Increased mast cell infiltration in familial varicose veins: pathogenetic implications?

AIM: Increased infiltration of activated mast cells has been recently implicated in the pathophysiology of varicose veins. The aim of the present study was to investigate a possible association between mast cell infiltration of primary varicose veins and clinical features, which could clarify further varicose vein pathophysiology. METHODS: Seventeen patients, operated on for primary varicose veins and greater saphenous vein incompetence, participated in the study. Mast cells, distributed within the adventitia of grossly abnormal segments of the greater saphenous vein and calf varicosities removed during surgery, were identified and measured in stained tissue sections. The mast cell count, expressed as mast cells per 10 high-power fields, was subsequently associated with clinical features, including age, gender, body mass index, familial varicose veins, duration of varicose vein disease and relation to previous pregnancies, leg symptoms and findings on physical examination, clinical class and score of chronic venous insufficiency (CEAP classification). RESULTS: Patients with family history of varicose veins (n=7) had a significantly increased mast cell infiltration (median, interquartile range) of the abnormal venous segments (16, 8.4) in comparison with those (n=10) without such a history (9.2, 7.3), p=0.005. Mast cell infiltration had a significant inverse association with age (r= -0.49, p=0.046), but not with the remaining clinical features. CONCLUSION: Our findings support the hypothesis that the increased mast cell infiltration in varicose veins is not a consequence of venous hypertension. Furthermore, the increased mast cell infiltration in familial varicose veins implies a rather primary role and therefore the presence of a distinct pathophysiology. Further investigation testing the activity of mast cells in cases of family history might reveal another step in the pathogenic mechanism of varicose veins, leading to a more rational treatment.     

Prevalence of venous insufficiency in French adults of the SUVIMAX cohort. SUpplémentation en VItamines et Minéraux AntioXydants.

BACKGROUND: The symptoms of venous insufficiency of the lower limbs (VILL) include a feeling of heaviness in the legs, pain, and nocturnal cramps, which may be combined with organic disorders (varicose veins). The objective of this study was to determine the prevalence of VILL in terms of both varicose veins and functional symptoms in the participants of the SUVIMAX cohort, which is representative of the French population for the age range under consideration (women: 35-60; men: 45-60). METHODS: Information on the venous status of 3065 subjects in the SUVIMAX cohort were collected from three different sources: yearly systematic clinical examination (1994-1996), monthly follow-up by a telematic network (1994-1998) and non-specific questionnaire (1997). Two mutually exclusive populations were thus defined on medically diagnosed varicose veins and venous insufficiency and reported varicose veins and venous insufficiency. RESULTS: Venous insufficiency was medically diagnosed in 192 men (14.6%) and 584 women (33.6%), and varicose veins were diagnosed in 143 men (74.5%) and 317 women (54.2%) from this group. Prevalence reported symptoms of venous insufficiency and of varicose veins was 13.6% and 7.4% respectively in men and 28.2% and 12.4% in women. Sex, age, body mass index and number of pregnancies were found to be correlated with the risk of venous insufficiency. CONCLUSIONS: VILL is a very common disease in French adults both as varicose veins and as functional symptoms. Venotonics were the main type of treatment but not enough use is made of elastic compression stockings.     

External banding valvuloplasty of the superficial femoral vein in the treatment of recurrent varicose veins.

OBJECTIVES: The aim of this study is to evaluate the efficacy of reconstructive surgery of primary deep venous insufficiency in preventing recurrent varicose veins. DESIGN: Retrospective analysis of patients affected by recurrent varicose veins submitted to external banding valvuloplasty of the superficial femoral vein. SETTING: A division of vascular surgery in a hospital/scientific institute. MATERIALS: Nineteen limbs (19 patients) with recurrent varicose veins, severe chronic venous insufficiency and 3rd or 4th grade reflux in the superficial femoral vein and competence of the profunda femoris vein were selected for surgical reconstructive treatment after a complete diagnostic study by continuous wave Doppler duplex scanning and descending phlebography. INTERVENTIONS: External banding valvuloplasty of the superficial femoral vein was performed in all cases: A Dacron sleeve was used in nine patients and Venocuff in 10. RESULTS: In one case a deep venous thrombosis of the calf occurred in the first postoperative period; in three cases the correction of the deep reflux was incomplete and a recurrence of the varices was observed. After a mean follow-up of 50 months, abolition of reflux and relief of symptomatology were obtained in 15 cases (78%). CONCLUSIONS: Primary deep venous insufficiency, unknown at the time of the initial operation, may be the cause of recurrent varicose veins. External banding valvuloplasty of the superficial femoral vein may abolish the reflux and correct venous hypertension, preventing recurrences.     

Hemorheology of venous insufficiency

The aim of this paper is to study the rheological properties of blood in patients with venous insufficiency. MATERIAL AND METHODS: Measurements have been performed for 20 healthy control subjects and 20 patients presenting a venous insufficiency with varicose veins of lower limbs. Blood has been withdrawn from the veins of the lower limbs at rest and after 10 minutes of venous stasis (standing position and 100 mmHg tourniquet). The following measurements have been performed: hematocrit by microcentrifugation; fibrinogen by nephelometry; plasma viscosity by means of capillary viscosimeter (Myrenne KSPV4); deformability by Hanss hemorheometer using nucleopore membranes and red blood cell aggregation and disaggregation by means of a SEFAM erythro-aggregometer. RESULTS: 1. Hematocrit was not significantly different between both groups of subjects at rest. However, it increased significantly after venous stasis in patients with varicose veins but it was not found to be increased in healthy subjects. 2. Before and after stasis, the fibrinogen level was higher in patients than in controls. After stasis, a significant increased was found only in the patient group. 3. Plasma viscosity was found to be modified as the same manner as the fibrinogen level. Besides, the fibrinogen level and plasma viscosity were found to be correlated to each other. 4. Before and after stasis, red cells of patients were significantly less deformable than those of controls. After stasis, they were found to be more altered, in patients. But there were no difference in controls before and after stasis. 5. Aggregation and disaggregation parameters have been found to be disturbed in patient group. Disturbances were more pronounced after stasis. CONCLUSION: Venous insufficiency can be characterized by alteration of rheological parameters and the blood stasis in varicose veins may enhance these alterations. These results indicate the importance of hemorheological disturbances in the pathogenesis of this disease.     

Photoplethysmography in chronic venous insufficiency

Venous photoplethysmography (P.P.G.) is a non-invasive diagnostic technique using reflection of infrared light on the skin. The record gives a curve analogous to venous pressure. Normally the venous pressure of the leg decreases in response to calf muscle exercise. We have affixed the P.P.G. transducer to the skin above the medial malleolus and have analyzed the recovery half time (T 1/2) on 170 limbs: 49 normal, 82 with superficial venous insufficiency and 39 with deep venous insufficiency. Reference tests were ascending and retrograde phlebography and venous Doppler evaluation. A tourniquet was used to occlude the superficial venous network. T 1/2 without tourniquet is useful to screen limbs with venous insufficiency. T 1/2 with tourniquet differentiates deep and superficial venous insufficiency. P.P. G. can document the rise of deep venous insufficiency in patients with varicose veins and or repermeation of deep veins or post phlebitic syndrome among patients who have had thrombophlebitis.     

Lysosomal enzymes and superoxide production in polymorphonuclear leukocytes of patients with primary varicose veins.

In order to clarify the role of reactive oxygen species and lysosomal enzymes in the etiopathogenesis of varicose veins, the investigation of their activities in serum and peripheral neutrophils of 17 patients with primary varicose veins was done. The mean activities of acid phosphatase, beta-D-glucuronidase (BDG) and N-acetyl-beta-D-glucosaminidase were higher in serum of patients with varicose veins than in serum of normal subjects. However, the mean BDG activity was lower in the patients' neutrophils and the activities of elastase and myeloperoxidase were higher than in clinically healthy persons. No changes have been observed in the lysozyme activity. The neutrophils of patients with varicose veins had a greater ability to increase superoxide production after their stimulation with opsonized zymosan or phorbol myristate acetate than the neutrophils of normal subjects, while no differences were found in the total reduction of iodonitrotetrazolium (INT) incubated with these leukocytes. The results may represent another piece of evidence suggesting the activation and involvement of neutrophils in pathogenesis of chronic venous insufficiency of lower limbs.     

Varicose veins. Chronic venous insufficiency. Lower limbs venous ulcers. Point of view

PURPOSE: Lower limbs chronic venous disorders are still considered as a minor disease from a university hospital point of view, yet it is a very common problem, affecting the quality of life, generating disability, and expensive for healthcare resources. Its teaching is neither satisfactory nor easy to do. KEY POINTS: Apart from the fact that it rarely causes death, the complexity of venous anatomy and physiopathology, the lack of animal model, common practices lumping together visible varicose veins and chronic venous insufficiency, and moreover a certain carelessness in the vocabulary probably largely explain these difficulties. Our purpose is to discuss chronic venous disorders (varicose veins, chronic venous insufficiency, venous ulcers) on the basis of semantic, of anatomical, haemodynamic and clinical forms and finally of nosology.     

Varikose: Schönheitsfehler oder Erkrankung?

According to one's subjective appraisal varicose veins will be perceived as more or less disfiguring. About 60% of the population suffer from only minor variants of varicose veins which bear no risk to health. A certain percentage will develop progressive disease with the venous ulcer representing the worst variant of chronic venous insufficiency. As long as there is no progressive disease, therapeutic modalities also account for a superior cosmetic appearance. Endoluminal procedures in particular meet with the claim for a superior treatment result with respect to cosmetic outcome without diminution of efficiency. In case of progressive venous insufficiency appearance is of inferior importance. About 70% of venous ulcers are due to primary varicose veins. Surgery of all accessible superficial refluxing veins is important to prevent recurrence. Compression treatment is highly effective in preventing chronic venous insufficiency and in venous ulcer treatment. About 60% of venous ulcers heal within a 24-week treatment period.     

Technical procedure of two-port system subfascial endoscopic perforator vein surgery (TPS-SEPS)

It has long been noted that incompetent perforating veins contribute to the development of chronic venous insufficiency and recurrent varicose veins that are complicated by skin ulcerations or liposcleroderma. For these conditions, severing of incompetent perforating veins is an effective surgical treatment. However, severing of incompetent perforating veins by a direct approach has become less commonly performed because of the excessive invasiveness of the procedure itself. We referred to 37 cases (44 legs) of varicose veins with or without active venous dermatitis, who underwent the two-port system subfascial endoscopic perforator surgery, which we devised (hereafter referred to as TPS-SEPS). According to this method, incompetent perforating veins can be severed without surgical intervention in the lesion. The criteria for insufficiency of the perforating veins (IPVs) are reverse flow demonstrated on a color-flow duplex and a caliber more than 3 mm in diameter. One hundred forty one out of one hundred fifty two IPVs were processed. A mean of 3.21 perforating veins per patient was severed using ultrasonic coagulation-incision apparatus. From these 37 cases we conclude that TPS-SEPS provides a useful tool for the surgeon interested in treating severe chronic venous insufficiency same as the single-port technique. Our TPS-SEPS is a relatively simple operation, but its skill is dependable and provides lower invasiveness than other operation procedure. From now on, it is necessary to unify the authorized name of the endoscopic surgery of perforating veins and is also important to define the indication of this method for the primary varicose veins without stasisdermatitis.     

Chronic venous insufficiency in primary varicose veins evaluated by plethysmographic technique

Venous hemodynamics were evaluated by plethysmography in normal subjects and patients with venous disorders of the lower extremity, to clarify the pathophysiology of chronic venous insufficiency (CVI) due to primary varicose veins. Expelled volume during five active dorsiflexions of the feet and venous recovery time were calculated to evaluate muscle pump efficiency and valvular competence. Limbs with CVI due to primary varicose veins showed a higher expelled volume and a more shortened refilling time than limbs with simple varicosities. With application of tourniquets, the refilling time normalized in limbs with CVI, as well as in limbs with simple varicosities. These results indicate that a high degree of venous congestion in the distal part of the calf and valvular incompetence of the superficial vein system might cause CVI due to primary varicose veins.     

Relationship between air-plethysmographic venous function and clinical severity in primary varicose veins.

AIM: The role of air plethysmography (APG) in the diagnosis of chronic venous insufficiency has not been well established. The purpose of this study was to elucidate the relationship between APG parameters and clinical severity in patients with chronic venous insufficiency. METHODS: Two hundred and ninety-four limbs in 154 patients with primary varicose veins were evaluated by APG. Limbs were categorized according to the clinical classification of chronic venous disease suggested by the Ad Hoc Committee on Reporting Standards in Venous Disease of the North American Chapter of the Society for Vascular Surgery and International Society for Cardiovascular Surgery (SVS/ ISCVS). RESULTS: The venous filling index (VFI) was significantly higher in classes 2, 3, 4, and 5+6 than in class 0 or 1, and did not differ among classes 2, 3, 4, 5+6. The ejection fraction did not differ significantly among the 6 classes, and the residual volume fraction was significantly higher in classes 2, 3, 5+6 than in class 0. CONCLUSIONS: APG is a reasonable method for distinguishing the presence or absence of chronic venous insufficiency, but it cannot discriminate the clinical severity. Among APG parameters, the VFI is the most useful diagnostic parameter in the evaluation of chronic venous insufficiency.     

Clinical features of venous insufficiency and the risk of venous thrombosis in older people

Venous thrombosis is common in older age, with an incidence of 0·5–1% per year in those aged >70 years. Stasis of blood flow is an important contributor to the development of thrombosis and may be due to venous insufficiency in the legs. The risk of thrombosis associated with clinical features of venous insufficiency, i.e., varicose veins, leg ulcers and leg oedema, obtained with a standardized interview was assessed in the Age and Thrombosis Acquired and Genetic risk factors in the Elderly (AT‐AGE) study. The AT‐AGE study is a case–control study in individuals aged 70 years and older (401 cases with a first‐time venous thrombosis and 431 control subjects). We calculated odds ratios (ORs) and corresponding 95% confidence intervals (CI) adjusted for age, sex and study centre. Varicose veins and leg ulcer were associated with a 1·6‐fold (95% CI 1·2–2·3) and 3·3‐fold increased risk of thrombosis (95% CI 1·6–6·7), respectively, while the risk was increased 3·0‐fold (95% CI 2·1–4·5) in the presence of leg oedema. The risk of thrombosis was highest when all three risk factors occurred simultaneously (OR: 10·5; 95% CI 1·3–86·1). In conclusion, clinical features of venous insufficiency, i.e., varicose veins, leg ulcers and leg oedema, are risk factors for venous thrombosis in older people.     

Study of venous insufficiency in the light of ambulatory phlebectomy

Considering an ambulatory phlebectomy is, first, a thorough analysis of the venous insufficiency: visual and manual analysis, provides macroscopic informations on the varicose veins disease; superficial venous Doppler is irreplaceable to monitor the reflux and screen varicose tracts and insufficient perforators, without clinical manifestations, as well as recurrent sources if neglected; ultra-sonography and varicose veins phlebography will enlighten borderline cases; the evaluation of the results of previous treatments on the tissues (surgery, sclerosis, thrombectomy), of trophic complications (sclerous hypodermatitis, calcinosis) and of scarred or pigmented abnormalities, will permit to "evaluate the area" of this ambulatory phlebectomy.     

What is the medical rationale for the treatment of varicose veins?

Varicose veins occur in up to one-third of Western populations and are associated with clinical manifestations ranging from asymptomatic, isolated varicose veins (C2 disease) to venous ulceration. While the development of less invasive treatment options, such as endovenous ablation and sclerotherapy, have been well accepted by patients they have led to increased utilization of scarce health-care resources. While few would argue with the treatment of acute complications such as superficial venous thrombosis and variceal haemorrhage, the role of interventional treatment in the management of lifestyle limiting symptoms and the prevention of disease progression may be debatable. Good-quality evidence does suggest that surgical management of varicose veins is associated with improved quality of life at costs below the thresholds of many Western health-care systems. However, the progression of isolated C2 disease to advanced chronic venous insufficiency occurs infrequently and the role of treatment to prevent such progression remains undefined at present.     

Impaired ambulatory venous function in lymphedema assessed by near-infrared spectroscopy.

AIM: The aim of this study was to investigate venous function in patients with leg lymphedema during exercise using near-infrared spectroscopy (NIRS), compared with that of patients with chronic venous insufficiency (CVI). METHODS: Forty-three legs of 33 patients (5 males, 28 females; mean age: 53 years) with leg lymphedema without varicose veins or deep vein thrombosis underwent a treadmill walking test with simultaneous NIRS. For comparison, 136 legs of 91 patients (35 males, 56 females; mean age: 56 years) with varicose veins as a CVI group and 45 legs of 38 healthy volunteers (23 males, 15 females; mean age: 50 years) were also evaluated in the same method. Deoxygenated hemoglobin (HHb) was continuously measured during exercise, and the ambulatory venous retention index (AVRI) of each leg was obtained from the serial changes in HHb. RESULTS: The mean AVRI of the lymphedema group was significantly higher than that of healthy legs and significantly lower than of legs with moderate or severe CVI. Furthermore, it was similar to that in the mild CVI group. CONCLUSIONS: Venous function is impaired in exercising legs with lymphedema, and corresponds to that in legs with mild venous insufficiency. The treatment of lymphedema should take CVI into consideration.     

Circulating leucocyte adhesion molecules in chronic venous insufficiency.

BACKGROUND: Enzyme-linked immunosorbent assay (ELISA) techniques have detected the existence of circulating forms of intercellular adhesion molecule-1 (ICAM-1), vascular endothelial adhesion molecule-1 (VCAM-1) and E-selectin, all of which mediate leucocyte-endothelial adhesion. This study determined whether circulating cell adhesion molecules were increased in patients with chronic venous insufficiency (CVI) which causes venous stasis. PATIENTS AND METHODS: Before and after walking and upon recovery blood samples were drawn from the saphenous vein in 20 CVI patients: 10 with varicose veins (group 1), 10 with deep venous insufficiency (group 2). 10 healthy controls were enrolled. The total leucocyte count and the soluble levels of ICAM-1, VCAM-1 and E-selectin were determined. RESULTS: After walking, the total leucocyte count decreased significantly (p < 0.01) only in group 2 and sICAM-1 and sVCAM-1 increased significantly (p < 0.01). Upon recovery, these significant differences remained in group 2. No significant modification was observed at any stage of the study in group 1 or in the control group. CONCLUSIONS: These results suggest persistently high levels of circulating adhesion molecules may contribute to worsen microvascular perfusion, which leads to the onset of trophic damage in CVI.     

The incidence and cardiovascular risk indicators of deep venous thrombosis.

BACKGROUND: To estimate the incidence and associated risk indicators of deep venous thrombosis (DVT) in the lower extremities. PATIENTS AND METHODS: A population-based 5-year follow-up study with self-administered questionnaire. The study included 5568 persons at the beginning, with a follow-up of 17,005 person-years. A questionnaire was sent to all residents in the city of Tampere, Finland, born in 1929, 1939 and 1949. In the first survey the number of participants was 5568 and in the second questionnaire 4903. The participation rates were 83% and 88%. RESULTS: The incidence of DVT was 140 per 100,000 person-years. The life-time prevalence of DVT was 3.1%. In a univariate analysis, the appearance of a new DVT during the follow-up time (incidence) was statistically significantly associated with pre-existing varicose veins, sex-steroid therapy, heart failure and arterial insufficiency in the lower limbs. In multivariate analysis varicose veins, arterial insufficiency in the lower limbs and sex-steroid therapy remained as significant risk factors associated with DVT. CONCLUSIONS: The study confirms that the incidence of DVT in Finland is close to the estimates in other Western populations. Pre-existing varicose veins, sex-steroid therapy and arterial insufficiency in the lower limbs are independent risk factors for DVT in our population-based study.     

Three treatments for chronic venous insufficiency: escin, hydroxyethylrutoside, and Daflon

Escin, hydroxyethylrutoside (HR), and Daflon have been shown to be safe and effective for the treatment of chronic venous insufficiency (CVI). They seem to work differently than compression therapy, suggesting that they would usefully augment this therapy. All three phlebotonics attenuate the drop in adenosine triphosphate in venous endothelial cells during hypoxia. This attenuates (1) the inflammation response, (2) the attraction of neutrophils, (3) damage to the veins, and (4) the release of growth factors. These factors otherwise would perpetuate venous insufficiency and contribute to varicose veins. Additional independent effects that would be useful for the treatment of CVI are that they reduce permeability and fragility; HR, Daflon, and perhaps escin increase venous tone; escin inhibits hyaluronidase; Daflon and probably HR are attracted to the veins. With regard to similarity, no differences in effect have been established among these phlebotonics.