Therapy methods — Venous malformation

The choice of therapy is based on the appearance and symptoms of the particular venous malformation and can therefore be different over the course of a life. Complete removal is usually not possible. The starting point of treatment is a comprehensive assessment of the vascular malformation by the physician and detailed consultation of the affected person. Only then can a strategy be agreed upon and, depending on the extent of the venous malformation, this should be pursued throughout the individual’s lifetime. Although smaller venous malformations can be adequately treated by one invasive treatment, a large number of patients require repeated treatments. Patients are often young play a central role because over time they get to know their body, their very specific malformation and the effects of the therapy methods. The more extensive the malformation is, the more important it is that the patient takes an active role in determining therapeutic steps. The doctor and/or the treatment team should give the patient their support. Before discussing the individual procedures, it is important to note that:

• Scientific data on the value of the individual methods is scarce
• Recommendations are often based purely on personal experience
• The individual procedures can complement each other well and are combined
• The level of treatment success cannot be readily predicted

As shown in the table below, a distinction is made between conservative and invasive treatment methods:

The role of a comprehensible explanation of the disease cannot be stressed enough. It is a great help for the patient to learn details about the disease: general information about congenital vascular malformations and specifics about their own condition. On the basis of this information, the therapeutic goal can be determined and accepted.

If there is severe discoloration of visible skin areas, water-resistant creams that cover the discoloration well may be useful. Under the guidance of cosmetic specialists the patient becomes familiar with appropriate products and make-up techniques of camouflage.

Compression therapy with individually tailored compression stockings is indicated on the extremities and trunk to relieve congestion and swelling. Compression is particularly effective with subcutaneously localized venous malformations. If worn consistently during the day, it slows down the increase in volume over the years, although it does not bring about regression of the venous malformation. As a rule, compression class 2 (25–40 mmHg) is recommended for adults, which represents a good compromise between effectiveness and wearing comfort. In severe cases, affected individuals also benefit from a stronger stocking (compression class 3, 45–60 mmHg), which can be worn for hours as required. Sometimes it is necessary to prescribe the lighter compression class 1 if this increases compliance or,  in the case of small children, hydrostatic pressure is lower and body growth should not be inhibited. It is also possible to combine a long CC2 stocking with a short CC1 stocking, so that a greater effect is achieved on the lower leg. There are no rigid rules about the extent and duration of compression therapy. Adjustments according to activity, ambient temperature and daily condition are useful. It is not necessary to wear the stockings at night. Appropriate care of the skin to prevent dehydration must be taken.

In view of the loss of elasticity and growth, the compression garments (with a spare pair for hygiene reasons) should be replaced at least every six months. In the case of custom-made products, it may be advisable to contact specialist workshops. These centers have special expertise in the care of different parts of the body, even if they show signs of accompanying overgrowth or undergrowth.

Congestion symptoms usually increase during the day, so that intermittent elevation of the affected areas provides relief. It is important to benefit from the appropriate possibilities, e.g., at school or at work. A resting period while lying down or a brisk walk in between can help to alleviate the symptoms.

Particularly in the evening hours, the congested soft tissue causes unpleasant sensations which can disturb the patient’s ability to sleep. Many patients then benefit from cooling measures such as a shower, the application of a cooling compress or a decongestive massage.

Physiotherapy (PT) plays an important role among the conservative therapy methods, as it has a corrective effect on functional disorders of the locomotor system. PT should therefore be used early and consistently. Unfortunately, there are no specific exercises for congenital vascular malformations. In addition, therapists are often uncertain if an extremity is affected by extensive venous malformation. The visible vascular convolutes and segmental growth disturbances are unfamiliar, so that therapists are hesitant about instructing the patient on  muscle strengthening and joint mobilization. It makes sense for the doctor and physiotherapist to discuss the respective findings and decide on the resulting exercise requirements. The aim is to strengthen the muscles and improve joint mobility, for which patients should be given exercises to do at home. A 45-minute exercise session a week, as approved by most health insurance companies, is not sufficient. The patient and/or parents should be made familiar with the exercise plan and take on the role of the physiotherapist in everyday life.

Closely related to physiotherapy are the sporting activities during leisure time. The type of sport should be based on the parts of the body affected and on the age of the patient. At the same time, the sporting activity should be fun, so that it will be practiced. For a small child, the playground, swimming pool, scooter, trampoline and a ball will define the sporting environment. It is important that the child is introduced to physical activity as an enjoyable thing. Schoolchildren can join a nearby sports club, ideally together with friends. Running sports, ball games and cycling are recommended if one leg is affected. Table tennis, apparatus gymnastics, rowing and climbing are useful for venous malformations affecting the arm. Similarly, parents can discover hiking, cycling or canoeing as a shared, family event on weekends or holidays and thus promote the joy of physical activity.

Teenagers and adults are even allowed to do sports at a competitive level: Marathon runs, for example, are still possible, despite very extensive venous malformation of the leg. In addition to strengthening the musculoskeletal system and increasing physical performance, the sport boosts self-confidence, reduces anxiety and supports social integration.

Analgesics, anticoagulants and in selected cases immunomodulators as well may be indicated in the treatment of venous malformation. Painkillers should be prescribed when a pain-free daily routine cannot be achieved by other measures such as compression, exercise and cooling. As a rule, short-term, on-demand analgesia is sufficient for venous malformation. Relatively acute, stabbing pain occurs with thrombophlebitis and subsides within a few days. Non-opioid analgesics are well tolerated and can be taken provided the maximum daily dose is not exceeded. The prerequisite is, of course, that the correct diagnosis is made by the attending pediatrician or family doctor.

Anticoagulation with coumadin, direct oral anticoagulants (DOACs) or heparin are indicated in cases of recurrent thrombophlebitis or thromboembolism. The duration of anticoagulation depends on the symptoms, so that a shorter duration than in primary thrombophlebitis or thrombosis is usually sufficient. Long-term use over several years should be avoided because of the side effects such as osteoporosis and bleeding tendency. In that situation it is more appropriate to reduce the volume of the malformation by invasive therapeutic procedures. The differential indication for anticoagulation in mostly young patients with venous malformations should be established or evaluated at an appropriate interdisciplinary center.

The immunosuppressant drug sirolimus has been used in selected cases of venous malformations for a few years. It can potentially prevent progression of the clinical picture in the case of rapidly progressive segmental overgrowth and bleeding of large-volume vascular malformations that cannot be controlled in any other way. In view of the relevant side effects, in Germany it is only used in the context of clinical studies at a few hospitals. This will provide important insights into this promising and new therapeutic approach in the coming years.

Understandably, extensive venous malformation can be a significant burden for the affected individual and those closest to them. It is all the more surprising to find that the majority of patients and their families accept the disease and the associated challenges if they are properly informed and advised. In rare cases, however, the disease can also favor the development of depression and neuroses, which can make it difficult to treat the malformation in the long term. Augmenting the therapeutic team by introducing a psychotherapist is then necessary and should be considered at an early stage.

The presence of a venous malformation alone is not sufficient reason for invasive therapy. The indication exists when the symptoms cannot be controlled conservatively or when functional and developmental impairments or other complications are to be expected. It is usually not possible to completely eliminate a large, complex vascular defect, even after multiple therapeutic invasive sessions.

After the indication has been reviewed, the therapeutic goal must be formulated precisely and honestly before treatment. It should be clear to everyone involved that:

• Pain and functional impairments are to be reduced
• Future complications should be avoided
• The extent of the success of the therapy cannot be completely predicted
• The venous malformation can rarely be completely eliminated
• Usually several treatment sessions may be necessary
• Recurrences or deterioration of a residual portion of the venous malformation may occur

This interventional therapeutic procedure is the method of choice in the treatment of venous malformations because of its relatively low invasiveness, its simplicity and its effectiveness. The injection of a sclerosing agent causes inflammation of the vascular endothelium, leading to obliteration of the venous malformation so that it can no longer fill with blood. Congestion and phlebitis can thus no longer occur. The resulting scarred connective tissue is inactive and remains in the body without any consequences. Large-lumen malformations with numerous branches require the repeated injection of large quantities of sclerosing agents. Several puncture sites and closely spaced treatment intervals are necessary to ensure that a sizeable area is sufficiently “dried out”. Otherwise there is a risk that an initially sclerosed venous malformation will re-open by reperfusion from neighboring regions (= real recurrence).

The more extensive the venous malformation, the more important the strategic approach is. It is not the easily accessible parts, but the parts causing symptoms or potentially leading to complications that must be addressed first. The combination of findings from physical examination and cross-sectional imaging provides the basis for this. It is helpful to let the patient mark the tissue areas on the skin that cause the most complaints. The underlying venous malformation represents the target tissue for the invasive therapy. Since puncture and sclerosing agents are painful, it is recommended that the procedure be performed under general anesthesia for children and adolescents. Treatments on the neck and face or with pure ethanol will often be performed under general anesthesia, even in adults. After safe intraluminal placement of the puncture needle, a few ml of an i.v. contrast medium are injected: this allows the spread, flow paths and flow dynamics to be recorded, communicating veins to be identified and the needle position to be verified.

The required amount of sclerosing agent, estimated by means of the CM injection, is injected through the same needle. In doing so, it is important to observe whether there is rapid CM passage into the healthy venous system and whether a relevant communicating vein can be identified. If this is the case (from experience in approx. 10% of cases), the injection must not take place because it could trigger a deep vein thrombosis. The communicating vein must then be closed. Depending on the depth, the needle can be placed under digital or sonographic control. The effectiveness of sclerotherapy increases when the vessels are bloodless, so the affected part of the body is elevated whenever possible. This is naturally easier on the extremities than on the trunk or face.

Postoperative care includes cooling, analgesia, temporary anticoagulation if necessary, and compression if anatomically possible. The duration of pain medication depends on the individual needs and can last from one to three weeks.
Compression after the intervention is recommended for a few days but may be lifelong: validated data are not available. Studies with regard to the sclerosing agents to be used are also of little value. High percentage ethanol, sodium tetradecyl sulfate (STS), polidocanol liquid or foam, gelled alcohol and bleomycin are used for the treatment of venous malformations. These agents differ, sometimes considerably, in terms of effectiveness, side effects and cost. Regional availability and personal experience play a major role in the selection. In Germany gelled alcohol and polidocanol 3% in foam form, including in combination, are frequently used.

Surgical removal used to be the only therapeutic option for venous malformations and has now been replaced by sclerotherapy as the method of choice, regardless of the localization. Alongside endovascular procedures (radiofrequency ablation and laser therapy), surgical treatment has nevertheless retained its importance in the treatment of truncular, large-lumen vascular malformations in the subcutis. In view of the increased risk of bleeding, insufficient resectability and damage to muscles and nerves, the benefit of resection of subfascially located venous malformations must be questioned in many cases. However, if the  indication and handling are correct, sclerotherapy and resection complement each other in such a way that they can be used in combination for some cases. Naturally, it is also true for surgical resection that the indication is justified not by how easy it is to perform but by the symptoms alone. Whether resection of an asymptomatic venous malformation in childhood improves the prognosis is postulated by some authors, but is not sufficiently proven. Conversely, other surgeons recommend treatment only after the end of growth age, but the validity of this approach is not proven either. As stated above, treatment should be given regardless of patient age when there are symptoms that cannot be controlled conservatively and when developmental disorders are to be expected.

Surgery for venous malformations is fundamentally different from varicose vein surgery and places special demands on the surgeon. Venous stripping, which is common in surgery for truncal varicosis, would cause heavy bleeding and would inadequately correct the malformation. The very vulnerable vessel wall, irregular side branches, large caliber changes, spread across layers and the abundance of blood in the surrounding soft tissue caused by small fistulas are special features of venous malformations and require large accesses as well as meticulous and time-consuming preparation. After identification and preoperative marking of the clinically relevant body sections, circular dissection of the vascular convolutes is performed through long enough skin incisions.

Side branches and deep connections are ligated or treated with suture ligatures. The large-caliber malformations can thus be removed with little blood loss. The necessary, careful preparation of an area of 5 x 5 cm can take up to an hour, which must be taken into account when planning the procedure.

It is therefore more appropriate to address a few highly painful areas instead of resecting the malformation throughout the entire length of the leg, for instance. The procedure concludes with particularly meticulous hemostasis and layered and tension-free wound closure. Compression bandages, elevation of the extremity and cooling have a pain-relieving and decongestant effect. Depending on the size and location of the wounds, early mobilization (if necessary on crutches) is accompanied by analgesia as required.

Vascular surgical reconstructions of larger body veins such as the inferior vena cava or pelvic veins are hardly ever indicated for venous malformations. As a rule, congenital venous dysplasia or aplasia is functionally less significant on account of the formation of bypass circulation. Intraoperative injury to important collaterals must be avoided at all costs.

The application of lasers leads, via thermal coagulation, to destruction of the vessel endothelium and scarring of vessels. Application can be percutaneous, interstitial and intraluminal, whereby different tissue depths can be reached depending on the laser wavelength and mode of application. Most published experience relates to percutaneous application, which allows  intracutaneous and subcutaneous vessels to be treated up to a depth of 10 mm with compression. The indication for percutaneous laser therapy thus exists for combined capillary-venous malformations (CVM) in the facial region, especially if lips, eyelids, auricles and nostrils are affected. The treatment is time-consuming and should be performed by an experienced therapist. The choice of the right wavelength, intensity and duration of the laser pulse is crucial for the success of the treatment. In addition, accompanying damage to the skin, retina and nerves should be avoided by covering and cooling. Laser treatment should therefore be reserved for centers with extensive experience in congenital vascular malformations.

In interstitial application, the light-bearing laser fiber is introduced into the malformation tissue via a cannula, activated and slowly retracted under ultrasound control. However, the effectiveness of this procedure can be limited, so that it is generally not a therapeutic option. In the intraluminal application, the light-bearing fiber introduced via a puncture needle is also slowly retracted through the venous malformation under ultrasound control. If the malformation has a tubular morphology with a constant caliber, the entire endothelium can be adequately and permanently damaged by the energy released. In irregularly shaped vessels, however, only temporary coagulation of the blood is achieved, depending on the lumen size of the vessel. The endothelium is mostly intact, so that reperfusion is often detectable by the following day. Another disadvantage is that the laser beam can perforate the vessel and cause painful nerve lesions and hematomas.

In view of the irregular form of a sponge-like venous malformation, however, it is doubtful that a distinction can always be made between interstitial and intraluminal laser application. In this case it is not possible to keep the fiber intraluminal as in a tubular venous malformation, e.g., a marginal vein. Instead, perforation with the puncture needle straight through the honeycomb-like tissue always takes place and effectiveness is hence very variable.

Comparable to intraluminal laser, radiofrequency (RF) therapy involves inserting a probe into the venous malformation after puncture under ultrasound control. The catheter tip touches the endothelium at several points, where a controlled amount of energy along the RF probe tip then causes heating of the vessel wall (90°–120°C). This results in denaturation and destruction of the tissue. Infiltration of surrounding soft tissues with liquid (tumescence solution) protects them somewhat from the heat. This measure is particularly important in preventing nerve damage. Depending on the findings, the probe can be passed through the malformation several times, thus achieving complete lumen occlusion. This procedure is hence indicated for larger tubular venous malformations (e.g., marginal veins) as well as for combined lymphatic-venous malformations (LVM). Individual case series prove the effectiveness on the face, neck and extremities. A problem with this endoluminal procedure is that the relatively rigid probe tip is often difficult to pass through the thin-walled and rarely straight venous malformations, which are often perforated. This reduces the effectiveness and increases the risk of injury to adjacent structures. In this situation, special RF probes that can be advanced over a previously inserted guide wire are helpful. The available data do not yet allow a final evaluation of this therapeutic option.

The catheter-assisted insertion of thrombogenic materials such as coils, glue and plugs is a possible option in the therapy of large-lumen and deep venous malformations. The main purpose of this method is to close large veins communicating with the deep vein system.

Although this does not “dry out” the entire malformation, it can be useful to close the communication of a particularly large-lumen part of it with the deep venous system. Subsequent sclerotherapy can then be carried out effectively and without complications, without the sclerosing agent being able to drain off. The embolization is intended to reduce the blood volume of the affected body part and thus the associated, troublesome tightness. However, the radiologically detectable success of the intervention is not always reflected in the clinical outcome.

After successful embolization, the symptoms can be very varied: improved, unchanged or even worse. The value of embolization should not be diminished by this statement. Instead it means that experience with the indication still needs to be gathered.

With very few exceptions, transarterial catheter embolization to occlude arteriovenous fistulas into the venous malformation is not indicated and should be avoided.

In conclusion, it can be said that, thanks to the development of interventional procedures, relevant progress has been made in the treatment of large, painful and quality of life-limiting venous malformations. Although sclerotherapy is the method of choice in many cases, the other methods presented here also have their place in the armamentarium of venous malformation therapy. It is important to ensure the correct indication is established. This can best be done in an interdisciplinary center, where there is experience with several different invasive therapeutic options.