The treatment of venous malformations with percutaneous sclerotherapy at a single academic medical center

I would like to thank to the authors for sharing their unique experience with “ethanol sclerotherapy” of venous malformations (VM), a controversial topic.¹ Based on a meticulous analysis of the treatment outcomes, including dreadful complications, the authors demonstrated that ethanol can serve as a first line, and perhaps even as the gold standard treatment for VM.

Ethanol precipitates the protoplasm, denudes the endothelial cell from the vascular wall, and fractures the vascular wall to the level of the internal elastic lamina, yielding permanent and irreversible damage which can be curative. ² Indeed, (absolute) ethanol is the only scleroagent demonstrated to minimize the inherent risk of “recurrence” in congenital vascular malformation (CVM) lesions.

However, as the authors appropriately emphasize, ethanol is not an innocuous scleroagent. Its use demands sufficient precaution. Extravasation of ethanol causes significant collateral damage to surrounding tissues/organs that may range from minor skin bullae/necrosis to massive soft tissue/muscle necrosis and serious nerve damage. When a significant amount of ethanol is allowed to reach to the lungs, pulmonary hypertension will develop either by pulmonary arterial spasm or extensive micro-thromboembolization. This can lead to cardiopulmonary arrest, which may be fatal.

Given these risks, ethanol is known to be the most dangerous scleroagent used for CVM management, and explains why it has been so controversial, despite its chance of “cure” since its ambitious introduction over two decades ago.

Nevertheless, ethanol remains the de facto choice for sclerotherapy, especially for AV malformations (AVM). This is because AVMs are the only potentially life if not limb threatening lesion among the CVMs, so that limited extents of complications and the morbidity of ethanol have been accepted as an inevitable cost in exchange for the excellent and often “curative” long-term outcomes which has not been achieved with any other agent. ³

Indiscriminate use of ethanol, without appropriate indications, has done much more harm than good. These costly lessons taught us that ethanol mandates proper use, as the authors precisely reiterated, in order to minimize if not avoid complications. That has been the price to pay for the change to permanently damage these embryonic tissues, which possess mesenchymal cell characteristics with the potential to grow. Thankfully, most of the complications occurred during the initial learning curve. With proper use, ethanol is the most efficacious agent with drastically reduced complication rates in the setting of AVMs.

VMs, in distinction to AVMs, seldom become a life/limb threatening condition and thus the use of ethanol has been found too costly to justify its use in this setting. ⁴ This is why many leading institutes/groups no longer consider ethanol as the first option for VM management. This concern has changed the use of ethanol from a first-line to a second-line treatment, except for certain circumstances such as a recurrent lesion. The author agrees with this fundamental change in thinking regarding VM management that has occurred over the last decade: “VMs and AVMs are as different as apples and oranges” and agree with the new approach to utilize a detergent-based sclerosant, which had been considered second best, as the first-line treatment for ordinary VMs, particularly for those in the mucocutaneous junction (e.g. lip), and those involving the mucosa/skin (e.g. tongue, oral mucosa). ⁵

The first aim of VM care is symptomatic control rather than the “cure,” and if the VM lesion should recur following sclerotherapy, repeat treatment is easily done as opposed to with the recurrent AVM lesion. Detergent-based scleroagents are the perfect option to deliver acceptable treatment outcomes, especially for VM lesions associated with high risk when treated with ethanol (e.g. nose, face). ⁶

Unfortunately, this new first-line option with detergent sclerosants are destined to recur, based on our experience, in the range of 30% or more within two years. Therefore, we try to convince colleagues that ethanol is still the ultimate agent for selected VM lesions (e.g. recurred lesion), but should be limited to use only by those with great expertise.

Thus, I couldn't agree more with the authors' timely warning regarding the proper use of ethanol for VM, with appropriate precautions.

I also would like to emphasize the chronic morbidity that can occur from ethanol therapy, which the authors lightly touched on. In particular, progressive muscle contraction (e.g. Achilles tendon shortening) has developed following successful ethanol therapy of infiltrating intramuscular VM lesions. A fibrotic contraction of the calf muscle has infrequently had a devastating impact on quality of life, with not only mechanical dysfunction of the ankle/foot but also serious hemodynamic derangement resulting from dysfunctional calf muscle contraction.

Finally, I would like to call attention to the “pain” known as a hallmark for VM, which is a hidden warning for serious potential of “coagulopathy.” Although the authors wisely considered this pain as a major indication for treatment of VMs, they failed to note that may herald an ongoing intravascular coagulation process known as “localized intravascular coagulation (LIC).” ⁷

The extratruncular type of VM lesion consists of an amorphous cluster of tortuous, ectatic venous structures with a vessel wall deficient of smooth muscle cells, which is the outcome of defective development in the early stage of embryogenesis. The slow venous flow through this lesion results in blood stagnation, which precipitates continued activation of the coagulation cascade and leads to the production of thrombin and conversion of fibrinogen into fibrin. This activation phenomenon within VM lesions was named LIC.

Initial coagulation is soon followed by fibrinolysis, which generates elevated levels of fibrin degradation products, including plasmin derived D-dimer epitopes. This complex hemopathologic pathway underlines the pathogenesis of LIC that characterizes this unique coagulopathy associated with VM.

Nevertheless, this unique condition associated with VMs has been grossly neglected and not properly recognized. This is despite the fact that LIC is often combined with a clinically significant consumptive coagulopathy, triggering uncontrollable if not serious bleeding during surgery as well as endovascular procedures for sclerotherapy. Therefore, anticoagulation therapy should be seriously considered when the lesion is bad enough to require interventional procedures.