Prevention of venous thromboembolism in patients undergoing surgical treatment of varicose veins

Abstract

Introduction:

There is no consensus among surgeons with regard to prevention of venous thromboembolism (VTE) in patients undergoing surgical treatment of varicose veins. We performed a systematic review of the available literature.

Methods:

We systematically searched the online database from PubMed for studies about the incidence of VTE and thromboprophylaxis in varicose vein surgery. We included 13 papers for review.

Results:

The incidence of VTE after varicose vein surgery remains unclear. Most retrospective case series report an incidence of deep venous thrombosis (DVT) of approximately 1%, based on a clinical diagnosis. However, three prospective studies have systematically detected DVT by means of duplex ultrasound and showed that the true incidence might be 5–10 times higher than expected on a clinical basis.

Discussion:

More data on the incidence of VTE, and the need for postoperative thromboprophylaxis are necessary to formulate evidence-based clinical guidelines. Therefore, high-quality randomised clinical trials, with high numbers of included patients, and ideally comparing prophylaxis to placebo are warranted.

Keywords

varicose veins venous thromboembolism thrombosis prophylaxis

Introduction

Varicose veins are very common. These are veins that are swollen and have a tortuous course. Patients can regard it as a cosmetic problem and also complain about pain and itching, a feeling of heaviness in the legs, cramps and restless legs. These symptoms can be accompanied by swelling of the leg. Severe and longstanding varicose veins can give rise to eczema, skin thickening (lipodermatosclerosis) and venous ulcers. The severity of varicose disease is classified according to CEAP classification (clinical, ethiological, anatomical, pathological elements): class 1, telangiectasias, reticular veins and malleolar flare; class 2, varicose veins; class 3, oedema without skin changes; class 4, skin changes such as pigmentation, venous eczema and lipodermatosclerosis; class 5, skin changes with healed venous ulcer; class 6, skin changes with an active venous ulcer.

Varicose vein-related procedures are among the most performed procedures worldwide, with over 60,000 procedures annually in the UK.¹ In majority, these are performed in an elective day-care setting. For years, ligation of the saphenofemoral junction and saphenous vein stripping was the most applied treatment for insufficiency of the great saphenous vein (GSV). In recent years, endo venous treatment techniques are rising, such as endovenous laser ablation (EVLA) and radiofrequency ablation (RFA). Venous thromboembolism (VTE), either as deep venous thrombosis (DVT) or a potentially fatal pulmonary embolus (PE), is the most serious complication in all of these procedures after treatment of varicose veins.

In an editorial in Phlebology from 2007, Abott et al.² discussed the subject of VTE after varicose vein treatment; he pointed out that there is no consensus among surgeons with regard to perioperative thrombosis prophylaxis. Although many hospitals do have a general thrombosis prophylaxis protocol for patients undergoing surgery under general anaesthesia, routine low-molecular-weight heparin (LMWH) prophylaxis is not by any means standard practice for varicose vein surgery.³ Some surgeons apply a single dose of LMWH to all patients (according to a ‘blanket’ protocol); in other hospitals only patients at high risk for VTE are treated (by means of a risk stratification protocol). Arguments for the latter are that these patients are mostly young persons, without extra risk factors who are mobile again within the same day. Moreover, surgeons are somewhat reluctant to apply anticoagulant measures because there always is a certain degree of bruising which is at risk for progression to haematoma or postoperative bleeding. Accounting to a 1995 survey, only 12% of surgeons used a blanket protocol for prophylaxis.⁴ Some used heparin selectively in obese patients, elderly patients or those with recurrent varicose veins, and most did so only for patients with a history of DVT and those on the contraceptive pill. Another survey showed that 1.4% never applies VTE prophylaxis at all in varicose vein operations.⁵ Clinical guidelines by the American ACCP, Scottish SIGN and Dutch CBO all recommend risk stratification after which only patients with risk factors for thrombosis are to be treated with prophylaxis. The most important risk factors are obesity and a history of VTE.

We performed a systematic review of the available literature about VTE prevention in patients undergoing surgical treatment of varicose veins. In particular, we searched for studies on the incidence of VTE after varicose vein procedures and clinical trials comparing one thromboprophylactic method to another, placebo or no treatment. Few studies have addressed precisely the same questions, for that reason a meta-analysis is not possible – merely a review of the current data.

Methods

We systematically searched the online database from PubMed for studies on the incidence from VTE and on thromboprophylaxis in varicose vein surgery. Table 1 shows our search strategy. We applied no limits for language or publication year. This yielded 181 results. For each study, we judged the abstract for relevance followed by a full-text review if applicable. From these 181 results, we included 13 papers for review. In this search, we found mainly retrospective case series on the postoperative incidence of VTE, and three prospective clinical studies, but no randomised trials on thromboprophylaxis (Table 2)

Table 1

Search strategy

(“Trirombosis”[MeSH Terms] OR “thrombosis”[All Fields]) AND (“prevention and control”[Subheading] OR (“prevention”[All Fields] AND “control”[All Fields]) OR “prevention and control”[All Fields] OR “prophylaxis”[AH Fields]) AND (“varicose veins”[MeSH Terms] OR (“varicose”[All Fields] AND “veins”[All Fields]) OR “varicose veins”[All Fields] OR (“varicose”[All Fields] AND “vein”[All Fields]) OR “varicose vein”[All Fields]) AND (“surgery”[Subheading] OR “surgery”[All Fields] OR “surgical procedures, operative”[MeSH Terms] OR (“surgical”[All Fields] AND “procedures”[All Fields] AND “operative”[All Fields]) OR “operative surgical procedures”[All Fields] OR “surgery”[All Fields] OR “general surgery”[MeSH Terms] OR (“general”[All Fields] AND “surgery”[All Fields]) OR “general surgery”[All Fields])

Table 2

Relevant studies

Hagmuller(1992)⁶	Case series of 3300 varicose vein operations with 0.15% DVT and 0.06% PE
Miller et al. (1996)⁷	Case series of 997 patients (1322 legs) operated according to different techniques. DVT in 4 cases (0.3%) and PE in 1 patient
Bounameaux 1996⁸	Retrospective series of 1063 Strippings with 6 cases of PE (0.56%)
Critchley et al. (1997)⁹	Retrospective study of 973 legs in 599 patients. Three cases of DVT (0.5%) and 1 PE
Gillet et al. (1997)¹⁰	Prospective study with an incidence of DVT of 3% in 180 legs in 154 patients after short saphenous surgery
Puttaswamy et al. (2000)¹¹	Small study using duplex ultrasound reporting a DVT incidence of 5% despite use of thromboprophylaxis. Bilateral procedures were shown to have a higher risk than unilateral (16 versus 1%)
Enoch et al. (2003)¹²	Retrospective review of 2186 patients who underwent varicose vein treatment of which 1283 received thromboprophylaxis because of risk factors and 903 did not. Nevertheless, 4 patients had a VTE in the prophylaxis group
Van Rij et al. (2004)¹³	Prospective study of 377 patients by whom a DVT incidence of 5.3% was found with duplex ultrasound. In the prophylaxis subgroup the DVT incidence was 5.7%. There was no PE
Mundy et al. (2005)¹⁴	Systematic review of 13 case series of EVLA with one DVT all-together
Knipp et al. (2008)¹⁵	Case series of 460 legs in 364 patients treated with EVLA, or EVLA + phlebectomy or ligature of perforating veins. DVT rate was 2.2% in the combination group and 0 in the group of EVLA solely
Van den Bos et al. (2009)¹⁶	Systematic review of adverse events after EVLA, with a DVT incidence of approximately 1%. Author's case series of 500 EVLAs with 3 DVTs of which one also developed PE
Marsh et al. (2010)¹⁷	Retrospective analysis of 2470 cases of RFA under general anaesthesia and 350 of EVLA under local anaesthesia. DVT incidence was 0.7% post-RFA and 1 % post-EVLA
Sutton et al. (2012)¹⁸	Retrospective analysis of Hospital Episode Statistics data to establish the incidence of VTE following varicose vein treatment. VTE incidence 0.51%

DVT, deep venous thrombosis; VTE, venous thromboembolism; EVLA, endovenous laser ablation; RFA, radiofrequency ablation; PE, pulmonary embolism

Results

The incidence of VTE after varicose vein surgery remains unclear. Generally it is assumed that it is less than 1%.⁷ Regrettably, there are no data from randomised studies available. In a series of 3300 varicose vein procedures, Hagmuller⁶ found a DVT incidence of 0.15%. Critchley et al.⁹ stated it was slightly higher, at 0.5%. The group of Bounameaux⁸ from Geneva reported six cases of pulmonary embolism (diagnosed clinically) in a series of 1063 Strippings during a 10-year period (0.56%), which is a rate comparable with the incidence they found in their abdominal procedures. A study by Enoch from 2003 is also interesting: 2186 patients who were operated for their varicose veins in day-care over a four-year period were analysed retrospectively.¹² Of this group, 903 patients did not receive thromboprophylaxis nor did they develop a VTE during three months follow-up. The remaining 1283 patients were treated prophylactically because they had thrombosis risk factors, but four patients developed a VTE nonetheless. In 2005, Mundy published a systematic review on 13 case series of EVLA between 1996 and 2005.¹⁴ Only one case of DVT was reported herein, in a patient with polycythaemia vera. Four years later, van den Bos et al.¹⁶ performed another systematic review focusing on adverse events associated with EVLA and found DVT to occur in approximately 1% of patients. In their own series of 500 EVLAs there were three patients who developed DVT after EVLA of the GSV), one of which resulted in PE. It is suggested that incorrect positioning of the laser tip, using general or epidural anaesthesia instead of tumescent anaesthesia that disallows immediate ambulation after the procedure, and pre-existing coagulation disorders increase the risk of DVT.¹⁹ In only two of the studies analysed by van den Bos a single dose of LMWH prophylaxis was administered to all patients.

Marsh et al.¹⁷ performed a retrospective analysis of 2470 cases of RFA under general anaesthesia and 350 of EVLA under local anaesthesia in 2010. Post-RFA, DVT was identified in 17 limbs (0.7%); post-EVLA four DVTs were found (1%). A retrospective case analysis by Knipp et al.¹⁵ from 2008 was not included in this review; it concerned a series of 460 legs in 364 patients who were treated with EVLA or a combination of EVLA with phlebectomies or ligature of perforating veins. DVT rates were 2.2% for the combination of EVLA and phlebectomy or perforantectomy and 0% in the group of only EVLA. In this study, high-risk patients (stratified by protocol) received a single dose of thromboprophylaxis perioperatively.

Very recently, Sutton et al.¹⁸ performed an analysis of their Hospital Episode Statistics data from all patients who underwent varicose vein surgery between 2006 and 2007 (both open and endovenous procedures) to identify those who were re-admitted because of DVT or PE. The overall VTE incidence was 0.51% and was highest with subgroups that had bilateral redo surgery, short saphenous vein procedures or a combination of EVLA and phlebectomies.

However, in all the aforementioned studies DVT was diagnosed on the basis of clinical signs and symptoms, and not systematically detected by means of duplex ultrasound, which has a much higher sensitivity for finding a thrombosis.²⁰ Puttaswamy et al.¹¹ used duplex imaging in a small study to analyse the incidence of DVT after varicose vein surgery. They reported an overall incidence of 5% despite use of thromboprophylaxis. Bilateral procedures were shown to have a higher risk than unilateral (16% versus 1%). Gillet et al.¹⁰ reported an incidence of DVT of 3% in a follow-up study of 180 legs after short saphenous surgery. In 2004, van Rij et al.¹³ performed a prospective study in New Zealand in an attempt to determine the incidence of both clinical and subclinical DVT after varicose vein surgery. Every patient was analysed for DVT using duplex ultrasound, which was performed pre- and postoperatively by 377 patients. Postoperative DVT was diagnosed in 20 persons (5.3%), an incidence much higher than assumed until that moment. Only eight of these were symptomatic DVTs, and none of the patients developed symptoms of pulmonary embolus. From the 20 DVTs, 18 were limited to the calf veins. There was no propagation of thrombi, and after one year half of the DVTs had disappeared without remaining deep venous insufficiency. Application of thrombosis prophylaxis was left to the discretion of the surgeon. In all, 64.7% of the patients received a single dose of LMWH subcutaneously; nevertheless still 5.7% developed a DVT. Therefore, it remains to be seen if a single dose of LMWH is sufficient as DVT prophylaxis, or if it is necessary to treat for a longer period of time. In conclusion, Van Rij found that the incidence of DVT after varicose vein surgery was higher than assumed on basis of the literature, because in the past clinically insignificant DVTs went by unnoticed and thus would not be registered. However, the DVTs found in this study only had minimal short- and long-term clinical consequences.

Discussion

Both the short- and long-term consequences of DVT can be overwhelming. Post-thrombotic syndrome has enormous morbidity and costs associated with it. Losing a patient to pulmonary embolism after varicose vein treatment is inacceptable. The evidence presented in this review is of low quality and derived mostly, except for three studies, from retrospectively analysed case series. VTE was diagnosed on clinical grounds and not systematically traced in every patient, except by Puttaswamy Gillet and van Rij. Their prospective studies showed that the true incidence of DVT might be 5–10 times higher than expected on a clinical basis. Furthermore, about 5% of the patients receiving prophylaxis still developed DVT. This raises the question whether one preoperative dose of subcutaneous LMWH is sufficient to prevent a DVT, even after short-stay surgery, especially if risk factors are present. The optimal duration of treatment might be longer, for instance a period of one week. It is recommended that patients with risk factors, especially if multiple, should be considered for extended prophylaxis.

Van Rij et al. reported that only eight of a total of 20 DVTs were symptomatic and none became PE. Still the number of patients they analysed is relatively low, and varicose vein surgery is very common. With enormous numbers of varicose vein-related procedures worldwide, there might be considerable morbidity and even mortality of VTE. Like Van Rij suggested, routine postoperative duplex ultrasound scanning is recommended after 2–4 weeks.

Although LMWH have been the standard for thrombosis prophylaxis for many years, the need for subcutaneous injection is a disadvantage. The new group of oral anticoagulants, such as dabigatran, rivaroxaban and apixaban, deals with this disadvantage and has proven for other indications to be equal to LMWH or warfarin. For this reason, future research by our own group will focus on thromboprophylaxis with new oral coagulants. We need reliable data on the incidence of DVT after varicose vein surgery, and the risk reduction of thromboprophylaxis has until this moment not been studied in a randomized controlled trial. We are currently working on a study to evaluate the efficacy and safety of one of the new oral anticoagulants versus placebo, in patients who underwent surgery for varicose veins. Treatment will be continued for seven days. After 2–4 weeks, a systematic, bilateral compression ultrasound will be done in all patients. An independent adjudication committee blind to treatment assignment will review all suspected venous thromboembolic events, including asymptomatic DVT, all deaths and all bleeding events.

It has been argued that because of the low incidence, the number of ‘healthy’ low-risk patients needed to treat to avoid the development of one DVT is likely to be high and not cost-effective. The results of the duplex-controlled studies indicate that DVT occurred in 5% of patients undergoing varicose vein surgery and we hypothesize that prophylaxis with one week of a new oral anticoagulant reduces this to at least 2.5%. The absolute risk reduction is 5–2.5% = 2.5% and the number needed to treat is 1/2.5% = 40. In other words, we would need to treat 40 patients prophylactically to prevent one from developing DVT. Our study will attain sufficient statistical power if we include 1967 patients in the two groups together (I; 0.05, II; 0.8).

In conclusion, more data on the incidence of VTE, and the need for postoperative thromboprophylaxis are necessary to formulate evidence-based clinical guidelines. Therefore, high-quality randomized clinical trials, with high numbers of included patients, and ideally comparing prophylaxis to placebo are warranted.

Funding

This research received no specific grant from any funding agency in the public, commercial, or not for-profit sectors.

Footnotes

Conflict of interest

The authors have no conflicts of interest to declare.

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