Slow-flow Vascular Malformations Research Articles

Outcome of bleomycin electrosclerotherapy of slow-flow malformations in adults and children.

To evaluate the safety and clinical outcome of bleomycin electrosclerotherapy (BEST) for treating extracranial slow-flow malformations. In this retrospective investigation of a multicenter cohort presenting symptomatic slow-flow malformations, patient records were analyzed with respect to procedural details and complications. A treatment-specific, patient-reported questionnaire was additionally evaluated, obtained 3-12 months after the last treatment, to assess the subjective outcomes, including mobility, aesthetic aspects, and pain, as well as the occurrence of postprocedural skin hyperpigmentation. All outcome parameters were compared according to patients' age. Overall, 325 BEST treatments were performed in 233 patients after intralesional and/or intravenous bleomycin injection. The total complication rate was 10.2% (33/325), including 29/352 (8.9%) major complications. Patient-reported mobility decreased in 10/133 (8.8%), was stable in 30/113 (26.5%), improved in 48/113 (42.5%), and was rated symptom-free in 25/113 (22.1%) patients. Aesthetic aspects were rated impaired compared to baseline in 19/113 (16.8%), stable in 21/133 (18.6%), improved in 62/113 (54.9%), and perfect in 11/133 (9.7%) patients. Postprocedural skin hyperpigmentation occurred in 78/113 (69%) patients, remaining unchanged in 24/78 (30.8%), reduced in 51/78 (65.5%), and completely resolved in 3/78 (3.8%) patients. The median VAS pain scale was 4.0 (0-10) preprocedural and 2.0 (0-9) postprocedural. Children/adolescents performed significantly better in all parameters compared to adults (≥ 16 years) (mobility, p = 0.011; aesthetic aspects, p < 0.001; pain, p < 0.001). BEST is effective for treating slow-flow vascular malformations, with few but potentially significant major complications. Regarding patient-reported outcomes, children seem to benefit better compared to older patients, suggesting that BEST should not be restricted to adults. Bleomycin electrosclerotherapy is a safe and effective approach and therapy should not be restricted to adults due to good clinical outcomes in children.

A Comprehensive Review of Sonographic Assessment of Peripheral Slow-Flow Vascular Malformations.

This comprehensive review explores the role of sonographic assessment in diagnosing and characterizing peripheral slow-flow vascular malformations (PSFVM). The review begins with an introduction providing the background and significance of PSFVM, defining these vascular anomalies, and emphasizing the importance of sonography in their diagnosis. The objectives focus on a thorough examination of existing literature, assessing the effectiveness of sonography in delineating morphological and hemodynamic features crucial for accurate classification. The summary of key findings highlights the diagnostic accuracy of sonography while acknowledging its limitations. Implications for clinical practice emphasize the practical utility of sonography in early diagnosis and preoperative planning, suggesting integration into multimodal approaches. The conclusion underscores the need for standardized criteria, ongoing education, and future research, positioning sonography as a valuable tool in the comprehensive management of PSFVM.

Preliminary results of the European multicentric phase III trial regarding sirolimus in slow-flow vascular malformations.

BACKGROUNDSlow-flow vascular malformations frequently harbor activating mutations in the PI3K/AKT/mTOR cascade. Phase II trials pinpointed sirolimus effectiveness as a drug therapy. Efficacy and safety of sirolimus thus need to be evaluated in large prospective phase III trials.METHODSThe Vascular Anomaly-Sirolimus-Europe (VASE) trial, initiated in 2016, is a large multicentric prospective phase III trial (EudraCT 2015-001703-32), which evaluates efficacy and safety of sirolimus for 2 years in pediatric and adult patients with symptomatic slow-flow vascular malformations. In this interim analysis, we studied all patients enrolled up to October 2021 who received sirolimus for 12 or more months or who prematurely stopped the treatment.RESULTSThirty-one pediatric and 101 adult patients were included in this analysis; 107 completed 12 or more months of sirolimus, including 61 who were treated for the whole 2-year period. Sirolimus resulted in a clinical improvement in 85% of patients. The efficacy appeared within the first month for the majority of them. Grade 3-4 adverse events were observed in 24 (18%) patients; all resolved after treatment interruption/arrest. Sirolimus increased feasibility of surgery or sclerotherapy in 20 (15%) patients initially deemed unsuitable for intervention. Among the 61 patients who completed the 2-year treatment, 33 (54%) reported a recurrence of symptoms after a median follow-up of 13 months after sirolimus arrest. While there was no difference in efficacy, clinical improvement was faster but subsided more rapidly in PIK3CA-mutated (n = 24) compared with TIE2-mutated (n = 19) patients.CONCLUSIONSirolimus has a high efficacy and good tolerance in treatment of slow-flow vascular malformations in children and adults.TRIAL REGISTRATIONClinicalTrials.gov NCT02638389 and EudraCT 2015-001703-32.FUNDINGThe Fonds de la Recherche Scientifique (FNRS grants T.0247.19, P.C005.22, T.0146.16, and P.C013.20), the Fund Generet managed by the King Baudouin Foundation (grant 2018-J1810250-211305), the Walloon Region through the FRFS-WELBIO strategic research programme (WELBIO-CR-2019C-06), the MSCA-ITN network V.A. Cure no. 814316, the Leducq Foundation Networks of Excellence Program grant "ReVAMP" (LFCR grant 21CVD03), the European Union's Horizon 2020 research and innovation programme under grant agreement no. 874708 (Theralymph), the Swiss National Science Foundation under the Sinergia project no. CRSII5_193694, and a Pierre M. fellowship.

A randomized, placebo-controlled study to evaluate safety and pharmacokinetics of ART-001 with a novel oral pediatric formulation in healthy subjects.

ART-001 is an orally available selective PI3Kα inhibitor currently being developed for the treatment of slow-flow vascular malformations (SFVMs). ART-001 used to be developed for advanced solid tumors, but was suspended largely due to significant pharmacokinetic (PK) variability in its phase I studies. This phase I, randomized, double-blinded, placebo-controlled study evaluated safety, tolerability and PK of ART-001 with a newly developed dry syrup formulation, which was designed to optimize PK properties of ART-001 and to be compliant with the pediatric population. Single and multiple doses of ART-001 were administered to healthy male adults. ART-001 was rapidly absorbed after the single and repeated doses, and the exposure of ART-001 increased with increased dose. The dry syrup formulation substantially improved the intersubject PK variability. Food decreased area under the concentration-time curve (AUC) and maximum plasma concentration by 12% and 36%, respectively. The plasma concentration had reached a steady-state on day 5 of the repeated doses of 100 mg and AUC accumulation ratio was 1.9. There were no deaths or serious adverse events. The most frequent adverse event was hyperglycemia. All cases of hyperglycemia were mild to moderate and transient, and required no medical interventions. Serum creatinine increase was observed in 300 mg once daily dosing group leading to dose discontinuation on day 5. In conclusion, it was demonstrated that the single doses and repeated doses of the ART-001 dry syrup formulation, at up to 400 and 100 mg, respectively, were safe and tolerated with favorable PK profile, supporting further clinical development for the treatment of SFVMs.

Fibroadipose vascular anomaly successfully treated with sirolimus: experience in 3 children

PurposeFibro-adipose vascular anomaly (FAVA) is a unique lesion composed of dense fibro-fatty tissue and slow-flow vascular malformations and is associated with somatic PIK3CA mutations. The patient usually presents with pain, swelling, functional restriction, and skin hyperesthesia. Therapeutic armamentarium includes cryoablation, sirolimus, and surgical debulking/excision. Sirolimus is highly effective for treatment of FAVA and is well tolerated. Here, we report our experience of treating FAVA with sirolimus in 3 patients.MethodsWe retrospectively reviewed data of 3 patients with FAVA who were treated with sirolimus at our institution.ResultsA total of 3 patients with FAVA being managed with sirolimus were assessed. Two out of 3 were male. The ages of the patients were 2, 12, and 17 years respectively. Sirolimus was started at a dose of 0.8 mg/m2/dose two times a day, and patients were treated for a mean of 10.6 months (range 10–11 months). Dose adjustments were made to keep trough serum levels between 5 and 12 ng/ml. All of them had reduction in pain, and 1 of them experienced it within 4 days of therapy initiation. Follow-up MRI revealed reduction in size in all 3 patients. Sirolimus was well tolerated with mild acne and dyslipidaemia being the only side effects observed.ConclusionSirolimus is quite an effective treatment for patients with FAVA and is well-tolerated without any major adverse effects. Given the rapid responses and a favourable safety profile, we believe that sirolimus can be considered for all patients with FAVA as a first-line therapy, but long-term follow-up data from well-designed clinical trials are required.

Pathophysiology of Slow-Flow Vascular Malformations: Current Understanding and Unanswered Questions.

Slow-flow vascular malformations include venous, lymphatic, and lymphaticovenous malformations. Recent studies have linked genetic variants hyperactivating either the PI3K/AKT/mTOR and/or RAS/RAF/MAPK signaling pathways with slow-flow vascular malformation development, leading to the use of pharmacotherapies such as sirolimus and alpelisib. It is important that clinicians understand basic and translational research advances in slow-flow vascular malformations. A literature review of basic science publications in slow-flow vascular malformations was performed on Pubmed, using search terms "venous malformation," "lymphatic malformation," "lymphaticovenous malformation," "genetic variant," "genetic mutation," "endothelial cells," and "animal model." Relevant publications were reviewed and summarized. The study of patient tissues and the use of primary pathogenic endothelial cells from vascular malformations shed light on their pathological behaviors, such as endothelial cell hyperproliferation and disruptions in vessel architecture. The use of xenograft and transgenic animal models confirmed the pathogenicity of genetic variants and allowed for preclinical testing of potential therapies. These discoveries underscore the importance of basic and translational research in understanding the pathophysiology of vascular malformations, which will allow for the development of improved biologically targeted treatments. Despite basic and translation advances, a cure for slow-flow vascular malformations remains elusive. Many questions remain unanswered, including how genotype variants result in phenotypes, and genotype-phenotype heterogeneity. Continued research into venous and lymphatic malformation pathobiology is critical in understanding the mechanisms by which genetic variants contribute to vascular malformation phenotypic features.

The development of flagellate hyperpigmentation after use of bleomycin for sclerotherapy slow flow vascular malformations

Introduction. Bleomycin is a cytotoxic antibiotic that is used as a sclerosing agent for sclerotherapy of vascular anomalies. Bleomycin is characterized by complications: nausea, vomiting, fever, the development of allergies/anaphylaxis, skin discoloration (hyperpigmentation), damage to lung tissue.Aim. To study the frequency of hyperpigmentation after administration of bleomycin for sclerotherapy of vascular malformations with slow flow characteristics. To present our own clinical observation of the development of skin hyperpigmentation after sclerotherapy of venous malformation with bleomycin.Materials and methods. A systematic review was conducted in foreign (PubMed, Web Of Science, Google Scholar, Scirus) and domestic databases (eLibrary) for the period from 2012 to 2022. As a result of the selection, 17 full-text articles remained suitable for their inclusion in the analysis.Results. In the first part of the review, 12 articles were analyzed, describing clinical observations of the development of “flaggelate” hyperpigmentation after chemotherapy of various neoplasms. In the second part of the review, an analysis of 4 articles describing clinical observations of the development of hyperpigmentation after intralesional administration of bleomycin into vascular malformation in 19 patients was carried out. Discussion. The occurrence of specific “flaggelate” hyperpigmentation after administration of bleomycin for sclerotherapy of vascular anomalies with slow flow characteristics is a rare complication. In the analysis carried out, there is no clear connection between the occurrence of hyperpigmentation and excess dosage.Conclusion. To prevent the appearance of hyperpigmentation, it is necessary to avoid excessive traumatization on time and immediately after sclerotherapy, including with ECG electrodes; avoid excessive oxygenation during the provision of anesthesia; it is necessary to avoid excessive insolation within 24–48 hours after sclerotherapy.

Clinical differences in sirolimus treatment with low target levels between children and adults with vascular malformations - A nationwide trial.

The clinical presentation of patients with slow-flow vascular malformations is very heterogeneous. High clinical burden and subsequent reduced health-related quality of life is something they have in common. There is an unmet medical need for these patients for whom regular treatments like surgery and embolization are either insufficient or technically impossible. Sirolimus has been reported to be effective and overall well-tolerated in most patients. However, the main limitation of sirolimus is the reported high toxicity, especially when target levels of 10-15 ng/mL are being used. We report the results of a phase IIB single-arm open-label clinical trial consisting of 68 (67 in the challenge phase and 68 in the rechallenge phase) evaluable patients (children n=33 and adults n=35) demonstrating that treatment with low sirolimus target levels (4-10ng/mL) is effective in 79.1% of the patients. When sirolimus treatment was stopped, the majority of patients experienced a recurrence of symptoms, supporting prolonged or even lifelong treatment requirement. Adults experienced a higher baseline pain score compared with children, having an estimated marginal mean of 6.2 versus 4.1, p < 0.05; however, they showed a similar decrease to children. Furthermore, the pediatric population experienced less often a sirolimus-related grade I-IV adverse event (35.9% vs. 64.1%, p > 0.05) compared with adults. Additionally, response rates were higher in children compared with adults (93.8% vs. 65.7%, p < 0.05), and children responded faster (28 vs. 91 days, p < 0.05). These results suggest benefits of sirolimus in patients with slow-flow vascular malformations and support its initiation as young as possible.

A rare case of orbital and diffuse conjunctival venous malformation

Cavernous hemangiomas (CH) are slow-flow venous malformations (VMs), not true vascular tumors. Although these are the most common benign orbital tumors in adults, conjunctival VMs are a rarity and account for less than 1% of all conjunctival tumors. We herein report a case of a 25-year-old male patient who presented with a large violaceous mass involving the inferior bulbar conjunctiva that had been present for 10 years. It was painless, progressive, and gradually increased in size over 10 years, and was associated with occasional bleeding. Any syndromic association was ruled out. Contrast-enhanced magnetic resonance imaging (CEMRI) revealed the presence of slow-flow vascular malformations involving the right superior and inferior eyelids with intraconal and extraconal involvement. An incision biopsy and histopathology (H/P) confirmed the diagnosis of formerly-called cavernous hemangioma (slow-flow VMs). The conjunctival mass was further managed by surgical debulking with ocular surface reconstruction, whereas the intraorbital part was kept under observation owing to its small size. The postoperative period was uneventful.

Vascular endothelial growth factor, tissue factor, coagulation and fibrinolysis markers in slow-flow vascular malformations: a prospective study of treatment with sirolimus.

Slow-flow vascular malformations (VMs), especially those with venous components, can be complicated by localized intravascular coagulopathy (LIC), responsible for pain and impaired quality of life. Several studies have shown the effectiveness of mTOR inhibitors (especially sirolimus) on slow-flow VMs but its effect on coagulation has been poorly studied, especially in children. Our study shows that venous and combined VMs are associated with coagulation abnormalities and provides novel evidence that sirolimus improves coagulopathy in venous malformations. However we did not clearly evidence predictive biomarkers of response to sirolimus but this is the first study attempting to highlight predictive markers of response to sirolimus.

Clinical Emergence of Low-flow Vascular Malformations After Vaccination Against SARS-CoV-2: A Case Series

Studies have demonstrated that all 3 of the FDA-approved COVID-19 vaccines (Pfizer-BioNTech, Moderna, and Johnson &amp; Johnson) are effective at reducing SARS-CoV-2-related hospitalizations, severe disease, and death. While these vaccinations have demonstrated a compelling safety profile, no discussion regarding the impact of COVID-19 vaccination on the exacerbation of slow-flow vascular malformations (SFVMs) has been had. We present the first case series of 3 consecutive patients who demonstrated clinical emergence or exacerbation of venous malformation status-post COVID-19 vaccination. As trauma, infection, and systemic inflammation can contribute to exacerbation of these vascular anomalies, COVID-19 vaccination may contribute to the clinical emergence and exacerbation of vascular malformations in patients with initial subclinical presentation.

Comprehensive targeted next-generation sequencing in patients with slow-flow vascular malformations.

Recent studies have shown that the PI3K signaling pathway plays an important role in the pathogenesis of slow-flow vascular malformations (SFVMs). Analysis of genetic mutations has advanced our understanding of the mechanisms involved in SFVM pathogenesis and may identify new therapeutic targets. We screened for somatic variants in a cohort of patients with SFVMs using targeted next-generation sequencing. Targeted next-generation sequencing of 29 candidate genes associated with vascular anomalies or with the PI3K signaling pathway was performed on affected tissues from patients with SFVMs. Fifty-nine patients with SFVMs (venous malformations n = 21, lymphatic malformations n = 27, lymphatic venous malformations n = 1, and Klippel-Trenaunay syndrome n = 10) were included in the study. TEK and PIK3CA were the most commonly mutated genes in the study. We detected eight TEK pathogenic variants in 10 samples (16.9%) and three PIK3CA pathogenic variants in 28 samples (47.5%). In total, 37 of 59 patients (62.7%) with SFVMs harbored pathogenic variants in these three genes involved in the PI3K signaling pathway. Inhibitors of this pathway may prove useful as molecular targeted therapies for SFVMs.

Comparison of polidocanol foam versus bleomycin polidocanol foam for treatment of venous malformations

ObjectiveThe objective of this research was to retrospectively investigate the difference of safety and efficacy between polidocanol foam and bleomycin polidocanol foam (BPF) in the treatment of venous malformations (VMs), and provide clinical evidence for the application of BPF for VMs. MethodsPatients with VMs treated with polidocanol foam and BPF were included between July 2018 and July 2020. The VM tissue involvements and symptoms were collected. The treatment outcomes were evaluated by the clinical improvement of symptoms and the degree of devascularization on ultrasound examination or magnetic resonance imaging. Patients were followed up for 1, 3, and 6 months after the sclerotherapy. Immediate and delayed complications were closely followed and recorded. ResultsA total of 51 patients were included, including 34 females and 17 males with a mean age of 26.8 years (range, 5-65 years). The most commonly involved sites were lower extremities (31/60 [51.7%]) and the most common symptom was pain (33/51 [64.7%]). Fifty-four sclerotherapies were performed with a mean of 1.06 ± 0.24 sessions (range, 1-2 sessions) per patient. The reduction percentage of lesion volume in the BPF group was significantly higher than the polidocanol foam group (79.4 ± 1.6% vs 55.7 ± 6.1%; P < .001). Patient satisfaction scores in the BPF group were significantly higher than the polidocanol foam group (7.2 ± 1.1 vs 5.7 ± 0.8; P < .001). No major complication was observed in either group. Cardiovascular and Interventional Radiological Society of Europe (CIRSE) grade 1 complications occurred in 5 of 21 patients in the BPF group and 7 of 30 patients in the polidocanol foam group, CIRSE grade 2 complications occurred in 5 of 21 patients in the BPF group and 4 of 30 patients in the polidocanol foam group; there were no significant differences between the two groups. ConclusionsBPF is a safe and effective sclerosant for VMs, showing better efficacy and similar safety as commonly used mild sclerosants. It could be a promising agent to treat VMs or other slow-flow vascular malformations.

Lymphatic-Venous Malformation Presenting as a Mediastinal Mass in a 6-Year-Old Boy

Among the slow-flow vascular malformations in children, lymphatic malformation (LM; formerly known as lymphangioma) typically develops in the neck (75‒90%), with the posterior triangle being the most commonly affected site (1,2). Ninety percent of the entity is detected in children younger than 2 years (2). LM tends to behave like lymphatic-venous malformation (LVM; formerly, lymphangiohemangioma), but these two entities are clinically indistinguishable (3,4). This article describes a rare case of LVM, presenting as a new-onset, cervical mass extending to the mediastinum in a school-aged boy, that is, an unusual location and age for the malformation.

A Large Fetal Venous Malformation

A 28-year-old woman was referred to our institution at 35 weeks after an ultrasound diagnosis of an oral fetal lesion. Magnetic resonance showed a mass originating from the anterior part of the tongue with some areas of internal heterogeneity, possibly representing vascular structures. The multidisciplinary team decided to perform a cesarean delivery at 38 weeks. A large, well-defined bluish/purple exophytic mass arising from the apex of the tongue was confirmed right after birth, and a vascular anomaly was suspected. Precocious complete surgical excision and oral motor rehabilitation and feeding were performed. According to the 2018 International Society for the Study of Vascular Anomalies Classification (ISSVA), histological analysis confirmed a venous vascular malformation. Although rare, venous malformations represent the most common type of congenital vascular malformation. They are considered simple and slow-flow vascular malformations. Airway compromise may be a major concern when aerodigestive system involvement is present. Anatomic deformities and their functional and psychosocial impact are also important concerns. Herein, prompt recognition of an oral fetal mass allowed cautious delivery and postnatal management. It highlights the importance of careful prenatal diagnosis in managing potentially life-threatening congenital malformations.

Diagnostic Accuracy of SWAN in the Diagnosis of Low-Flow Brain Vascular Malformations in Childhood

Abstract Purpose The main objective of this study is to demonstrate the diagnostic accuracy of susceptibility-weighted angiography (SWAN) in the diagnosis of slow-flow cerebral vascular malformations, especially developmental venous anomaly (DVA). We also aimed to determine the prevalence of DVAs identified by SWAN at 1.5 T. Methods We retrospectively evaluated 1,760 axial SWAN images for the diagnosis of low-flow vascular anomaly. Among them were 305 patients who underwent contrast-enhanced examination due to different indications. Postcontrast images were analyzed by different radiologists who were blinded to patients. The presence of DVA and other features such as location, length, depth, and direction of drainage vein was evaluated. Results Twenty-six patients with DVA had both SWAN and postcontrast images. There were four false-negative patients with SWAN. The sensitivity of the SWAN sequence was 84.6%. In addition, totally 77 DVA (4.36%), 2 capillary telangiectasia (0.11%), and 2 cavernous malformations (0.11%) were detected in 1,760 patients. Conclusion SWAN is an effective method for the diagnosis of developmental venous anomalies and other low-flow cerebral vascular malformations. Especially in the pediatric age, susceptibility-weighted imaging sequences are useful to limit contrast use.

Sirolimus (Rapamycin) for Slow-Flow Malformations in Children

Sirolimus is increasingly being used to treat various vascular anomalies, although evidence of its efficacy is lacking. To assess the efficacy and safety of sirolimus for children with slow-flow vascular malformations to better delineate the indications for treatment. This multicenter, open-label, observational-phase randomized clinical trial included 59 children aged 6 to 18 years with a slow-flow vascular malformation who were recruited between September 28, 2015, and March 22, 2018, in 11 French tertiary hospital centers. Statistical analysis was performed on an intent-to-treat basis from December 4, 2019, to November 10, 2020. Patients underwent an observational period, then switched to an interventional period when they received oral sirolimus (target serum levels, 4-12 ng/mL). The switch time was randomized from month 4 to month 8, and the whole study period lasted 12 months for each patient. The primary outcome was change in the volume of vascular malformations detected on magnetic resonance imaging scan (with centralized interpretation) per unit of time (ie, between the interventional period and the observational period). Secondary outcomes included subjective end points: pain, bleeding, oozing, quality of life, and safety. Among the participants (35 girls [59.3%]; mean [SD] age, 11.6 [3.8] years), 22 (37.3%) had a pure venous malformation, 18 (30.5%) had a cystic lymphatic malformation, and 19 (32.2%) had a combined malformation, including syndromic forms. Variations in the volume of vascular malformations detected on magnetic resonance imaging scans associated with the duration period were not overall significantly different between the interventional period and the observational period (all vascular malformations: mean [SD] difference, -0.001 [0.007]; venous malformations: mean [SD] difference, 0.001 [0.004]; combined malformations: mean [SD] difference, 0.001 [0.009]). However, a significant decrease in volume was observed for children with pure lymphatic malformations (mean [SD] difference, -0.005 [0.005]). Overall, sirolimus had positive effects on pain, especially for combined malformations, and on bleeding, oozing, self-assessed efficacy, and quality of life. During sirolimus treatment, 56 patients experienced 231 adverse events (5 serious adverse events, none life-threatening). The most frequent adverse event was an oral ulcer (29 patients [49.2%]). This observational-phase randomized clinical trial allows for clarifying the goals of patients and families when starting sirolimus therapy for children older than 6 years. Pure lymphatic malformations seem to be the best indication for sirolimus therapy because evidence of decreasing lymphatic malformation volume per unit of time, oozing, and bleeding and increasing quality of life was found. In combined malformations, sirolimus significantly reduced pain, oozing, and bleeding. Benefits seemed lower for pure venous malformations than for the 2 other subgroups, also based on symptoms. ClinicalTrials.gov Identifier: NCT02509468; clinicaltrialsregister.eu Identifier: 2015-001096-43.

Retrospective Study of Hematologic Complications in Vascular Malformation Patients with Localized Intravascular Coagulopathy Undergoing Surgical Intervention

BACKGROUNDSlow-flow vascular malformations such as multifocal or extensive venous (VM), venous-lymphatic (VLM), capillary-venous (CVM) and capillary-lymphatic-venous malformations (CLVM), are commonly associated with spontaneous thrombosis and thrombolysis, a phenomenon termed localized intravascular coagulopathy (LIC). LIC is characterized by elevated D-dimer, low fibrinogen, and/or mild thrombocytopenia and may progress to disseminated intravascular coagulopathy. Individuals with LIC are at an increased risk for hematological complications, particularly when undergoing surgical procedures on or near the vascular malformation. The pathogenesis of this coagulopathy is unknown but thought to be secondary to slow blood flow, consumption of coagulation factors, abnormal endothelium and loss of protective anticoagulant factors. The exact mechanism of dysregulation of the coagulation pathway and the resultant hematologic complications remains largely unstudied. Furthermore, many institutions are empirically using peri-procedural LMWH in attempt to decrease morbidity in individuals with LIC despite supportive evidence. This work will be the largest retrospective study investigating post-procedural hematologic complications in children and young adults with vascular malformations as only case reports and series have been published to date. METHODRetrospective chart review was conducted of medical records of adult and pediatric patients with slow-flow vascular malformations with LIC who underwent a surgical intervention and/or sclerotherapy procedure at Cincinnati Children's Hospital Medical Center from 7/1/2008 to 12/31/2016. LIC was defined by high D-dimer (5 times upper limit of normal), fibrinogen <150mg/dL and/or platelet count <150K/mcL. Hematologic complications included any clinically relevant bleeding or clotting abnormality that occurred intra-operatively, 2 weeks post-procedure and/or while on LMWH prophylaxis, up to 2 weeks, prior to surgery. Use of LMWH including dose, frequency and course length was evaluated. RESULTSThirty-nine patients with slow-flow vascular malformations with associated LIC (24 with extensive VM/VLM, 9 with multiple VM/VLM, 4 with CLVM, 2 with localized VM/VLM) underwent a total of 236 sclerotherapy procedures with 86% occurring in individuals under 18 years of age. At our institution, LMWH was administered at 0.5mg/kg/dose once daily for 2 weeks before and after sclerotherapy in 87% of sclerotherapy cases. No thrombotic complications occurred in children. One adult patient on LMWH at treatment dosing developed pulmonary emboli (PE), presumably from deep vein thrombosis (DVT) of the treated extremity; the patient was a known smoker with a history of DVT/PE. In 5 patients fibrinogen levels dropped below 100 mg/dL post-sclerotherapy for which cryoprecipitate was administered and no bleeding complications occurred. No intra-op bleeding or thrombotic events occurred.Total of 104 patients with slow flow malformations underwent 265 procedures represented by all major surgical subspecialties, excluding sclerotherapy. Twenty-seven (26%) of these patients had evidence of LIC prior to surgery. Eight significant bleeding episodes and 3 thrombotic events occurred; seven (64%) of which occurred in patients with known LIC. Two patients had both a clotting and hemorrhagic event. Although complications occurred similarly in both children and adults, 100% of the hematogic complications occurred in patients with extensive combined vascular malformations , most with venous ectasias. The dosing, course length and frequency of LMWH use was highly variable among patients undergoing surgery. CONCLUSIONSProphylactic LMWH use was common in this patient population and did not appear to increase the risk of significant bleeding before, during or after sclerotherapy. Thrombotic events after sclerotherapy appear rare but may still occur. In patients with known LIC, attempts to correct coagulation abnormalities should be made prior to undergoing major surgical interventions. Further studies evaluating peri-procedural LMWH are needed to determine benefit and optimal dosing. Collaborative plans exist to combine data with Boston Children's Hospital so that future studies will allow for comparative effectiveness analysis of LMWH use at different doses in this patient population. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Giant venous malformation of the tongue with macroglossia: A hidden menace

Venous malformations (VMs) are congenital slow flow vascular malformations that are usually present at birth. They grow proportionate with the age and do not regress with time differentiating them from hemangiomas. VM presents as bluish discoloration of skin/mucosa or as soft subcutaneous masses. It may affect any organ, including viscera-like gastrointestinal tract or brain. VM is generally slowly progressive and asymptomatic as they grow slowly with age. We report the case of asymptomatic giant VM over the tongue for which the patient presented due to herpetic stomatitis.

Ultrasound Evaluation of Pediatric Slow-Flow Vascular Malformations: Practical Diagnostic Reporting to Guide Interventional Management.

OBJECTIVE. This article reviews the ultrasound characteristics of pediatric slow-flow vascular malformations and underscores findings that significantly impact diagnosis and treatment. Key imaging features are discussed including lesion size, malformation location, morphology, and mimics. CONCLUSION. Ultrasound findings affect the management of slow-flow vascular malformations and should be emphasized in lesion diagnosis. Superficial, focal lesions with well-defined margins are ideal for ultrasound evaluation.