Retrospective study of hematologic complications in patients with slow-flow vascular malformations undergoing sclerotherapy.

BACKGROUND: Slow-flow vascular malformations (SFVM) are associated with localized intravascular coagulopathy (LIC), which is characterized by elevated D-dimer and, when severe, hypofibrinogenemia. LIC results in intralesional clotting and hemorrhage and increases risk for significant thrombotic and bleeding complications. Sclerotherapy has been a suggested potential trigger for LIC worsening to disseminated intravascular coagulopathy. Hematologic complications of sclerotherapy in SFVM, along with low-molecular-weight heparin (LMWH) used to prevent worsening LIC, are largely unstudied. PROCEDURE: Medical records of patients with SFVM and LIC who underwent sclerotherapy at Cincinnati Children's Hospital Medical Center from July 2008 to December 2016 were reviewed for periprocedural hematologic complications. LMWH dose, frequency, and course length were evaluated. RESULTS: Fifty-nine patients with SFVM and LIC underwent 281 sclerotherapy procedures, of which 86% were in children. Eighty-five percent of patients received periprocedural LMWH, although at various doses and course lengths. No thrombotic complications occurred in children. One adult on LMWH developed pulmonary emboli after sclerotherapy. No major bleeding complications occurred postoperatively. In four patients, fibrinogen dropped below 100 mg/dL post-sclerotherapy, requiring cryoprecipitate. One patient required packed red blood cell (RBC) transfusion for sclerotherapy-induced hemolysis. No intraoperative bleeding or thrombotic events occurred. CONCLUSION: LMWH use, at subtherapeutic dosing, was common in this patient population and did not appear to increase risk of significant bleeding before, during, or after sclerotherapy. In children with SFVM, bleeding and thrombotic complications after sclerotherapy appear rare. Although safe, prospective studies are needed to evaluate the efficacy of LMWH to prevent worsening coagulopathy with procedures.

Propranolol versus steroids for the treatment of ulcerated infantile hemangiomas.

BACKGROUND: There has been a paradigm shift from steroids to propranolol for the pharmacologic treatment of infantile hemangiomas (IH); however, the outcomes for ulcerated IH are not well studied. The purpose of this study was to compare the efficacy of steroids and propranolol specifically for ulcerated IH. METHODS: A retrospective review was conducted on patients with ulcerated IH treated with propranolol or steroids at a single tertiary care institution between 2007 and 2014. Patient characteristics, hemangioma features, and outcomes, including time to heal and medication complications, were compared between propranolol and steroid patients. RESULTS: There were 29 patients treated with propranolol and 23 with steroids. There were no significant differences in the two treatment groups including age, race, sex, size, or insurance status. There were more head/neck IH in the steroid group. There was no significant difference in the percentage of healed lesions (93 vs. 74%, P = 0.12) or the median time to heal (80 vs. 126 days, p = 0.21) between groups. Overall complication rates also did not vary between medications (24 vs. 44%, P = 0.14). CONCLUSION: Propranolol is noninferior to steroids for the treatment of ulcerated IH; however, healing time is lengthy regardless of treatment. While side effect profiles differed between medications, the overall complication rate was similar.

Response of Blue Rubber Bleb Nevus Syndrome to Sirolimus Treatment.

BACKGROUND: Blue rubber bleb nevus syndrome (BRBNS) is a rare multifocal venous malformation syndrome involving predominantly the skin and gastrointestinal tract. Traditional treatment modalities include corticosteroids, interferon-α, sclerotherapy, and aggressive surgical resection. Sirolimus has been used in several single case reports. PROCEDURE: We performed a single-institution retrospective review of four children with BRBNS, who received sirolimus as part of their treatment regimens. A diagnosis of BRBNS was based on clinical, radiologic, and pathologic criteria. RESULTS: Median age was 6.5 years (range: 2-16 years). Pathologic evaluations revealed a combined malformation with venous and lymphatic components. The novel finding of a lymphatic component was confirmed with PROX-1 immunostaining. Patients received oral sirolimus with target drug levels between 10 and 13 ng/ml. Responses to treatment were defined as stabilization/decrease in size of lesions; resolution of transfusion requirements; reduction in pain, and improvement in quality of life (QOL). Median time to response was 1.5 months (SD ± 0.96 month, range: 1-3 months). Median follow-up was 21 months (range: 18-26 months). Lesion size and characteristics improved in all patients. All patients reported decrease in pain and improvement in QOL. All three patients requiring transfusions became transfusion-independent. One patient had resolution of coagulopathy. Adverse effects of sirolimus consisted of mucositis in three patients and neutropenia in one patient. CONCLUSIONS: Sirolimus is safe and efficient for the treatment of BRBNS. Further prospective studies are needed to evaluate the long-term effectiveness of this drug. This is the first report that identifies a lymphatic component as part of BRBNS.

Rebound Growth of Infantile Hemangiomas After Propranolol Therapy.

BACKGROUND AND OBJECTIVES: Propranolol is first-line therapy for problematic infantile hemangiomas (IHs). Rebound growth after propranolol discontinuation is noted in 19% to 25% of patients. Predictive factors for rebound are not completely understood and may alter the management approach. The goal of the study was to describe a cohort of patients with IHs treated with propranolol and to identify predictors for rebound growth. METHODS: A multicenter retrospective cohort study was conducted in patients with IHs treated with propranolol. Patient demographic characteristics, IH characteristics, and specifics of propranolol therapy were obtained. Episodes of rebound growth were recorded. Patients' responses to propranolol were evaluated through a visual analog scale. RESULTS: A total of 997 patients were enrolled. The incidence of rebound growth was 231 of 912 patients (25.3%). Mean age at initial rebound was 17.1 months. The odds of rebound among those who discontinued therapy at <9 months was 2.4 (odds ratio [OR]: 2.4; 95% confidence interval [CI]: 1.3 to 4.5; P = .004) compared with those who discontinued therapy between 12 to 15 months of life. Female gender, location on head and neck, segmental pattern, and deep or mixed skin involvement were associated with rebound on univariate analysis. With multivariate analysis, only deep IHs (OR: 3.3; 95% CI: 1.9 to 6.0; P < .001) and female gender (OR: 1.7; 95% CI: 1.1 to 2.6; P = .03) were associated. Of those with rebound growth, 83% required therapeutic modification including 62% of patients with modifications in their propranolol therapy. CONCLUSIONS: Rebound growth occurred in 25% of patients, requiring modification of systemic therapy in 15%. Predictive factors for rebound growth included age of discontinuation, deep IH component, and female gender. Patients with these predictive factors may require a prolonged course of therapy.

Efficacy and Safety of Sirolimus in the Treatment of Complicated Vascular Anomalies.

BACKGROUND AND OBJECTIVES: Complicated vascular anomalies have limited therapeutic options and cause significant morbidity and mortality. This Phase II trial enrolled patients with complicated vascular anomalies to determine the efficacy and safety of treatment with sirolimus for 12 courses; each course was defined as 28 days. METHODS: Treatment consisted of a continuous dosing schedule of oral sirolimus starting at 0.8 mg/m(2) per dose twice daily, with pharmacokinetic-guided target serum trough levels of 10 to 15 ng/mL. The primary outcomes were responsiveness to sirolimus by the end of course 6 (evaluated according to functional impairment score, quality of life, and radiologic assessment) and the incidence of toxicities and/or infection-related deaths. RESULTS: Sixty-one patients were enrolled; 57 patients were evaluable for efficacy at the end of course 6, and 53 were evaluable at the end of course 12. No patient had a complete response at the end of course 6 or 12 as anticipated. At the end of course 6, a total of 47 patients had a partial response, 3 patients had stable disease, and 7 patients had progressive disease. Two patients were taken off of study medicine secondary to persistent adverse effects. Grade 3 and higher toxicities attributable to sirolimus included blood/bone marrow toxicity in 27% of patients, gastrointestinal toxicity in 3%, and metabolic/laboratory toxicity in 3%. No toxicity-related deaths occurred. CONCLUSIONS: Sirolimus was efficacious and well tolerated in these study patients with complicated vascular anomalies. Clinical activity was reported in the majority of the disorders.

Perioperative care of the vascular anomaly patient.

Patients with vascular anomalies present specific and unique challenges to providers of their postoperative care. Vascular anomalies can range from localized solitary lesions to diffuse lesions with vessel malformations and associated soft tissue, muscle, organ, and bone involvement. Perioperative issues for these patients can be complicated and include coagulopathies requiring anticoagulation, the need for postoperative surgical drains and specialized wound care, and the use of compression garments to maintain the desired postoperative result. This article will address these specific concerns for patients with vascular anomalies in order to create a framework for consistent and appropriate perioperative care.