Cardiovasc Intervent Radiol
DOI 10.1007/s00270-015-1085-4
REVIEW
Management of Low-Flow Vascular Malformations: Clinical
Presentation, Classification, Patient Selection, Imaging
and Treatment
Ian McCafferty1
Received: 13 October 2014 / Accepted: 2 February 2015
 Springer Science+Business Media New York and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) 2015
Abstract This review article aims to give an overview of
the current state of imaging, patient selection, agents and
techniques used in the management of low-flow vascular
malformations. The review includes the current classifica-
tions for low-flow vascular malformations including the
2014 updates. Clinical presentation and assessment is
covered with a detailed section on the common sclerosant
agents used to treat low-flow vascular malformations, in-
cluding dosing and common complications. Imaging is
described with a guide to a simple stratification of the use
of imaging for diagnosis and interventional techniques.
Keywords Venous intervention  Paediatric
interventions  Embolization  Peripheral vascular 
Vein  Vascular malformations
Introduction
Vascular malformations are a complex group of develop-
mental abnormalities that present significant challenges in
diagnosis and management. The clinical presentation can
range from an asymptomatic birthmark to fulminant car-
diac failure. The diverse nature of symptoms associated
with vascular malformations and their rarity means that
patients have often seen multiple specialists before the
correct diagnosis is made. Patients often undergo unnec-
essary biopsy, surgery and to some degree imaging, which
& Ian McCafferty
ian.mccafferty@uhb.nhs.uk
1 The aim of this article is to address a practical classifi-
Queen Elizabeth Hospital Birmingham (QEHB) &
Birmingham Children’s Hospital (BCH), Mindelsohn Way,
Edgbaston, Birmingham B15 2GW, UK
in some cases, can mean that the vascular malformation
grows and can affect the outcome of further treatment. The
management of this complex group of patients should
therefore be undertaken within a multidisciplinary team.
The exact make-up of the multidisciplinary team depends
on the availability and interest locally; however, in our
experience, the team has typically included interventional
radiologists, plastic surgeons (craniofacial and peripheral),
maxillofacial surgeons and dermatologists.
Vascular malformations are developmental anomalies
that are a result of arrested development at various stages
of vasculogenesis or angiogenesis. These can be localised
of diffuse and are commonly sporadic. They are present at
birth, although they may not become apparent until ado-
lescence or adulthood. They affect males and females
equally and persist throughout life, typically with a fluc-
tuating course of symptoms that can be accentuated by
pregnancy. Lymphatic malformations are localised devel-
opmental abnormalities of the lymphatic system, which
results in numerous thin-walled cysts containing lymph.
The cysts vary in size and typical are divided into micro-
cystic (cysts less than 2 cm) and macrocystic (cysts greater
than 2 cm) variants. One of the more complex components
of understanding and managing vascular malformations is
the knowledge of the current accepted terminology to de-
scribe the different entities within the spectrum of vascular
anomalies. A practical classification system that allows a
simple differentiation of the subtypes of vascular anoma-
lies to allow implementation of the correct treatment al-
gorithm is essential. This is then further complicated by the
existence of a number of syndromes that will not be cov-
ered in detail within this review article (see Table 1).
cation and terminology and discuss patient evaluation
(clinical and imaging) and therapeutic options available for
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Table 1 Syndrome based classification
Venous and lymphatic malformation syndromes
Klippel–Trenaunay Syndrome (KTS)
Parkes Weber Syndrome (PWS)
Servelle–Martorell Syndrome (SMS)
Maffucci Syndrome
Proteus Syndrome
CLOVES Syndrome
Bockenheimer Syndrome
Blue Rubber Bleb Naevus Syndrome
Gorham–Stout Syndrome
the different types of low-flow vascular malformations.
The review will include discussion on the agents available
for sclerotherapy, dosage and the techniques available to
aid treatment and improve outcomes. The review will in-
clude commentary on experience obtained running a mul-
tidisciplinary vascular malformation service, with both
adult and children’s craniofacial and peripheral clinics for
over 15 years in both the Birmingham Children’s Hospital
and the Queen Elizabeth Hospital Birmingham.
Classification
In 1982, Glowacki and Mulliken [1] proposed a ‘‘biologi-
cal’’ classification of vascular anomalies based on clinical
behaviour, histology and histochemistry. The classification
was accepted by the International Society for the Study of
Vascular Anomalies (ISSVA) and was updated at the in-
augural ISSVA meeting in 1992. This classification is now
widely accepted, and has help resolve the confusion of
terminology in the field of vascular anomalies. The clas-
sification was updated at the 20th ISSVA workshop in
Melbourne April 2014, incorporating elements of the
Hamburg classification system. Broadly speaking, Glo-
wacki and Mulliken divided vascular anomalies into 2
groups: Vascular tumours (underlying endothelial hyper-
plasia) and Vascular malformations (dysmorphogenesis
and abnormal cellular turnover). Vascular malformations
are further divided into low flow (capillary, venous, lym-
phatic and combined) and high flow (arteriovenous mal-
formations, arteriovenous fistula) (see Table 2).
For completeness, a brief description of the Hamburg
classification [2, 3] is included; it is frequently mentioned
in the malformation literature and it is important to un-
derstand its elements. It was established following the 7th
meeting of the International workshop on vascular mal-
formations in 1988, and clarifies morphological differences
within the vascular malformations subset. These morpho-
logical differences are explained by the timing of arrested
development of the vascular system in various stages of
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I. McCafferty: Management of Low-Flow Vascular Malformations…
angiogenesis (see Table 3). Extratruncal lesions are
theorised to maintain their unique embryological charac-
teristics and ability to proliferate when stimulated by
trauma, menarche, puberty, pregnancy, female hormones
and surgery [4, 5]. They are further subdivided into diffuse
infiltrating and localised limited. Truncal lesions do not
have the embryonic characteristics and hence do not posses
the ability to proliferate.
For the purposes of this review on the management and
outcomes of Low-flow Vascular Malformations (LFVM),
we use the Glowacki and Mulliken classification where
LFVM’s are subdivided into Capillary (CM), Venous
(VM), Lymphatic (LM) and combined lesions. The low-
flow venous malformations have a high recurrence rate,
and management should be considered to be a lifelong
process for symptomatic lesions.
Clinical Presentation
Low-flow vascular malformations have a varied clinical
presentation depending on whether the lesions are focal or
diffuse and which anatomical compartments are involved.
It is not uncommon for patients to have been referred to a
number of different specialities before a correct diagnosis
is made. They have an incidence of approximately 1 in
10,000 [6]. Venous malformations are the commonest of
the low-flow vascular malformations with a prevalence of
1 % in the general population [7].
A detailed history and examination commonly reveal the
diagnosis and can help differentiate from other sinister
differential diagnoses. Clinical features are typically re-
lated to the focal mass and patients predominantly present
with pain and swelling, which is commonly intermittent.
Aesthetic issues are also very common presentation.
Clinical examination can separate high-flow (warm, thrill
and bruit) from low-flow abnormalities, which in turn can
be separated into venous, macrocystic lymphatic and mi-
crocystic lymphatic (see Fig. 1).
Capillary malformations are the most commonly seen.
They are abnormalities of the capillary networks within the
skin and mucosal membranes, which may be isolated or
herald the presence of extracutaneous disease. Examples of
capillary malformations are salmon patches (naevus sim-
plex), port wine stains (naevus flammeus). Port wine stains
occur in 0.3 % of newborns and are part of the clinical
manifestation of a number of syndromes: Sturge–Weber
(SWS); Klippel–Trenaunay (KTS) and Proteus. Capillary
malformations are typically treated with laser therapy.
Venous malformations (VMs) can occur anywhere in the
body but are frequently seen in the head and neck (40 %)
extremities (40 %) and trunk (20 %). They present in any
anatomical location, tissue or organ, are not confined by
anatomical planes and may involve multiple tissue types.
I. McCafferty: Management of Low-Flow Vascular Malformations…
Table 2 ISSVA 1996 classification of vascular anomalies (update ISSVA 2014)
Vascular anomalies
Vascular tumours
Benign
Infantile haemangioma
Congenital haemangioma
Rapidly involuting (RICH)
Non-involuting (NICH)
Partially involuting (PICH)
Tufted angioma
Spindle cell haemangiomas
Epithelioid haemangiomas
Pyogenic granuloma
Locally aggressive
Kaposiform haemangioendothelioma
Retiform haemangioendothelioma
Composite haemangioendothelioma
Papillary intralymphatic
angioendothelioma (PILA)
Dabska tumour
Malignant
Angiosarcoma
Epithelioid haemangioendothelioma
a
Birmingham additions
This is most commonly seen in the periphery, which adds
complexity to their presentation and management and can
affect treatment outcomes. This has lead some groups to
Vascular malformations
High flow Low flow
Arteriovenous malformation (AVM) Capillary malformation (CM)
Sporadic Cutaneous (Port wine stain)
In HHT Telangiectasia (HHT)
In CM-AVM Cutis marmorata telangiectatica congenital
Arteriovenous fistula (AVF) (CMTC)
Sporadic Angiokeratoma
In HHT Venous malformation (VM)
In CM-AVM Common sporadic (VM)
Complex combined malformation Blue rubber bleb naevus syndrome
Capillary–arteriovenous (CAVM) Glomuvenous malformation (GVM)
Capillary–lymphatic–arteriovenous Familial cutaneous and mucosal venous
(CLAVM) malformation (VNCM)
Capillary–venous–arteriovenous (CVAVM) Cerebral cavernous malformation (CCM)
Capillary–lymphatic–venous–arteriovenous Maffucci syndrome
(CLVAVM) Lymphatic malformation (LM)
Common (cystic) LM
Microcystica
Macrocystica
Mixeda
Generalised lymphatic anomaly (GLA)
LM in Gorham-Stout disease
Primary lymphedema
Nonne–Milroy disease
Primary hereditary lymphedema
Complex combined malformation
Capillary-venous (CVM)
Capillary-lymphatic (CLM)
Lymphovenous (LVM)
Capillary lymphovenous (CLVM)
Vascular malformations associated with other anomalies:
Klippel–Trenaunay Syndrome (CM ? VM ± LM ? limb overgrowth)
Parkes Weber Syndrome (CN ? AVF ? limb overgrowth)
Servelle-Martorell syndrome (limb VM ? bone overgrowth)
Sturge–Weber Syndrome (facial ? leptomeningeal CM ? eye ± bone AND soft tissue)
Maffucci Syndrome (VM ± spindle cell haemangiomas ? enchondroma)
Macrocephaly—CM
Microcephaly—CM
CLOVES Syndrome (LM ? VM ? CM ± AVM ? lipomatous overgrowth)
Proteus Syndrome (CM ? VM ± LM ? asymmetrical somatic overgrowth)
Bannayan–Riley–Ruvalcaba Syndrome (AVM ? VM ? macrocephaly ? limb overgrowth)
suggest an additional peripheral limb venous malformation
subclassification to aid management stratification (see
Table 4). The Birmingham peripheral limb classification
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 I. McCafferty: Management of Low-Flow Vascular Malformations…

Table 3 HAMBURG (1988) classification of congenital vascular Table 4 Birmingham classification of venous malformations in
malformations periphery
Congenital vascular malformations (CVMs) Type 1 Localised or superficial Without skin involvement
With skin involvement
Species
Type 2 Fascia or muscle infiltration Without skin involvement
Arterial malformation
With skin involvement
Venous malformation
Type 3 Bone or joint involvement Without skin involvement
Arteriovenous malformation
With skin involvement
Lymphatic malformation
Type 4 Trunk and limb lesion Without skin involvement
Capillary malformation (chest or abdomen) With skin involvement
Combined vascular malformation
Type 5 Diffuse whole limb Without skin involvement
Embryological forms involvement, e.g. Klippel– With skin involvement
Extra-truncular (defects arising at an early stage of angiogenesis Trenaunay syndrome
while the vascular structures are in an undifferentiated state and
presents as clusters of amorphous vascular tissue. High
recurrence rates) position. There is often a history of intermittent bouts of
Infiltrating/diffuse more severe pain, which is secondary to localised throm-
Limited/localised
bosis and thrombophlebitis. VMs often have associated lo-
Truncular (defects arising from pre-existing vascular structures in
calised coagulopathy with low fibrinogen and raised fibrin
the maturation period during later stages of angiogenesis. Low degradation products, which leads to this thrombosis and
recurrence rates) paroxysmal pain [9]. We, and others, have seen growth in
Obstruction/stenosis puberty [10], pregnancy and associated with the oral con-
Aplasia; Hypoplasia; Hyperplasia traceptive pill [4, 11]. Progesterone and oestrogen markers
Stenosis; Membrane; Congenital spur have been shown on endothelial cells of VMs [12]. These
Dilatation and somatic growth factors, which are elevated in puberty,
Localised (aneurysm) have been postulated to stimulate endothelial growth factors
Diffuse (ectasia) causing growth during these times [10]. There is also an
increase in the incidence of thrombophlebitis at these times
due to the increased oestrogen levels. Growth has also been
reported following trauma and partial resection [10, 13]. The
severity of symptoms depends on the size of the lesion,
location and proximity to adjacent structures. Superficial
lesions often exhibit a bluish/purplish discolouration and
can be associated with dilated veins. On examination, the
lesions are characteristically soft, compressible, non-pul-
satile and demonstrate filling on dependency. Phleboliths
can often be palpated in large lesions. Lesions are most
likely to progress during adolescence (75 %) although 25 %
occur in childhood [14].
Lymphatic malformations (LM’s) more commonly affect
the head and neck (48 %) with the trunk and extremities
(42 %) and intra-thoracic/intra-abdominal viscera (10 %).
Fig. 1 Typical clinical features of a low-flow venous malformation 90 % are diagnosed in children younger than 2 years with
that affects skin; blue discolouration of the skin with mass effect that
almost half present at birth [15]. They have 2 typical pre-
exhibits dependency
sentations depending on whether the lesions are microcystic
of macrocystic. Macrocystic lymphatic malformations
[8] is one that separates venous malformations as to whe- typically have cyst spaces [2 cm and appear as soft non-
ther they are localised or diffused; fascia or muscle in- pulsatile masses with normal overlying skin, which are
volvement; bone or joint involvement; trunk extension or present at birth. Lesions do not exhibit dependency and are
whole limb involvement with or without skin involvement. not compressible but demonstrate trans-illumination. Mi-
Lesions within the periphery are more likely to be associ- crocystic lymphatic malformations can infiltrate tissues most
ated with truncal abnormalities. commonly skin and mucous membranes but also affect bone
Most commonly the lesion causes a dull ache accentuated and organs. There is typically numerous vesicles overlying
by activity, extremes of temperature, valsalva or dependent the affected area and associated with expansion, e.g. swollen

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I. McCafferty: Management of Low-Flow Vascular Malformations…
limb. The area covered in a vesicles often bleed tend to leak
small amounts of lymph and are commonly complicated by
episodes of bleeding and infection which can lead to acute
expansion of the affected area. This can lead to serious se-
quelae dependent of the site affected. Lesions are most likely
to progress during adolescence (63.8 %) although 40 %
occur in childhood [16].
Diagnostic Imaging
The vast majority of low-flow vascular malformations
(LFVM’s) can be diagnosed by a detailed history and
clinical examination; typically one can also differentiate
the majority into lymphatic and venous subtypes. Imaging
is therefore there to confirm the diagnosis and extent of
involvement, identify rare but significant differential di-
agnoses and to plan treatment options (conservative, per-
cutaneous sclerotherapy or surgery). Numerous modalities
exist to image patients with LFVM’s; for example, plain
films may show numerous phleboliths associated with a
soft tissue mass and aid the diagnosis of a venous LFVM.
Computer tomography (CT) may also show these charac-
teristics, demonstrate the extent of the lesion as a hypo-
dense or heterogeneous mass, which enhance slowly and
peripherally (LM’s) and homogenously (VM’s) with the
presence of intralesional fat as well as haemorrhage.
However, the most useful imaging modalities for the di-
agnosis and planning of treatment are ultrasound and
magnetic resonance imaging. Diagnostic angiography has
no role in the management of LFVM’s (see Fig. 2). Direct
stick venography will be discussed later.
Ultrasound-B Mode and Duplex
Ultrasound (US) is essential in the management of
LFVM’s. High-resolution linear array transducer
(5–12 MHz) is used first, often, in outpatients to differen-
tiate the lesion from other tumours and confirm the clinical
diagnosis. A malformation typically appears as a low re-
flective or heterogeneous defined mass lesion, which can be
unilocular or multilocular. The cystic areas in LMs are
typically non-compressible, whereas VMs are compressible
(except in thrombosis) and phleboliths can be detected in
20 % (see Figs. 3, 4), which are pathognomonic of VMs
[17]. Duplex US can define the size and help differentiate
VM’s from LM’s by demonstrating low velocity flow
within the lesion, although up to 20 % of VM’s, no flow is
seen [18]. It should be noted that US has limitations with
depth penetration and assessment of associated structures
such as nerves, bone and defining the extent of lesions not
located in the extremities.
US plays a critical role in the assessment of the lesions
to decide on sclerotherapy agents and accessibility with
percutaneous needles. One may choose a different agent if
the lesion is predominantly matrix in nature rather than
contains multiple large cystic spaces. Those lesions with an
abundance of vascular or lymphatic spaces are likely to
benefit more from sclerotherapy. US is also ideal to assess
the presence and patency of the deep and superficial venous
systems prior to sclerotherapy.
Magnetic Resonance Imaging (MRI)
LFVM’s have often been described as ‘‘iceberg lesions’’
[19] as the portion clinically apparent if often only the tip
of the underlying malformation. MRI is the imaging
modality of choice as it has superior contrast resolution
when compared to CT, it can image in a multiplanar
fashion and the lack of ionising radiation is ideal [20, 21].
It has been shown to play a vital role in diagnosing deeper
lesions, categorising the type and determining the extent of
tissue involvement in LFVM’s (muscles, bone, tendons,
subcutaneous tissue and skin) and thereby determine
management options [22–26]. The assessment with MRI
can give prognostic information and should include a de-
scription of the extent—focal, multifocal or diffuse; tissues
involved including joint involvement and evidence of prior
haemorrhage [27]. The degree of muscular involvement,
for example, may be predictive of the risk of contractures
either due to involvement or post-sclerotherapy [28].
The basic underlying principle of MRI is to confirm the
clinical diagnosis and identify the anatomy/extent of the
lesion, in at least 2 orthogonal planes. This allows appro-
priate planning of treatment and outcome prediction. There
are numerous MRI protocols described in the literature but
we optimise imaging to identify slow moving fluid—lymph
or blood. We use fast spin-echo T1-weighted imaging to
define anatomy and the presence of haemorrhage and
haemosiderin (some combine this with gradient-echo T1-
weighted sequences to identify any high flow element) and
fat suppression techniques (either fast spin-echo T2-
weighted or short inversion time inversion recover STIR’s)
to increase lesion detection by suppressing the bright fat
surrounding and within the bright LFVM (see Fig. 5).
These simple sequences can typically diagnose and assess
LFVM’s alone and can also aid differentiation of LM’s
from VM’s with layering within lymphatic macrocysts.
However, it must be remembered that rarely due to ex-
tremely slow flowing blood within a VM sedimentation of
the red blood cells can mimic this (see Fig. 6). The MRI
can also differentiate common differential diagnoses, e.g. a
ranula (see Fig. 7).
The addition of post-contrast imaging with or without fat-
suppressed T1 imaging is useful in differentiating LM’s
from VM’s—LM’s enhance peripherally (see Fig. 8) and
VM’s enhance homogeneously throughout the lesion (see
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 I. McCafferty: Management of Low-Flow Vascular Malformations…

Fig. 2 Low-flow venous malformation demonstrating an arterial signal area with no flow voids and the pre-gadolinium (C) and post-
blush, but no early venous filling pathognomonic of a high-flow gadolinium (D) images demonstrate the typical central enhancement
lesion. A The T2 fat-saturated axial image. B Demonstrates the high of a venous malformation

Fig. 3 Ultrasound of a low-flow venous malformation demonstrating a macrocystic lesion and a phlebolith pathognomonic of a venous lesion
and a matrix rich lesion with very few macrocystic spaces

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I. McCafferty: Management of Low-Flow Vascular Malformations…
Fig. 4 Ultrasound of a low-flow lymphatic malformation demon-
strating a macrocystic malformation (A) and a complex lesion
(B) secondary to haemorrhage
Fig. 5). This is usually performed in a static phase; however,
some authors advocate the use of 3D time-resolved MRA
and rapid dynamic contrast-enhanced imaging to look at
arterial inflow, equilibrium and venous outflow phases [29–
31]. This allows assessment of flow characteristics, anatomy
(including venous drainage) and enhancement [9, 32, 33].
These techniques, however, have a far more important role
in the assessment and management planning of high-flow
malformations. VMs can occur anywhere, and the admin-
istration of contrast is extremely useful in atypical anato-
mical sites to aid the diagnosis (see Fig. 9). Contrast is
paramount when the clinical history and examination is
atypical as the enhancement pattern can help in identifying
the differential diagnoses (see Fig. 10), e.g. tumour [11, 34,
35]. However, this does add significant imaging time and
cost, and may not be required in the investigation of all VM
cases.
Management principles
A multidisciplinary team approach is essential for the ap-
propriate management of LFVM’s. Not all LFVM’s are
amenable to treatment and not every lesion requires
treatment [4]. Indications for treatment include the pres-
ence of troublesome symptoms, e.g. bleeding, pain, aes-
thetics and functional impairment and the presence of
complications, e.g. infection and coagulation issues.
General Measures
1. Explanation of the diagnosis and likely clinical course
2. Custom-made compression garments for VM’s.
3. Treatment of associated complications: infection,
anaemia, thrombophlebitis and localised DIC.
4. Involve other specialities for specific requirements:
orthopaedics for leg length discrepancy or joint
involvement, haematology for coagulation issues.
5. Screening of family members for inherited
malformations.
6. Referral of complicated cases to experienced tertiary
centres where the patient can be treated by an
organised multidisciplinary team.
Observation and Conservative Management
The majority of LFVM’s that are seen in a multidisci-
plinary team require assessment and advice. One explains
the diagnosis, natural history and expected level of risk
related to size, location, depth and proximity to adjacent
structures before considering active treatment [36, 37].
Clinical follow-up, advice regarding thrombophlebitic
events (see Fig. 11), compression bandages and a contact
details suffice in most.
Surgery
Surgery has traditionally been used to treat both LM’s and
VM’s; however, excision based on limited knowledge of
the biology of these lesions has lead to poor surgical out-
comes [36, 38, 39]. There is no role for surgery in micro-
cystic LM’s, although surgery has been frequently used for
macrocystic LMs. There is a high incidence of complica-
tions following surgery (12–33 %), which include airway
obstruction, scarring, haematoma and infection [40–42].
Surgery is never radical at first attempt in these cases and
needs to be staged [43, 44], and recurrence rates are very
high (15–53 %).
Surgical excision can be used for focal VM abnor-
malities, debulking procedures and peripheral malforma-
tions where percutaneous sclerotherapy can have
significant risks of terminal ischaemia. This can lead to
significant functional improvement but an experienced
surgeon treating LFVM’s who understands the risks of
incomplete resection and the proliferative nature of
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 I. McCafferty: Management of Low-Flow Vascular Malformations…

Fig. 5 MRI characteristics of

low-flow venous malformation.
T2 fat-saturated sequences
demonstrate the lesion best (A,
B). This is true for both venous
and lymphatic malformations.
In B, the presence of a small
low signal focus consistent with
a phlebolith (arrow) diagnoses a
venous lesion. And this can be
confirmed with the use of
gadolinium that demonstrates a
central enhancement pattern (C,
D)

extratruncal LFVM’s [37, 45, 46]. Roh et al. demonstrated
a 75 % improvement in patient’s symptoms for debulking
procedures where sclerotherapy had failed or was deemed
unsafe [47]. Surgery is also used following percutaneous
sclerotherapy when treatment has been incomplete or when
aesthetic prejudice requires correction [38]. Recurrence
after surgery is high around 22 % for LFVMs [48].
endothelial linings of LFVMs and induce fibrosis. Each
agent has its own unique technique and safety profile and it
is essential to have a full understanding of these agents in
order to manage these patients. The common agents used
are discussed below.
Treatment Agents

Percutaneous Sclerotherapy
Percutaneous sclerotherapy with ultrasound and fluoro-
scopic guidance is now universally accepted as a treatment
option for both VM’s and LM’s. Sclerotherapy is the only
option available in the poor surgical candidate with ex-
tensive multi-compartment involvement [49]. A variety of
sclerosant agents exist, which aim to destroy the
There are numerous agents described in the literature for
treating low-flow vascular malformations. A number of
these agents are used specifically for either lymphatic or
venous low-flow malformations, although some can be
used in both subsets. For the purposes of this review, only
the commonest agents described in the literature are de-
scribed. These include sodium tetradecyl sulphate, ethanol,
polidocanol and bleomycin [50–58]. It must be noted that

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I. McCafferty: Management of Low-Flow Vascular Malformations…

Fig. 6 MRI of a lymphatic malformation (A, B) in the axilla differentiate LM from VM but in very slow flow venous lesions
demonstrating layering within the lesion macrocysts due to separation layering an also be seen (C, D). This is felt to represent sedimentation
of the proteinaceous liquid. This traditionally has been a feature to of the red cells

Fig. 7 A differential diagnosis

of a low-flow vascular
malformation. Features suggest
a lymphatic malformation with
high signal intensity of the T2
fat saturation sequences and
post-gadolinium the lesion
shows only peripheral
enhancement. The lesion was a
ranula

123

Fig. 8 Typical MRI features of a macrocystic lymphatic malforma-
tion in the left axilla. On the T2 fat-saturated images the lesion is seen
as a high signal intensity lesion due to its static fluid content (A) and
the white arrows demonstrate the peripheral wall enhancement (B)
Fig. 9 An example of a low-flow venous malformation affecting
bone (left acetabulum). An expansile cystic appearances on CT (A),
typical high signal intensity on the T2 fat saturated MRI (B) and
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I. McCafferty: Management of Low-Flow Vascular Malformations…
at present there has been no prospective randomised con-
trolled studies comparing the sclerosing agents currently in
use. There is no consensus as to which sclerosant agent is
best but each agent has its own unique administration
technique and complication profile [59; see Table 5:
Common treatment agents].
Sodium Tetradecyl Sulphate (STS-Fibrovein: STD Phar-
maceutical, UK) Originally 3 % STS was injected per-
cutaneous directly into the malformation typically
following a venogram to outline the abnormality, using a
contrast displacement technique. However, more recently,
foam STS has become the standard treatment with some
evidence suggesting superior sclerotherapy [60], where
microbubbles of air are coated with STS creating enor-
mous increase in the surface area displacing blood from
the lesion and permitting better contact of the agent to the
endothelium [61]. It is the contact with the endothelium
that is important to cause damage. The Tessari technique
[62] is commonly used to create the foam; in this tech-
nique, 2 leur lock syringes are attached via a three-way tap
(see Fig. 12). Neat STS is then mixed with a volume of air
classical homogeneous enhancement following Gadolinium contrast
administration (C, D)
I. McCafferty: Management of Low-Flow Vascular Malformations…
Fig. 10 Low-flow vascular malformations (B) have a typical ap-
pearance on MRI and can confidently be diagnosed with an
appropriate accompanying clinical history, however, other conditions
and agitated through the three-way tap in typical mixes of
1:1 and 1:2 (STS:air) with or without contrast (iodinated or
lipiodol). The STS to air mix is only important for the
stability of the foam [63], although it does affect the
bubble size, and a compromise has to be made between
stability, STS concentration and amount of air adminis-
tered. It should be noted that STS is deactivate by a
relatively small volume of blood; 0.5 ml of blood will
deactivate 1 ml of 3 % STS significantly reducing the
systemic effects [64].
A robust hydration protocol can significantly reduce the
risk of renal complications [65, 66]. Complications of TIA
& stroke have been described in the treatment of varicose
veins [6], caused by emboli and macrobubbles [67],
although no reported cases have been described in treat-
ment of low-flow vascular malformations. A patent fora-
men ovale (PFO) is a relatively common occurrence in the
adult population with some suggesting 20 % [6]; however,
the vast majority are left to right shunts. Interestingly one
standard technique used to identify the presence of PFO’s
is the use of bubble-echo using agitated saline (foam) to
demonstrate and quantify the shunts [68].
can mimic the MRI findings, e.g. Ewings sarcoma (A). In a Ewings
sarcoma, the history is typically short and post-gadolinium images
demonstrate a more heterogeneous enhancement
Ethanol Ethanol can be used to treat malformations in a
direct (percutaneous) stick, transarterial or transvenous
administration. Injections should be performed very cau-
tiously; only after contrast injection has confirmed an ap-
propriate position within the malformation, due to the
significant complications that are associated [69].
Bleomycin In human tissue, it exhibits a dual effect in-
ducing DNA degradation in under-coiled strand regions
and has a specific sclerosing effect on endothelium [70]. It
is commonly used to treat Germ cell tumours and lym-
phomas [71, 72] and in 1977, Yura used Bleomycin to treat
cystic hygroma (macrocystic lymphatic malformations)
successfully [70]. Subsequently, other authors found suc-
cess with bleomycin for the treatment of both macrocystic
and microcystic lymphatic malformations [73–76]. In-
tralesional percutaneous injection of bleomycin was also
used in a number of different congenital vascular malfor-
mations including haemangiomas and low-flow venous
malformations with reports of significant improvement in
52 % and complete resolution in 32 % [50]. Muir pub-
lished his 5-year experience in over 160 patients in 2013
123

Fig. 11 Thrombosis can complicate venous malformations causing
swelling and pain. MRI T1-weighted sequences demonstrate high
signal intensity within the malformation consistent with haemorrhage
demonstrating success in a variety of congenital malfor-
mations [58].
Doxycycline Doxycycline can be administered by percu-
taneous injection of via a catheter. Depending on the size
of the lesion, treatment typically takes 3–6 sessions. It has
been shown to be a safe and affective sclerosant for treating
lymphatic malformations in children and has a wide safety
profile with significantly less neurotoxic effects and skin
necrosis compared to ethanol [77, 78]. It has also been
recommended for the use in abdominal lymphatic malfor-
mations where it appears to be safe in the peritoneal cavity
[79]. Its use has also been combined with STS 3 % with the
suggestion that a detergent sclerosant used first allows
better penetration of the doxycycline afterwards and better
results.
123
I. McCafferty: Management of Low-Flow Vascular Malformations…
(A arrowed) and demonstrate a low intensity filling defect with a high
signal intensity rim (B) which demonstrates enhancement post-
gadolinium injection (C, D)
OK432 (Picibanil) OK432 has a long history having first
been used clinically in 1967 and is typically used for the
treatment of macrocystic lymphatic malformations [80,
81]. It is injected into the lymphatic malformation ac-
cording to a method described by Ogita [82] with
0.1–0.2 mg of OK432 injected every 2 months for an ini-
tial 3 treatment sessions. Injection causes marked swelling
and sclerosis that does not spread outside the target lesion.
Sclerotherapy Procedure and Adjuvant Techniques
Pretreatment assessment is vital to assess which liquid
sclerosant agent to use. As previously discussed, MRI can
accurately identify the exact anatomical location of the
LFVM and can help predict complications. US has two
main roles to aid therapy; firstly to aid decision making by
 Table 5 Common agents used in the treatment of low flow vascular malformations
Name Mechanism of action Dosage Technique Uses Complications Notes

Sodium tetradecyl Anionic detergent based sclerosant. Endothelial 3 % commonest Typically LFVM’s Pain, skin staining, blistering, erosion, and Available in 0.2, 0.5, 1 and
sulphate—STS damage by decreasing the surface tension strength used administered as LFLM’s localised loss, transient nerve defects 3 %.
(Fibrovein STD resulting in thrombosis and fibrosis 0.5 mls/kg foam, using the (macrocystic) (commonly due to compression), Manufactured since 1966
Pharmaceutical, (maximum Tessari method as a haemoglobinuria and renal impairment (see (UK)
UK) single dose 1:2 or 1:3 (STS/air) Fig. 13)
mix Widely used in management
30 mls) [38] Potential rare of varicose veins
0.5–1 % used in Occasionally used as TIA and stroke (see text)
an emulsion with Wide safety margin
superficial VMs
lipiodol contrast Stability of foam relates
agent directly to the foam mix 1:3
Conscious sedation [ 1:2 etc
adequate for adults
with peripheral
lesions consider
GA for head and
neck
Ethanol Aggressive sclerosant causing instant precipitation 1 mg/kg total dose Patient require a GA LFVM’s Pain and swelling (significant at times resulting in Commonest agent used
(dehydrated of endothelial proteins, rapid thrombosis and Maximum single Injected neat using LFLM’s compartment syndrome), extensive tissue worldwide for LFVM’s
alcohol 100 % vessel occlusion session dose contrast washout (macrocystic) necrosis, permanent nerve injury, central Narrow safety margin
w/v—Sandoz Can cause trans-mural vessel necrosis and 60 mls never techniques nervous system depression, hypoglycaemia,
hypertension, haemolysis, pulmonary Ethanol levels correlate
Canada) diffusion into adjacent tissues causing exceeded More commonly directly with amount
significant non-target effects embolism, pulmonary vasospasm, cardiac
I. McCafferty: Management of Low-Flow Vascular Malformations…

Continuous mixed with contrast arrhythmias and death [124–128] injected [122, 123]
pulmonary (iodinated or
artery pressure lipiodol)
recording
advised
Only used by
experienced
operators
Bleomycin Is a cytotoxic anti-tumoral antibiotic discovered Constitute 15 mg Image guided LFLM’s Flu-like illness, pain and swelling, ulceration, In superficial lesions the dose
(Bleo-Kyowa; by Umezawa in 1966. Its cytotoxicity is of Bleomycin injections (microcystic) cellulitis can be diluted to 0.66 mg/
Kyowa Hakko mediated by DNA cleavage triggering single and powder with (ultrasound) LFLM’s Pulmonary fibrosis is a major complication ml
Kirin UK Ltd.) double strand breaks. Apoptosis occurs rapidly 15 mls of sterile Targeting matrix (macrocystic) related to cumulative dose. In dose range Routine lung function tests
in rapidly growing haemangiomas and immature saline—15 mg/ components and 50–150 mg 4 % incidence with zero mortality, prior to Bleomycin therapy
rapidly growing cells ml LFVM’s
spaces (matrix rich however 250–350 mg range 5 % incidence with (underlying pulmonary
Maximum single Conscious sedation or 2nd line) 0.9 % mortality disease may increase risks
dose 15 mg per adequate in adults of pulmonary fibrosis)
session
Under 1 year age
0.5–1 mg/kg
Record
cumulative
doses
Maximum doses
up to 100 mg
(clinician
decision)

123
 I. McCafferty: Management of Low-Flow Vascular Malformations…

other agents e.g. STS

defining the degree of cystic spaces and to assess ultra-

allergic to penicillin

reactions can occur

combination with
sound-guided accessibility, and second with agents that are

Beware in patients

as anaphylactic
Can be used in
Safe profile used as foam, ultrasound is used to assess treatment com-
pletion by identifying foam (microbubbles) within all
cystic spaces.
Notes

Pre-procedure Assessment Patients should be nil by

Haemolytic anaemia, hypoglycaemia

leukocytosis, thrombocytosis and

Post-injection flu-like illness with
mouth for 4 h for solids and 2 h for clear fluids. The ma-
prolonged swelling and skin

in neonates and neuropraxia

jority of patients with LFVM’s in the craniofacial area and

elevated C-reactive protein

approximately 10 % with

blistering the commonest

pyrexia, pain, swelling, in the pediatric population will have a GA; those in the
Complications occur in

periphery are typically treated with intravenous sedation.

All patients should have a cannula placed and an IVI
Complications

started to prevent dehydration. In patients with large le-

sions in whom renal complications may occur, an active
pre-hydration protocol should be used. Low molecular
weight heparin is used for 2 weeks prior to the procedure if
(macrocystic)

(macrocystic)

the VM is extensive and the patient has low fibrinogen

levels. This is to reduce the localised coagulopathy and
LFLM’s

LFLM’s

reduce the risk of treatment failure (Fig. 13).

Uses

Direct Stick Phlebography (DSP) Many operators advo-

needle or small
pigtail catheter

injection after
injections via

cate DSP in venous LFVM’s prior to installation of a liquid

Image guided

Image guided
adequate in

drainage of

component

sclerosant. Digital subtraction venography is performed via

Technique

Conscious
sedation

adults

cystic

a needle introduced into the lesion with US guidance and is

used to assess the morphology and venous drainage in a
dynamic manner (see Fig. 14). This is important in
1–2 KE (0.1–0.2 mg)

containing 1 9 108
session (10 mg/ml)
3–6 treatments often

OK432 measured in

assessing drainage into the deep veins. A number of clas-

1 KE has 0.1 mg of
100–1000 mg per

Klinische Einheit
every 2 months

sification systems have been described in the literature,

freeze dried
streptococci

cells [117]
(KE) units

which categorises venous LFVM’s, by their morphology

Dose range

required

and drainage characteristics; Goyal [69] and Fayad [83]

Dosage

described MRI classifications and Puig and Dubois [13, 84]

described a classification system (see Table 6) based on
activity of the Su strain and eliminates its toxin producing ability.
[129]. Exact mechanism is unclear but animal models demonstrate

Heating in the presence of penicillin at 370 increases antitumoural

sclerosant agent in lymphatic malformations in 1995 by Molitch

streptococcus pyogenes (Su strain) treated with benzylpenicillin.

drainage patterns seen on DSP. This system, which we use,

The cells remain intact but proliferative activity is lost [131]

correlates well with outcomes; types 1 and 2 have high

Is a tetracycline antibiotic originally reported as an effective

Is a lyophilized biological preparation containing cells of

success rates with type 4 having lower success rates (60 %

excluded) and higher complications.
a cellular reaction with deposition of fibrin [130]

Sclerotherapy Procedure The exact technique used de-

pends entirely on the nature of the underlying LFVM and
the operator’s preference.
In our institution, microcystic LM’s are treated pri-
marily with Bleomycin, in the manner previously de-
scribed, using a 25G spinal needle and US guidance to
Mechanism of action

ensure that bleomycin is instilled in the entire lesion in

equal aliquots. Doxycycline in used as a second line scle-
rosant. In macrocystic LM’s, a ‘‘2 needle’’ technique is
used (see Fig. 15), usually with a relatively large cannula,
e.g. 20G, placed with US so that the tips lie at opposite
Table 5 continued

ends of the lesion [4, 84]. This allows the sclerosant agent
Pharmaceutical

to either be installed via the dependent cannula until it

Co, Tokyo,
Doxycycline

(OK432)

exhausts from the non-dependent cannula or allow the

Picibanil

Japan)
(Chugai

agent to be washed ‘‘in and out’’ the LM on multiple oc-

Name

casions to allow greater sclerosant contact with the

123
I. McCafferty: Management of Low-Flow Vascular Malformations…
Fig. 12 Tessari technique for making foam sclerosant. Two leur lock syringes are connected via a three-way tap, with the tap turned so only the
two syringes are connected the plunger is depressed numerous times developing the white foam
endothelium. This technique significantly reduces the risk
of cyst rupture and extravasation of sclerosant, e.g. STS
which would lead to significant local complications. If this
is used as foam, then US is ideal to check that all cystic
spaces have been treated (microbubble US contrast); and if
not, further needle placements can be made and treated. If
Doxycycline is used, then the ‘‘2 needle technique’’ can be
used to install the treatment dose; however, some operators
have described using pigtail catheters (6–10F) to install
treatment doses, administered over 2–3 days, before re-
moving the pigtail. Other operators more recently have
suggested better results using an STS wash to ‘‘degrease’’
prior to administration of doxycycline or ethanol [85]. If
OK432 (Picibanil) is the agent of choice, this technique is
unnecessary and the agent is injected directly into the cysts
in divided doses with US guidance using 1–3KE dose.
In VM’s, there are a number of techniques, used de-
pendent on the Puig classification [84], to maximise scle-
rosant contact with the endothelium and cause fibrosis. If
the VM is type 1, then direct puncture with several small
gauge needles to cover the lesion ± DSP is sufficient prior
to installation of liquid sclerosant. Use of a tourniquet has
been recommended by a number of authors [54, 86–90] and
is used for a number of reasons. A tourniquet to 60 mmHg
will enhance the visualisation of the type 1 VM and allow
easier US-guided access; it also will control type 2/3 VM
lesion outflow veins to prevent loss of sclerosant and
therefore improve efficiency [62, 91–93]. Care should be
taken not to overfill VM’s under tourniquet control, and
needles should only be withdrawn once the tourniquet has
been released to prevent significant extravasation and local
complications. An ideal dwell time of sclerosant is between
2 and 10 min [84, 88, 94]. All liquid sclerosant agents are
radiolucent and therefore not visible on fluoroscopy. There
are a number of ways, however, to identify the sclerosant;
contrast can be added to facilitate visualisation; however,
this will lead to some sclerosant dilution and may reduce
effectiveness [95, 96]. Examples include iodinated contrast
with 3 % STS in a 1:2 or 1:3 ratio [88]; lipiodol with
ethanol in a 1:9 ratio [89] and 3 % STS with air and li-
piodol or iodinated contrast in a 2:1:1 or 3:1:1 ratio. Al-
ternatively if the VM has been opacified by contrast DSP,
then the use of road-mapping when administering scle-
rosant will allow visibility.
In our institution, our first line agent for treating VM’s is
3 % STS and we deliver this as a foam, using the Tessari
method [62], under US guidance, typically through 3-4
23G butterfly needles. DSP is performed to identify and
confirm intralesional placement and exclude any major
venous drainage and not to over distend the malformation.
Tourniquet control is not routinely used unless there is
significant venous outflow, which is seen on DSP, or when
the foam is injected under US control. If large draining
veins are identified that cannot be controlled by manual
compression or the use of a tourniquet, e.g. craniofacial
lesions then percutaneous administration of coils, glue,
direct ethanol injection (0.2–0.5 mls) or angioplasty bal-
loons accessed via jugular or femoral veins [4]. US and
fluoroscopy can be used to assess that foam sclerosant has
been administered to all parts of the VM (see Fig. 16), and
if need be introduce new needles to complete treatment. If
the VM involves overlying skin, then 0.5–1 % STS is used.
Post-procedure A compression bandage is applied in a
similar fashion to that used for the treatment of varicose
veins and is left on for 24 h [17]. Patients have analgesia
and steroids prescribed, and the intravenous fluids are
continued until adequate urine output is seen. The admin-
istration of non-steroidal anti-inflammatories is avoided in
the first 48 h in VM’s especially when using ethanol or 3 %
123
 I. McCafferty: Management of Low-Flow Vascular Malformations…

Fig. 13 Complications from

STS foam sclerotherapy occur.
Image A demonstrates the skin
changes that can occur if too
superficial injection is
performed which can include
necrosis. 3 months later, the
skin changes have significantly
improved although staining can
be permanent (B).
Haemoglobinuria is also
common after STS
sclerotherapy and can lead to
renal failure if not treated with
pre-hydration. The image shows
serial urine samples following a
significant (0.5 mls/kg–20 mls)
STS sclerotherapy (C)

STS, due to the potential risks of renal impairment sec-
ondary to haemoglobinuria. Although we do not routinely
use antibiotics orally or topically, some authors have rec-
ommended them when treating LM’s [4].
Follow-Up and Outcomes
Sclerotherapy frequently requires a course of treatment,
rather than a single session, to obtain satisfactory patient
symptom improvement; typically, this is between 3 and 5
sessions. Repeat treatments are ideally spaced between 6
and 8 weeks apart [88, 97, 98] and best arranged as a
course. At our institution, following a patient satisfaction
survey from 5 years of our malformation service, we found
that a more aggressive approach at the first session offered
the better satisfaction outcome, albeit with a slightly higher
initial minor complication rate, e.g. skin blistering (see
Fig. 17). There were no long-term complication sequelae.
This finding suggests that it is only at the first treatment
session that all the cystic spaces are likely to communicate,
thereby allowing sclerosant to freely fill all parts of the
lesion with the minimal number of needle insertions. Later
treatments were compromised by a degree of lesion com-
partmentalisation [10].
Patients should be given the details of a contact in the
vascular malformations service to whom to liaise with if
there are any immediate complications or issues. Patients
are then typically reviewed at their subsequent scle-
rotherapy treatment session or in outpatients if the
treatment course has been completed. Clinical review
should include lesion measurements, US evaluation and
clinical photography (see Fig. 18). If there has been little
symptomatic improvement and/or the lesion morphology
has changed, e.g. become more matrix rich, then con-
sideration should be given to changing the sclerosant
agent [10].

123
I. McCafferty: Management of Low-Flow Vascular Malformations…

Fig. 14 US-guided insertion of needles into the low-flow malforma- sclerosant to administer. Venography demonstrates a typical venous
tion is followed by direct stick venography to identify the venous malformation with no significant venous drainage into deep veins
morphology of the malformation to determine the amount of

outcome data. The choice of agent is therefore a personal

Table 6 Puig and Dubois classification of venous LFVM’s
decision dependent on experience. The development of
Type Description Sclerotherapy outcome agreed outcome measures and multicenter collaboration
Type 1 Isolated, well circumscribed Highest success rate
would greatly enhance the knowledge in this field and lead
lesion with negligible drainage to a better understanding of the correct sclerosant to use in
into a normal venous circulation specific circumstances and identify those lesions less likely
Type 2 Isolated, well circumscribed High success rate to respond to therapy.
lesion with drainage into VM’s have the greatest risk of progression in adoles-
a normal venous system
via normal veins
cence (70 %) with a smaller group progressing in child-
Type 3 Isolated, well circumscribed 50 % exclusion rate
hood (26 %). This is felt to represent hormonal influences
lesion with drainage as a factor for growth. In VM’s, clinical outcomes are
High complication
via and into dysplastic veins rates generally divided into arbitrary categories related to
Type 4 Lesion is composed of ectatic 60 % exclusion rate symptom improvement with MRI imaging size assessment.
and dysplastic veins Highest complication Ethanol and STS are the commonest sclerosant’s described
rate in the literature. Ethanol appears to have the highest suc-
cess rates quoted, up to 98 % with no recurrences within
There is no agreed follow-up in terms of imaging, 18 months [51, 99] but is a challenging agent to use due to
probably because treatment is solely based on symptomatic a relatively narrow safety window and high complication
improvement rather than changes in lesion morphology and rates [4, 99]. Ethanol has a higher minor and major com-
size improvement on MRI. Generally the interpretation of plication rate when compared to 3 % STS (12–30 vs.
symptom improvement is subjective, although a validated 0–10 %). STS also has high success rates 68–86 % [54,
quality of life questionnaire (QoL) would be extremely 88], and both ethanol and 3 % STS have high [75 % pa-
useful tool for assessment of treatments. MRI imaging tient satisfaction when used to treat facial VM’s [51, 52,
whilst informative to assess the lesion morphology changes 53]. Berenguer et al. [48, 98, 100] in 1999 described 75 %
and degree of fibrosis often does not correlate in a linear response rates with ethanol and STS sclerotherapy to VM’s
fashion with the patient’s symptom improvement or failure with no significant difference in outcomes related to mor-
[85]. However, a repeat MRI at 6/12 to assess response phology or location with only number of sessions and male
seems reasonable in appropriate cases [13]. sex being predictors of success. This is different to the
LFVM’s are rarely cured, and therefore, outcomes are Birmingham experience where layer involvement was
based on patient satisfaction and symptom improvement. significant in predicting outcomes.
There are no randomised control trials comparing surgery Mendonca et al. demonstrated response rates were lower
versus sclerotherapy versus conservative or with regards to in peripheral (limb) than craniofacial VM’s [8], and Kok
usage of different sclerosant agents and therefore no et al. demonstrated superficial lesions responded better than

123
 I. McCafferty: Management of Low-Flow Vascular Malformations…

Fig. 15 The technique of sclerotherapy depends to some degree the lymphatic malformation to act as an exhaust and prevent over
underlying type. In A, several needles are placed into the venous pressurising the system
malformation to access all areas; in B, larger needles are placed in a

Fig. 16 Sclerotherapy using foam can be monitored using ultrasound stick venography demonstrates the correct location for treatment and
where the foam (gas bubbles) can be visualised as a contrast media after foam sclerotherapy the air outlines the treated malformation (C,
with ultrasound and areas not treated can easily be seen (A, B). Direct D)

123
I. McCafferty: Management of Low-Flow Vascular Malformations…
Fig. 17 Immediate post-
treatment pictures demonstrate
the marked swelling of affected
areas with inflammatory
changes in the skin associated
with sclerotherapy (A, C).
Follow-up pictures show the
clinical improvement (B, D)
Fig. 18 Pictures pre and post-sclerotherapy to a venous malformation
deeper lesions. Markovic et al. [101] reviewed a 6-year
experience of foam STS sclerotherapy demonstrating a
92.9 % response rate with cellular microcystic morpho-
logical appearances having poor performance. It was sug-
gested that these lesions are more suitable for surgery;
however, Muir et al. [50, 58] have demonstrated excellent
results treating such lesions with bleomycin sclerotherapy.
Intramuscular VM’s often present with a mass and pain and
whilst traditionally treated with surgery have significant
morbidity after surgery. Sclerotherapy has high response
rates with upto 92 % of patient demonstrating improve-
ment [102] and surgery being reserved for sclerotherapy
failures of lesions that are focal and limited to a single
muscle. Yun et al. addressed predictors of response to
treatment with a review of 158 patients with a detailed
questionnaire. He found that the female sex, no draining
veins on venography (Puig type 1) and well-defined mar-
gins on MRI as positive predictors [103–106].
Sclerotherapy has also been shown to be highly suc-
cessful in higher risk areas. Stimpson et al. [107] described
83 % response rates for the trans-oral and percutaneous
access to treat oral and pharyngeal VM’s with no sig-
nificant complications. Due to the post-sclerotherapy,
swelling prophylactic tracheostomy must be considered for
laryngeal VM’s.
LM’s have the greatest risk of progression in adoles-
cence (63.8 %) although 40 % progress in childhood [16].
Spontaneous regression occurs in\2 %. Macrocystic LM’s
have a higher success rate than microcystic with effective
sclerotherapy treatment rates ranging from 88 to 100 %
and complication rates ranging from 2 to 22 %. Typically
complications are local and include skin loss, blistering,
nerve damage and scarring [77, 108, 109]. The results and
complications depend to a degree, on which sclerotherapy
agent is used. Ethanol due to its higher risk of nerve injury
123

and skin necrosis [4] is only useful for treating localised
small lesions. STS has been shown to be effective when
used alone or in combination with ethanol to treat macro-
cystic LM [103, 104, 110–113]; Kok et al. demonstrated
benefit rates of 84.3 % with the use of 3 % STS [114].
OK432 and Doxycycline treatments have been shown to
be a safe and effective treatment [77, 78, 108, 112, 115]
with similar success rates of 82–83 % with the OK432
patients requiring on average more treatment sessions 1.9
versus 1.0 (although overall treatment times were similar),
and had more post-operative swelling [31, 116, 117]. A
multicenter phase 2 trial comparing OK432 treatment with
conservative measures reported in 2009 demonstrated a
63 % complete and 94 % partial response rates to OK432
and \2 % spontaneous regression in the conservative
group [113]. Patient evaluation surveys have also con-
firmed anatomical location and morphology to be impor-
tant factors in predicting response with ethanol having the
highest complication rate [118].
Sclerotherapy has also been shown to be beneficial in
high-risk areas, e.g. orbital [119], pharyngeal/tracheal
[113] and abdominal lesions. Hill et al. [120] demonstrated
sclerotherapy with STS and ethanol for macrocystic LM’s
and doxycycline for microcystic LM’s safe and effective
results with drainage and treatment of orbital LMs. In ab-
dominal LM’s, doxycycline has been shown to be safe and
effective with low morbidity when treating abdominal LM
with mean doses of 608 mg/session and 1230 mg total
doses [103].
Microcystic LM’s present more of a treatment challenge
and multiple agents have been used with varying degrees of
success, and all studies report significantly lower response
rates in microcystic LM’s versus macrocystic LM’s [50,
58, 78, 118, 120, 121]. Bleomycin, however, seems to have
good patient tolerance with a good safety profile and is
demonstrating high success rates [50, 58, 107], and this
agent may become the agent of choice in these lesions.
Conclusion
The management of low-flow vascular malformations is
complex and requires a multidisciplinary approach. Treat-
ment should be aimed at those lesions that are symptomatic
or causing significant morbidity. Whilst surgery can be an
option in selective cases, direct stick sclerotherapy is a
preferred option as it is least invasive and can be repeated
on numerous occasions, this is particularly important in
venous malformations, which have a high recurrence rate.
A detailed knowledge of the sclerosing agents is extremely
important to personalise treatment plans depending on size
and morphology in adult and pediatric populations.
123
I. McCafferty: Management of Low-Flow Vascular Malformations…
Conflict of interest Author declare that they have no conflicts of
interest.
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