Faculty Bibliography

Infantile hemangiomas (IHs) are common neoplasms composed of proliferating endothelial-like cells. Despite the relative frequency of IH and the potential severity of complications, there are currently no uniform guidelines for treatment. Although propranolol has rapidly been adopted, there is significant uncertainty and divergence of opinion regarding safety monitoring, dose escalation, and its use in PHACE syndrome (PHACE = posterior fossa, hemangioma, arterial lesions, cardiac abnormalities, eye abnormalities; a cutaneous neurovascular syndrome characterized by large, segmental hemangiomas of the head and neck along with congenital anomalies of the brain, heart, eyes and/or chest wall). A consensus conference was held on December 9, 2011. The multidisciplinary team reviewed existing data on the pharmacologic properties of propranolol and all published reports pertaining to the use of propranolol in pediatric patients. Workgroups were assigned specific topics to propose protocols on the following subjects: contraindications, special populations, pretreatment evaluation, dose escalation, and monitoring. Consensus protocols were recorded during the meeting and refined after the meeting. When appropriate, protocol clarifications and revision were made and agreed upon by the group via teleconference. Because of the absence of high-quality clinical research data, evidence-based recommendations are not possible at present. However, the team agreed on a number of recommendations that arose from a review of existing evidence, including when to treat complicated IH; contraindications and pretreatment evaluation protocols; propranolol use in PHACE syndrome; formulation, target dose, and frequency of propranolol; initiation of propranolol in infants; cardiovascular monitoring; ongoing monitoring; and prevention of hypoglycemia. Where there was considerable controversy, the more conservative approach was selected. We acknowledge that the recommendations are conservative in nature and anticipate that they will be revised as more data are made available.

Infantile hemangiomas (IH) are benign tumors of endothelial-like cells. Occurring in 4.5% of children, they are the most common tumor of childhood. The great majority of patients with IH will not need treatment, but 10% require systemic treatment. Many treatments have been described for the treatment of IH, but the Food and Drug Administration has not approved any. Over the last decade, numerous reports of successful treatment of IH with propranolol have been published. Despite its widespread use, little is known regarding the proper dosing, safety monitoring, and during of treatment or long-term outcomes for propranolol treatment of IH. Given its potential side effects, detailed education regarding proper administration of the medication as well as warning signs to watch for is necessary for parents and caretakers. Herein, we provide a parental handout that practitioners can individually tailor for use in their clinics when educating parents and caretakers about the use of propranolol for IH. Updates will also need to be made as more is learned regarding the optimal dosing and safety monitoring when using propranolol for this indication.

The term "vascular anomalies" embraces a spectrum of medical conditions characterized by abnormal growth or development of blood and/or lymphatic vessels. Patient management is frequently provided in a multidisciplinary team approach, as there are many facets to evaluation and treatment. Clinical and basic research during the past decade has enhanced our knowledge, providing insight into possible etiologies, associated genetic mutations, cellular mechanisms modulating the development, and natural history of these disorders. Concomitantly, new therapeutic agents have been identified, which has transformed patient management. In this review, a brief overview of the field including an update in basic research is presented, followed by a discussion of current therapies and their purported mechanism of action.

Propranolol is a non-selective beta-adrenergic antagonist successfully used in a case of kaposiform hemangioendothelioma (KHE) associated with Kasabach-Merritt phenomenon (KMP). We report 11 patients treated with propranolol for KHE and the related variant tufted angioma (TA), six of whom also had KMP. The varied responses to treatment, with only 36% responding in our series, demonstrate the need for further study of this medication before routine use for these indications.

PHACE syndrome (OMIM #606519) is a neurocutaneous syndrome of unknown etiology and pathogenesis. We report on an individual with PHACE syndrome with a complete deletion of SLC35B4 on 7q33. In order to further analyze this region, SLC35B4 was sequenced for 33 individuals with PHACE syndrome and one parental set. Common polymorphisms with a possible haplotype but no disease causing mutation were identified. Sixteen of 33 samples of the PHACE syndrome patients were also analyzed for copy number variations using high-resolution oligo-comparative genomic hybridization (CGH) microarray. A second individual in this cohort had a 26.5 kb deletion approximately 80 kb upstream of SLC35B4 with partial deletion of the AKR1B1 on 7q33. The deletions observed on 7q33 are not likely the singular cause of PHACE syndrome; however, it is possible that this region provides a genetic susceptibility to phenotypic expression with other confounding genetic or environmental factors.

Object Surgery is increasingly used to treat children with refractory epilepsy. Before surgery, the authors routinely evaluated the coagulation profile to identify coagulation abnormalities not established by personal and family history, physical examination, and routine screening tests. Methods Thirty-nine consecutive children undergoing testing prior to epilepsy surgery were prospectively evaluated. The authors evaluated a detailed hematological history and an elaborative hematological panel including complete blood count, hepatic panel, anticoagulant levels, coagulation profile (prothrombin time, partial thromboplastin time, international normalized ratio, fibrinogen, thrombin time, von Willebrand antigen, ristocetin cofactor, factor VIII, and individual factor assays when indicated) and platelet aggregation studies (in the presence of adenosine diphosphate, epinephrine, collagen, and ristocetin). Patient variables included tuberous sclerosis complex (TSC), age at epilepsy onset, age at surgery, seizure frequency, number and type of antiepileptic drugs, recent or present ketogenic diet, and use of selective serotonin reuptake inhibitors. Results Ten children (25.6%) had either coagulation or platelet function abnormalities. Abnormal coagulation was identified in 5 children, and abnormal platelet function was discovered in 6. A diagnosis of TSC was associated with a platelet function abnormality (p = 0.012), whereas children without TSC had a higher rate of coagulopathy (p = 0.041). None of the other characteristics reached statistical significance. In 2 patients (5.1%) with TSC and platelet aggregation abnormalities, the authors noted normal standard screening laboratory studies and an uneventful detailed personal and family history. One of these 2 patients developed a significant intraoperative bleeding complication. Conclusions A preoperative screening with standard laboratory studies and detailed history may not be adequate to fully examine underlying coagulation abnormalities in children with refractory epilepsy. Platelet aggregation studies should be considered in patients with TSC