and of age, total thrombus load, duration of compression therapy after the index event, recurrence, recanalization, and presence of comorbid conditions ( P < .05). CRP is independently related to the severity of venous dysfunction in patients after acute DVT. Chronic inflammation as well as changes in blood rheologic parameters may be causally involved in the development of chronic venous insufficiency occurring in the medium-term and long-term course after acute DVT.

Modulation of urokinase-type and tissue-type plasminogen activator occurs at an early stage of progressing stages of chronic venous insufficiency.

Chronic venous insufficiency (CVI) progresses through a series of clinical stages, from healthy skin to poorly healing leg ulcers. The aim of this study was to analyse the distribution pattern and activity level of urokinase-type (uPA) and tissue-type plasminogen activators (tPA) in normal skin and in tissue biopsies of progressing stages of CVI, prior to and including venous ulceration. Biopsies 6 mm thick were taken from 14 healthy volunteers and 37 patients with 5 different stages of CVI: telangiectases; stasis dermatitis; hyperpigmentation; lipodermatosclerosis; and leg ulcer. Changes in the enzymatic activity and spatial localization of uPA and tPA during the progression of CVI were examined using in situ histological zymography. Normal skin and skin with telangiectases showed a punctate PA activity, consisting of both uPA and tPA activity. As CVI progressed, an increase in the distribution of uPA and a decrease in tPA activity was observed. The spatial localization of uPA was widespread within the dermis of biopsies from stasis dermatitis and lipodermatosclerosis and was associated in particular with the dermoepidermal junction. Hyperpigmented skin revealed a pattern of PA expression similar to that of healthy skin. However, leg ulcer specimens exhibited peak levels of uPA with little tPA. Furthermore, a plasminogen-independent protease activity that was not present in any of the earlier stages of CVI appeared. Our results indicate that there are profound changes in PA activity during the progression of CVI and that these changes begin early in CVI, for example, in stasis dermatitis. We hypothesize that the balance or imbalance of the PA activity in the later stages of CVI is an important pathogenic factor for the development of venous leg ulcer.

Predictive Values in the Progression of Chronic Venous Insufficiency Associated with Superficial Venous Incompetence

The purpose of this study was to define predictive values in the progression of chronic venous insufficiency in patients with isolated superficial venous incompetence using duplex ultrasound and air plethysmography (APG). Five hundred eight legs in 371 patients with isolated superficial venous incompetence were included in this study. A color duplex scanner with a 5- to 10-MHz linear transducer was used to assess the distribution and the extent of venous reflux as well as the duration of reflux and the retrograde peak velocity at the saphenofemoral junction, greater saphenous vein in the thigh, and the saphenopopliteal junction. Venous reflux was considered to be present if the duration of reflux was greater than 0.5 s. The extent of greater saphenous vein is divided into 3 types. Type I: reflux from the groin to the ankle. Type II: reflux from the groin to the below-knee level. Type III: reflux from the groin to the above-knee level. Values obtained by APG were the venous volume (VV), venous filling index (VFI), ejection fraction (EF), and residual venous fraction (RVF). Between-group differences were analyzed using Wilcoxon's nonparametric rank sum test. Type I limbs had highest incidence of advanced chronic venous symptoms. Based on the duplex-derived duration of reflux and retrograde peak velocity in Type I limbs, there were three major groups: limbs with a retrograde peak velocity greater than 30 cm/s and a duration of reflux less than 3 s (group A), limbs with a retrograde peak velocity greater than 30 cm/s and a duration of reflux greater than 3 s (group B) and limbs with a retrograde peak velocity of less than 30 cm/s and a duration of reflux greater than 3 s (group C). Most of the class 2 and class 3 limbs belonged to Group C, whereas most of the class 4 limbs and all of the class 5 and class 6 limbs belonged to group A and group B. APG-derived VFI had significantly higher values in group A and group B compared with group C (P < 0.002). Peak velocity greater than 30 cm/s had a high positive predictive value of 75.0% with a sensitivity of 91.1%. Although duplex-derived duration of reflux is widely used to assess venous reflux, our data suggest that the peak velocity is a better predictor of the progression of chronic venous insufficiency and that it correlates well with the severity of the clinical manifestation in cases with isolated superficial venous insufficiency.

Predictive values in the progression of chronic venous insufficiency associated with superficial venous incompetence

Predictive values in the progression of chronic venous insufficiency associated with superficial venous incompetence