CONTENTS  •  Volume 14  Number 3 1999

Editorial

Original Articles

100   Leucocyte Rheology at Baseline and after Activation in Post-phlebitic Syndrome
G. Caimi, B. Canino, F. Ferrara, M. Montana and R. Lo Presti

105   Haemorheological Profile in Chronic Venous Insufficiency
G. Azaceta, S. Romero, C. Lorente, J. A. Moreno, T. 0ave, A. Vaquerizo, M. Azcona and M. Gutiérrez

111   Pregnancy, Oral Contraception, Hormone Replacement Therapy and the Occurrence of Varicose Veins: Edinburgh Vein Study
A. J. Lee, C. J. Evans, C. M. Hau, P. L. Allan and F. G. R. Fowkes

118   Clinical Relevance of Neovascularisation on Duplex Ultrasound in the Long-Term Follow-up After Varicose Vein Operation
M. G. De Maeseneer, I. F. Tielliu. P. E. Van Schil, S. G. De Hert and E. J. Eyskens

Short Report

Case Report

Abstracts

Letter

Philip D. Coleridge Smith

Much of my research in recent years has centred on investigating the metabolism of leucocytes in patients with chronic venous disease. I had hoped that this would have led to the development of better treatments for patients with venous ulceration but this does not yet seem to be the case. I am not alone in my pursuit of an answer to this condition, and others have also investigated the systemic inflammatory response in patients with venous ulceration. In this issue Caimi et al. and Azaceta et also have also investigated aspects of the inflammatory response. They have confirmed that there are elevated markers of inflammation in this condition as well as abnormalities of haemorheology. A series of other investigators has become interested in this question and there is a growing body of research which confirms that many inflammatory events take place in the processes leading up to leg ulceration, including stages as early as uncomplicated varicose veins. The question remains however, is this a response to something or the actual cause of skin damage and leg ulceration? It has so far proved difficult to find a definitive answer to this question. A problem faced by all researchers in this field is the absence of a satisfactory animal model which could be used to study many of the biochemical events which lead up to ulceration. It has been possible to produce venous hypertension in one or two animal models, but this has never resulted in ulceration. This leaves researchers in this field with normal human volunteers and patients to study. Clearly, this state of affairs severely limits the progress which can be made since it would be unethical to produce a venous ulcer in a normal volunteer! In my research I have looked at the early inflammatory events in volunteers and observed both leucocyte sequestration and activation of leucocytes in response to a short period (30 minutes) of venous hypertension. This to me remains convincing evidence that venous hypertension exerts its effects through the inflammatory events. It is also clear that some patients are much more susceptible to the effects of venous hypertension than others. Most phlebologists know of patients with severe, longstanding venous hypertension who have normal skin and of patients with much lesser degrees of venous disease who suffer severe venous ulceration.

Understanding the basis of this difference is crucial to knowing the causes of venous ulceration. It is clear that in those patients who suffer skin changes preceding leg ulceration the extent of inflammatory activation is greater than in those patients who do not suffer skin changes, and there is little correlation between markers of inflammation and indices of venous function. Unfortunately it is not possible to follow normal volunteers or patients with currently uncomplicated venous disease to see if any of the inflammatory mediators predicts the development of skin changes in the long term. Such a study could last many years! At the same time we have to explain why compression treatment is so effective at healing of venous ulcers. I have not been convinced by suggestions that compression achieves its success by restoring incompetent valves or improving large vein physiology. It has been shown that skin microcirculatory flow velocities accelerate at relatively low levels of compression (20-40 mm Hg). Acceleration of flow would decrease the tendency for leucocyte adhesion, and it has been shown that leucocyte sequestration in the lower limb during venous hypertension is prevented by application of class 3 medical compression stockings. These data suggest to me that somewhere in the leucocyte interaction with endothelium in the skin capillaries we shall find an explanation for the factors leading to leg ulceration. I believe that it is far better to understand this part of the process than to look at more advanced stages of the disease process when ulceration has already developed. Unfortunately neither my own research nor that of others has shown exactly where this abnormality of Function lies. Many complex processes of leucocytes and endothelial cells are involved in interaction of these cells in the microcirculation. In addition, the defect may lie in further mechanisms which protect us from the initiation of inflammation during venous hypertension. Resolving these questions may take an approach from several directions. As well as comparing measurements from healthy volunteers with those in patients with venous disease it will probably be necessary to investigate the genetic markers for venous ulceration. Although factor V Leiden gene defect has been shown to be associated with venous ulceration this probably arises from its tendency to cause venous thrombosis. There must be further genes which confer sensitivity or resistance to leg ulceration. Such a study will necessarily be of considerable complexity. but without it elucidating the causes of leg ulceration will remain difficult. Clearly much remains to be discovered concerning the causes of venous leg ulceration, but without enthusiastic researchers such as Caimi, Azaceta and others we may never find the answer!

Contents

P. J. Franks¹, C. J. Moffatt¹. D. A. Ellison², M. Connolly¹. S. Fielden³, L. Groarke² and C. N. McCollum^2
1Centre for Research & Implementation of Clinical Practices Thames Valley University, London; ²Department of Surgery, University Hospital of South Manchester. Manchester: and ³Riverside Community Health Care Trust, Parsons Green Health Centre, London, UK

Objective: To evaluate health-related quality of life (HRQ0L) in a prospective randomised trial of patients suffering from venous ulceration, comparing the original four-layer bandage system with a new four-layer system (Profore).

Design: Randomised prospective parallel groups trial.

Results: In all, 231 of 232 patients who entered the trial completed the initial questionnaire, with 208 patients completing at least one follow-up questionnaire. Improvements were noted for all scores after 24 weeks, which were significantly greater in the 167 patients whose ulcers had healed compared with the 41 whose ulcers remained unhealed for the domains of Sleep (mean difference [d] = 10.5, 95% CI 2.9 to 18.1, p=0.007) and Bodily Pain (d= 8.9, 95% CI 1.3 to 16.5, p=0.023), with a large difference for Physical Mobility (d = 5.0) which failed to achieve statistical significance (95% CI —0.5 to 10.6, p = 0.07) following adjustment for the baseline scores. There were similar mean scores between the 99 patients treated with the original bandage system and 109 treated with Profore for all domains of the NHP, the largest adjusted difference favouring Profore for Energy (d = 3.7, 95% CI —3.8 to 11.2, p = 0.34).

Keywords: Compression treatment; Four-layer bandage; Quality of life: Venous ulceration

Correspondence and offprint requests to: Dr. P. J. Franks, Centre for Research & Implementation of Clinical Practice, Thames Valley University. Wolfson Institute of Health Sciences, 32—38 Uxbridge Road, London W5 2BS, UK.

Contents

G. Caimi¹. B. Canino¹, F. Ferrara², M. Montana¹ and R. Lo Presti^1
1Istituto di Clinica Medica e Malattie Cardiovascolari, and ²Divisione di Angiologia, Università di Palermo, Palermo, Italy

Methods: In 22 subjects with PPS we determined leucocyte filtration [unfractionated, mononuclear (MN) and PMN cells], employing the St George Filtrometer, PMN membrane fluidity using the fluorescent probe 1-[4-(trimethylamino)phenyl]-6-phenyl-1,3,5-hexatriene (TMA-DPH) and PMN cytosolic Ca²⁺ concentration using the fluorescent probe Fura 2-AM. Subsequently we determined the same PMN parameters after in vitro activation with 4-phorbol I 2-myristate 13-acetate (PMA) and N-formyl-methionyl-leucyl-phenylalanine (fMLP).

Results: At baseline we observed a difference in the filtration parameters of unfractionated and MN cells and an increase in PMN cytosolic Ca²⁺ concentration. After activation, a significant variation in PMN filtration parameters was evident both in normals and in PPS subjects, although in subjects with PPS this variation, especially with PMA, was significantly greater. We found a decrease in PMN membrane fluidity and an increase in PMN cytosolic Ca²⁺ concentration only in subjects with PPS.

Conclusion: These results suggest that there is a functional alteration of systemic leucocytes in PPS, in which the mechanisms are not yet clear.

Keywords: Leucocyte filtration; Neutrophil activation; Neutrophil cytosolic Ca²⁺: Neutrophil membrane fluidity; Post-phlebitic syndrome

Correspondence and offprint requests to: Prof. G. Caimi. Via Leonardo da Vinci. 52, 1-90145 Palermo, Italy.

Contents

G. Azaceta¹, S. Romero¹. C. Lorente². J. A. Moreno¹, 1. Olave¹, A. Vaquerizo³, M. Azcona² and M. Gutiérrez¹
Departments of ¹Haematology. ²Angiology and Vascular Surgery, and ³Anaesthesiology. Hospital Clinico Universitario de Zaragoza, Spain

Background: In recent years, pathophysiological studies and treatment approaches of chronic venous insufficiency (CVI) have focused on haemorheology.

Objective: To analyse erythrocyte aggregation (EA) and blood viscosity (BV) in mild and severe stages of CVI.

Methods: In 147 patients (three severity stages), EA was measured with a photometric aggregometer, and BV with a cone-plate viscosimeter. Patients with concomitant pathologies affecting haemorheology were excluded.

Results: EA was higher in patients (mean EA 10M: 16.4 vs 14.5 control), increasing progressively with the evolution of CVI (p <0.001). Greatest differences were found for stage III (mean EA 1OM: 17.6) vs stage II (15.7) and stage 0 (14.5) respectively (p<0.001), but rheological abnormalities exist in early grades (1: 16.7) (p<.01). Fibrinogen and age had a strong influence on EA (p <0.003 and p <0.001 respectively). When a covariance analysis avoided their effect, significant global differences between CVI groups persisted. BV at high shear rate was increased at advanced stages (III: mean 3.3 centipoise (cp); 1: 3.1 cp) (p<.05).

Conclusions: We found progressive impairment of the haemorheological profile with the worsening stages of CVI, related to age, severity stage and fibrinogen. Rheological impairment is likely to play a part in the pathophysiology of CVI, and perhaps may be useful in its management.

Keywords: Blood flow: Blood viscosity; Erythrocyte aggregation; Haemorheology; Shear rate; Venous insufficiency: Venous thrombosis

Correspondence and offprint requests to: Dra Gemma Azaceta, Servico de Hematologia, Hospital Clinico Universitario de Zaragoza, Avda San Juan Bosco 15. E-50009 Zaragoza, Spain.

Tel: +34 76 556400. Fax: +34 76 5659952.

Contents

A. J. Lee¹, C. J. Evans¹, C. M. Hau¹, P. L. Allan² and F. G. R. Fowkes^1
1Wolfson Unit for Prevention of Peripheral Vascular Diseases, Public Health Sciences, University of Edinburgh, Edinburgh, UK; and ²Clinical Imaging, Royal infirmary of Edinburgh, Edinburgh, UK

Objective: To determine the relationship between varicose veins and duration of menstrual life, age of menopause, pregnancy, oral contraceptive use and hormone replacement therapy (HRT).

Design: Cross-sectional study.

Setting: City of Edinburgh, UK.

Participants: Eight hundred and sixty-seven women aged 18—64 years randomly selected from 12 general practices.

Methods: After completing a questionnaire, which included questions on reproductive history, the women underwent a comprehensive clinical examination including the assessment of varicose veins (trunk, hyphenweb and reticular varices), followed by duplex scanning of their legs.

Results: Women who had been pregnant at least once were more likely to have minor hyphenweb or reticular varices than women who had never been pregnant (p ≤ 0.10). Women aged 35—54 years who were current users or ex-users of the oral contraceptive pill had a lower prevalence of trunk varicose veins than women who had never taken the pill (p ~ 0.10). HRT was also associated with a lower prevalence of trunk varices (p ≤ 0.05).

Conclusions: These results suggest that alterations in the balance of the sex hormones may have a role in the aetiology of varicose veins.

Keywords: Epidemiology; Hormonal factors; Pregnancy; Varicose veins

Correspondence and offprint requests to: Dr Amanda Lee. Wolfson Unit for Prevention of Peripheral Vascular Diseases, Public Health Sciences, University of Edinburgh, Teviot Place, Edinburgh EH8 9AG, UK.

Tel: +44 (0)131 650 3249. Fax: +44 (0)131 650 6904. E-mail: Amanda.Lee@ed.ac.uk

Contents

M. G. De Maeseneer¹. I. F. Tielliu¹, P. E. Van Schil¹, S. G. De Hert² and E. J. Eyskens^1
1Department of Surgery, Division of Vascular Surgery and ²Department of Anesthesiology, University Hospital, Antwerp, Belgium

Objective: To evaluate the clinical relevance of neovascularisation at the saphenous ligation site.

Design: Long-term follow-up after previous varicose vein surgery in a single patient group.

Setting: Vascular clinic of a university hospital.

Patients: Eighty-two patients (106 limbs) with a mean follow-up period of 56 months after correct saphenous ligation were submitted to duplex scanning.

Intervention: Clinical assessment and colour duplex scanning of all the operated limbs. Reintervention in 15 limbs with perioperative evaluation of recurrent veins.

Main outcome measures: Limbs with and without recurrent varicose veins wet-c classified according to the degree of neovascutarisation: grade 0 = no new communicating veins, grade 1 = tiny new vein with diameter <4 mm, grade 2 = new communicating vein with diameter >4 mm and pathological reflux. On reintervention the presence of neovascular veins at the site of the previous ligation was checked.

Results: In 68 limbs without recurrent varicose veins, grade 0 was observed in 50 limbs (74%). grade 1 in 12 limbs (18%) and grade 2 in six limbs (9%). In 38 limbs with recurrent varicose veins, grade 0 was diagnosed in eight limbs (21 %), grade 1 in four limbs (11%) and grade 2 in 26 limbs (68%). In 15 limbs with recurrent varicose veins and grade 2 neovascularisation, reintervention confirmed the duplex findings.

Conclusions: The presence of grade 2 neovascularisation was associated with the recurrence of varicose veins, suggesting a causal relationship.

Keywords: Duplex ultrasound; Long-term follow-up; Neovascularisation; Reoperation; Saphenous vein surgery: Varicose vein recurrence

Correspondence and offprint requests to: M. 0. De Maeseneer. Department of Surgery, Division of Vascular Surgery. University Hospital Antwerp, Wilrijkstraat 10, B-2650 Edegem, Belgium.

Tel: (32) 3 821 33 30: Fax: (32) 3 825 13 08.

Contents

A. Zelikovski, A. Koren, E. Stelman, A. Avrahami, J. Cohen and M. Haddad
Vascular Surgery Unit, Rabin Medical Center (Beilinson Campus), Petah Tiqva, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv. Israel

Objective: To demonstrate the effect of a newly developed device, the Muscle Pump Activator, on venous flow velocity of the lower limbs.

Design: Prospective study.

Setting: Tertiary-care teaching hospital.

Subjects: A group of 30 healthy volunteers.

Interventions: The Muscle Pump Activator is a self-activated pedal device for use in the sitting position. Venous flow velocity was measured by duplex examination of the femoral vein at rest and during activation by the subject of the device. Subjective reports were also collected.

Results: Venous flow velocity increased from 13.3 (SD 2.4) cm/s at rest to a maximum of 70.3 (SD 14.4) cm/s during 15 s of pedalling (p<0.01). This represents an increase in flow of 439 (SD 12.4)%. Ease of use and comfort of the device were reported by all the volunteers.

Conclusions: This Muscle Pump Activator significantly improves venous flow velocity and holds promise as a useful adjunctive modality for the prevention of postoperative deep vein thrombosis. It is easy to use and well tolerated. Studies are now needed in clinical settings with large groups of patients.

Keywords: Deep vein thrombosis; Muscle pump; Prevention

Correspondence and offprint requests to: A. Zelikovski. MD, Vascular Surgery Unit, Rabin Medical Center (Beilinson Campus), Petah Tiqva 49100, Israel.

Tel: 972-3-9376666; Fax: 972-3-937-6678.

*patent pending. Manufactured by Mego-Afek, Israel.

Contents

M. S. Simms¹ and M. H. Simms^2
1Department of Urology, City Hospital, Nottingham and ²Department of Vascular Surgery, Selly Oak Hospital, Selly Oak, Birmingham, UK

Design: Case report.

Setting: BMI Priory Hospital, Birmingham. UK.

Patient: A 67-year-old man presenting with unilateral lower limb oedema. Past history included ipsilateral lower limb melanoma and Parkinson’s disease, treated by pergolide.

Intervention: Laparotomy to confirm a diagnosis of retroperitoneal fibrosis (RPF) causing iliac vein obstruction.

Conclusion: RPF is a rare complication of pergolide therapy for Parkinson’s disease. Previous reports have also described iliocaval obstruction and there may be an association between pergolide-induced RPF and venous complications.

Keywords: Parkinson’s disease; Pergolide; Retroperitoneal fibrosis; Venous obstruction

Contents

Copyright © 2000 Philip Coleridge Smith