Francine Blei, M.D.

100 questions & answers about vascular anomalies
Blei, Francine; Anglin, Carlita
Sudbury, Mass. : Jones and Bartlett Publishers, 2011,
— id: 2179, year: 2011, vol: , page: , stat: ,

Coagulation abnormalities in children undergoing epilepsy surgery
Pacione, Donato; Blei, Francine; Devinsky, Orrin; Weiner, Howard L; Roth, Jonathan
2011 Jun;7(6):654-659, Journal of Neurosurgery: Pediatrics
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
— id: 134073, year: 2011, vol: 7, page: 654, stat: Journal Article,

Congenital minor salivary gland sialoblastoma: a case report and review of the literature
Saffari, Yasi; Blei, Francine; M Warren, Stephen; Milla, Sarah; Greco, M Alba
2011 ;30(1):32-39, Fetal & pediatric pathology
Sialoblastoma is the most common epithelial tumor of the salivary gland. We report a case of congenital sialoblastoma arising in a minor salivary gland of the buccal mucosa of a male infant. After radiologic evaluation, an incisional biopsy was performed and then the mass was excised en bloc. Histologic features were both favorable and unfavorable. However, there was no recurrence for 5 months. In spite of a reported histologic grading system, the clinical course of isolated sialoblastoma is considered unpredictable. More published case reports of this rare tumor may enable histologic and clinical correlation in order to accurately predict prognosis
— id: 120650, year: 2011, vol: 30, page: 32, stat: Journal Article,

Rapidly involuting congenital haemangioma associated with transient thrombocytopenia and coagulopathy: a case series
Baselga, E; Cordisco, M R; Garzon, M; Lee, M T; Alomar, A; Blei, F
2008 Jun;158(6):1363-1370, British journal of dermatology
Rapidly involuting congenital haemangioma (RICH) may present with thrombocytopenia, low fibrinogen and elevated fibrin degradation products and D-dimers. Such complications have rarely been reported. We wished to define the clinical characteristics of the thrombocytopenia and coagulopathy associated with RICH, to emphasize the transient nature of this haematological complication and to distinguish these abnormalities from true Kasabach-Merritt phenomenon (KMP). We present a case series of seven patients with large RICH who presented with thrombocytopenia and coagulopathy during the first week of life. Clinical and haematological characteristics were recorded retrospectively. Two of the patients were treated with embolization due to early signs of high-output cardiac failure; four patients received oral corticosteroids in the range of 2 mg kg(-1) daily; one patient did not receive any treatment in the neonatal period, although the tumour was excised at 6 months of age. Two patients with platelet counts lower than 10 x 10(9) L(-1) received a platelet transfusion. There were no bleeding complications and only one patient presented with petechiae. In all seven patients, platelet counts started to increase at > 2 weeks of age and the coagulopathy resolved. We conclude that RICH may present with thrombocytopenia and coagulopathy similar to mild KMP early in the neonatal period. However, in contrast to true KMP, these abnormal laboratory findings are self-limited and are usually not complicated by bleeding problems
— id: 78370, year: 2008, vol: 158, page: 1363, stat: Journal Article,

Optimizing quality of life for pediatric hematology and oncology patients: Perspectives from the Stephen D. Hassenfeld children's center for cancer and blood disorders
Blei F.; Manzano K.
2008 ;15(7):43-48, Primary Psychiatry
The articles in this issue underscore the variety of innovative programs and techniques essential to a pediatric and young adult day hospital setting. While patients at the Stephen D. Hassenfeld Children's Center for Cancer and Blood Disorders (SDHCC) at New York University (NYU) Langone Medical Center have hematologic or oncologic disorders, the facility design, programming, and philosophies discussed can be universally applied to any patient
— id: 81076, year: 2008, vol: 15, page: 43, stat: Journal Article,

Congenital lymphatic malformations
Blei, Francine
2008 ;1131:185-194, Annals of the New York Academy of Sciences
'Vascular anomalies' represents a spectrum of vascular lesions, of unclear etiology and often with unpredictable behavior. Patients with vascular anomalies represent a unique population, in that they have focal aberrations of vascular development (in vascular malformations) or vascular proliferation (in hemangiomas). The etiology of these disorders is unclear, and likely represents a multifactorial process. Vascular anomalies are an attractive model for the study of human disorders of vasculogenesis (development of the vasculature) and angiogenesis (new vessel growth from existing vessels)
— id: 79566, year: 2008, vol: 1131, page: 185, stat: Journal Article,

Literature watch. Adrenomedullin signaling is necessary for murine lymphatic vascular development
Blei, Francine
2008 ;6(1):45-59, Lymphatic Research & Biology
— id: 95164, year: 2008, vol: 6, page: 45, stat: Journal Article,

Vascular malformations and upper extremity anomalies associated with a subtelomeric microdeletion of chromosome 4p
Khonsari, Roman Hossein; Blechman, Keith M; Michaels, Joe; Vigler, Mordechai; Chiu, David T W; Wallerstein, Robert; Blei, Francine
2008 Jul;17(3):193-194, Clinical dysmorphology
— id: 95162, year: 2008, vol: 17, page: 193, stat: Journal Article,

Hemangiomatosis in Two Sets of Premature Twins
Laverdiere, Michele; Aggarawal, Renu; Blei, Francine
2008 May;25(5):295-300, American journal of perinatology
We attempted to identify the association of multifocal hemangiomas, specifically hepatic hemangiomatosis, in twins. We retrospectively reviewed our database of infants with hemangiomas, identifying those twins who both had hemangiomas, and we report two cases of twins with hemangiomatosis, including hepatic hemangiomas. Of 39 sets of twins in our Hemangioma Program, both twins had hemangiomas in seven twin sets. Of these seven sets, only the two reported in this article had hemangiomatosis. There were also five sets of triplets, with one set having two siblings affected by hemangiomas. We concluded that although hemangiomas in multiple gestation infants is well known, hemangiomatosis including hepatic hemangiomatosis is unusual
— id: 78368, year: 2008, vol: 25, page: 295, stat: Journal Article,

More than skin deep: a case of congenital lamellar ichthyosis, lymphatic malformation, and other abnormalities
Small, Katherine; Ginsburg, Howard; Greco, M Alba; Sarita-Reyes, Carmen; Kupchik, Gabriel; Blei, Francine
2008 ;6(1):39-44, Lymphatic Research & Biology
ABSTRACT Consanguinity allows for the expression of rare genetic disorders. We present the first case of an infant, born to consanguineous parents, with congenital lamellar ichthyosis, congenital lymphatic malformation, congenital hypothyroidism, bilateral megaureter, benign external hydrocephalus, and syrinx of the spinal cord. We review the disorders, examine their genetic causes, and explore the genetic connection among them
— id: 78369, year: 2008, vol: 6, page: 39, stat: Journal Article,

Early surgical intervention for proliferating hemangiomas of the scalp: indications and outcomes
Spector, Jason A; Blei, Francine; Zide, Barry M
2008 Aug;122(2):457-462, Plastic & reconstructive surgery
BACKGROUND:: Large hemangiomas of the scalp, though uncommon, present unique challenges to the reconstructive surgeon. If not treated early, these lesions can result in large areas of alopecia, distortion of the hairline, or deformation of the ear. Given these potential complications and the relative pliability and redundancy of the infant scalp before 4 months of age, the authors propose early surgical excision. METHODS:: A retrospective review of the senior author's (B.M.Z.) patient records was performed; over a period of 4 years, six infants were identified who underwent resection of a large scalp hemangioma. The surgical planning and execution of each case and follow-up are detailed. RESULTS:: All six hemangiomas were excised completely. In five cases, the excisions were performed in one stage at or before 4 months of age. In a sixth case, a tissue expander was placed before excision and closure in an 18-month-old infant. In three cases, significant ear malposition was corrected by removal of the deforming mass. There were no complications. CONCLUSIONS:: The authors have demonstrated that by taking advantage of the greater elasticity of the infant scalp, large hemangiomas of the scalp can be aggressively and successfully treated with surgical intervention, often in one operation. Beyond the usual indications, early surgical excision of scalp hemangiomas may be advantageous and warranted to prevent the development of large alopecic areas or the permanent distortion of the hairline and aural anatomy
— id: 94119, year: 2008, vol: 122, page: 457, stat: Journal Article,

Literature watch. Blood and lymphatic endothelial cell-specific differentiation programs are stringently controlled by the tissue environment
Blei, F
2007 ;5(1):49-65, Lymphatic Research & Biology
— id: 75164, year: 2007, vol: 5, page: 49, stat: Journal Article,

Literature watch
Blei, Francine
2007 ;5(3):203-214, Lymphatic Research & Biology
— id: 75161, year: 2007, vol: 5, page: 203, stat: Journal Article,

Literature watch. Rapamycin, a specific inhibitor of the mammalian target of rapamycin, suppresses lymphangiogenesis and lymphatic metastasis
Blei, Francine
2007 ;5(2):135-146, Lymphatic Research & Biology
— id: 75162, year: 2007, vol: 5, page: 135, stat: Journal Article,

Literature watch: Lineage tracing demonstrates the venous origin of the mammalian lymphatic vasculature
Blei, Francine
2007 ;5(4):275-276, Lymphatic Research & Biology
— id: 95163, year: 2007, vol: 5, page: 275, stat: Journal Article,

Splenic infarction due to concomitant hereditary spherocytosis and sickle cell trait
Dulman, Robin Yates; Buchanan, George R; Ginsburg, Howard; Fefferman, Nancy R; Greco, M Alba; Borys, Dariusz; Blei, Francine
2007 Dec;42(12):2129-2131, Journal of pediatric surgery
Concomitant hereditary spherocytosis and sickle cell trait, although extremely rare, could potentially lead to splenic sequestration or infarction. We report here the first case of splenic infarction in a child with hereditary spherocytosis and sickle cell trait while flying on a commercial aircraft. The presence of hypoxia, hemoconcentrated erythrocytes, and sickle hemoglobin created the perfect environment for clinical sequelae
— id: 75677, year: 2007, vol: 42, page: 2129, stat: Journal Article,

Surgical treatment of capillary hemangiomas causing amblyopia
Levi, Michelle; Schwartz, Shirah; Blei, Francine; Ceisler, Emily; Steele, Mark; Furlan, Louis; Millman, Arthur; Kodsi, Sylvia R
2007 Jun;11(3):230-234, Journal of AAPOS: American Association for Pediatric Ophthalmology & Strabismus
BACKGROUND: Capillary hemangiomas of the eyelids and orbit can cause refractive and occlusive amblyopia. Although oral and intralesional steroid injections are the most common treatment modalities, sometimes they are not successful. There is a paucity of information in the literature on the success of eliminating amblyogenic factors by treating these lesions with surgical resection. METHODS: Retrospective chart review of 10 patients in two pediatric ophthalmology practices who underwent surgical excision of a capillary hemangioma that was causing amblyopia and that had failed to regress with other treatment. RESULTS: Two patients had surgery secondary to pupillary occlusion, which was successful in relieving occlusion. Eight patients had surgery secondary to significant astigmatism. The average preoperative astigmatic difference between the affected and unaffected eye in five of these patients undergoing surgery before the age of 21 months was 2.15 D. The average postoperative astigmatic difference was 0.1 D. The average preoperative astigmatic difference between the affected and unaffected eye in three patients undergoing surgery after 21 months of age was 1.6 D. Surgery completely failed to reduce the astigmatism in two of these patients. The third patient had a decrease of 0.75 D of cylinder but still had a difference of 1.75 D between the two eyes postoperatively. Postoperative complications in this study included wound infection in one patient. CONCLUSIONS: Surgical excision of capillary hemangiomas that were resistant to other modes of treatment was useful in relieving pupillary occlusion and in decreasing the amount of astigmatism if performed before the age of 21 months in our series of patients. Our cases as well as the literature suggest that surgery should be performed at 13 months or earlier to reduce the amount of astigmatism
— id: 71020, year: 2007, vol: 11, page: 230, stat: Journal Article,

Treatment of capillary hemangiomas causing refractive and occlusional amblyopia
Schwartz, Shirah R; Kodsi, Sylvia R; Blei, Francine; Ceisler, Emily; Steele, Mark; Furlan, Louis
2007 Dec;11(6):577-583, Journal of AAPOS: American Association for Pediatric Ophthalmology & Strabismus
PURPOSE: Capillary hemangiomas of the eyelid and orbit are treated when amblyopia secondary to anisometropic astigmatism or pupillary occlusion is present or when rapid growth of the hemangioma threatens to occlude the pupil. The goal of this study was to determine whether treatment of hemangiomas resolves or prevents occlusion or results in decrease in astigmatism. METHODS: The records of 54 patients who underwent treatment for reduction in the size of a capillary hemangioma causing amblyopia or threatened amblyopia in two pediatric ophthalmology practices were reviewed. RESULTS: Twenty-eight patients were treated for amblyopia due to anisometropic astigmatism. The average amount of pretreatment astigmatism was 2.71 D, while the average amount of post-treatment astigmatism was 0.46 D. Fifteen of these patients could be tested for optotype visual acuity and all had vision acuity of 20/40 or better. Only 1 of the 15 patients treated for threatened occlusion of the pupil developed occlusion. Six of these patients cooperated with optotype visual acuity and all had vision acuity of 20/30 or better. Eleven patients were treated for pupillary occlusion. Occlusion resolved in all cases. Of the five patients treated for occlusion who cooperated with optotype visual acuity, two had a vision acuity of 20/100 or worse. CONCLUSIONS: Treatment to reduce the size of capillary hemangiomas results in resolution of occlusion, reduction in astigmatism, and prevention of pupillary occlusion. Those with occlusion are at higher risk for severe residual amblyopia and require prompt and definitive treatment
— id: 75163, year: 2007, vol: 11, page: 577, stat: Journal Article,

Literature watch
Blei, Francine
2006 ;4(3):167-176, Lymphatic Research & Biology
— id: 68924, year: 2006, vol: 4, page: 167, stat: Journal Article,

Congenital plaque-type glomuvenous malformations presenting in childhood
Mallory, Susan Bayliss; Enjolras, Odile; Boon, Laurence M; Rogers, Erica; Berk, David R; Blei, Francine; Baselga, Eulalia; Ros, Anne-Marie; Vikkula, Miikka
2006 Jul;142(7):892-896, Archives of dermatology
BACKGROUND: Glomuvenous malformations (GVMs) are now considered a separate entity from venous malformations. The rarest type of GVM is the generalized congenital plaque-type GVM. OBSERVATIONS: We present 10 new cases of congenital plaque-type GVM and describe their clinical progression and treatment. Mutations in the glomulin gene were found in those patients who participated in the genetic study. CONCLUSIONS: Congenital plaque-type GVMs are unique in their congenital nature, extensive distribution, difficult to diagnose and treat, and progressive involvement after birth. Most cases are familial, yet affected relatives usually have only minor lesions. The lesions of congenital plaque-type GVM are severe, visible at birth, and usually mistaken for extensive venous malformations. Vascular malformations are divided by hemodynamic type into slow-flow and fast-flow lesions. Slow-flow lesions are subcategorized as capillary, lymphatic, and venous.(1) Capillary malformations are flat, sharply demarcated, red-pink vascular stains of the skin commonly referred to as port-wine stains. These persist throughout life and are characterized histologically by dilated capillaries within the dermis. They slowly increase in size with age. Lymphatic malformations are spongelike collections of abnormal channels and spaces that contain clear lymphatic fluid, causing an excess of fluid to accumulate and dilate the lymphatic channels. This results in swelling of the affected area and, if extensive, can cause enlargement of soft tissues and bones
— id: 68926, year: 2006, vol: 142, page: 892, stat: Journal Article,

No evidence for maternal-fetal microchimerism in infantile hemangioma: a molecular genetic investigation
Pittman, Kristianna M; Losken, H Wolfgang; Kleinman, Mark E; Marcus, Jeffrey R; Blei, Francine; Gurtner, Geoffrey C; Marchuk, Douglas A
2006 Nov;126(11):2533-2538, Journal of investigative dermatology
In this study, using the placental origin theory as a basis, we set out to explore whether hemangioma endothelial cells (HEC) were maternal in origin. We rigorously addressed this hypothesis using several molecular genetic techniques. Fluorescent in situ hybridization on surgical specimens of proliferating hemangiomas (n=8) demonstrated no XX-labeled HEC from resected tumors of male infants. This analysis was followed by PCR genotyping of HEC (n=11) using microsatellite markers where cellular components were genotyped and compared to genomic DNA of corresponding mother-child pairs. In the seven informative mother-child pairs, HEC matched the genotype of the child and not the maternal genotype. Concerned that HEC represented a mixed population of cells, we subsequently enriched for cells using the placental-specific endothelial cell (EC) marker, FcgammaRII. Three informative mother-child pairs exhibited only the genotype of the child in our enriched cell population. Using sequence analysis, we identified an informative single nucleotide polymorphism in an exon of the placental-EC-specific protein, GLUT1. When comparing GLUT1 complementary DNA (cDNA) with mother-child DNA, the genotype of the cDNA matched the constitutional DNA of the child. Our results indicate that hemangiomas are not microchimeric in origin. This study provides further insight into the origin of a tumor whose pathogenesis remains elusive.Journal of Investigative Dermatology (2006) 126, 2533-2538. doi:10.1038/sj.jid.5700516; published online 17 August 2006
— id: 68925, year: 2006, vol: 126, page: 2533, stat: Journal Article,

Risk factors for amblyopia in children with capillary hemangiomas of the eyelids and orbit
Schwartz, Shirah R; Blei, Francine; Ceisler, Emily; Steele, Mark; Furlan, Louis; Kodsi, Sylvia
2006 Jun;10(3):262-268, Journal of AAPOS: American Association for Pediatric Ophthalmology & Strabismus
Introduction: Capillary hemangiomas are the most common orbital tumors of childhood and can cause amblyopia secondary to occlusion of the pupil, anisometropia, or strabismus. We undertook this study to describe the clinical characteristics of children with capillary hemangiomas and to propose a classification system to guide clinical treatment decisions. Methods: A retrospective review of the records of 129 patients with 132 capillary hemangiomas in two pediatric ophthalmology practices was conducted. Hemangiomas were classified based on size. Presence of aniosometropic astigmatism, ptosis, pupillary occlusion, lid margin change, proptosis, globe displacement, and strabismus was recorded. Results: Thirty-one hemangiomas measured less than 1 cm in greatest dimension and were not associated with amblyogenic factors. Seventy-five patients had hemangiomas that measured greater than 1 cm, 40 of which were associated with amblyopia. Eighteen children had diffuse hemangiomas that could not be measured and 14 of these were associated with amblyopia. Five of seven hemangiomas in six patients with PHACES syndrome were associated with amblyopia. Conclusion: This study is the largest review of capillary hemangiomas of the orbit and eyelids. Our findings suggest that size greater than 1 cm in largest diameter is an important predictor of amblyogenic factors and approximately half of these patients will require treatment. Diffuse hemangiomas and hemangiomas in patients with PHACES syndrome will cause amblyopia in the majority of cases
— id: 66077, year: 2006, vol: 10, page: 262, stat: Journal Article,

Splenic infarction due to concomitant hereditary spherocytosis and sickle cell trait
Yates, R; Buchanan, GR; Ginsburg, H; Fefferman, N; Greco, MA; Borys, D; Blei, F
2006 NOV 16 ;108(11):8B-9B, Blood
— id: 71216, year: 2006, vol: 108, page: 8B, stat: Journal Article,

Periodontitis as a manifestation of chronic benign neutropenia
Zaromb, Allison; Chamberlain, Darren; Schoor, Robert; Almas, Khalid; Blei, Francine
2006 Nov;77(11):1921-1926, Journal of periodontology
BACKGROUND: A subcategory of chronic neutropenia is chronic benign neutropenia, which is characterized by a prolonged non-cyclic neutropenia as the sole abnormality, with no underlying disease to which the neutropenia can be attributed. Chronic neutropenia is defined as a low absolute neutrophil count for >6 months. In this presentation, periodontitis seems to be the sole manifestation of a juvenile patient with chronic benign neutropenia. A 7-year-old white male presented with periodontitis of the primary dentition and early tooth loss. His medical and dental history was otherwise unremarkable. Suspecting some systemic illness as the underlying cause, the patient was referred for a medical consultation and a series of blood tests. METHODS: Blood analyses included a complete blood count (CBC), sequential multiple analyzer 24 (SMA 24), glycated hemoglobin levels, and screening for anti-white blood cell antibodies. Blood levels of calcium, vitamin D, dihydroxyvitamin-D, phosphorus, and alkaline phosphatase were also measured. Liver function tests were performed. RESULTS: Following analysis of recent and previous blood test results, a diagnosis of chronic benign neutropenia was assigned. The patient's periodontal condition was treated with scaling and root planing, oral hygiene instruction, and antimicrobial mouthrinses. Three-month recall visits were recommended as a follow-up protocol. CONCLUSIONS: This case represents the importance of diagnosing periodontal disease as a possible indicator of underlying systemic disease. When a patient presents with an unusual, generalized form of periodontal disease, screening for systemic disorders is required, as the oral condition may be the first or only manifestation of a systemic abnormality. This case also illustrates the reason for the change in classification of such a condition to periodontitis as a manifestation of systemic disease. This condition was previously classified as prepubertal periodontitis, a disease diagnosis that focused on the patient's age at the onset of the disease rather than the etiology
— id: 71021, year: 2006, vol: 77, page: 1921, stat: Journal Article,

Foreword
Blei F
2005 ;3(4):218-218, Lymphatic Research & Biology
— id: 61599, year: 2005, vol: 3, page: 218, stat: Journal Article,

Basic science and clinical aspects of vascular anomalies
Blei, Francine
2005 Aug;17(4):501-509, Current opinion in pediatrics
PURPOSE OF REVIEW: Patients with vascular and lymphatic anomalies are often 'medical orphans' ascertained through distinct medical specialists. Multidisciplinary vascular anomalies programs provide focused expertise in diagnosis and treatment for patients. National and international workshops on vascular anomalies are fostering clinical and basic science research to enhance our understanding of vascular development and vascular anomalies. Herewith is presented an update of recent advances in the study of vascular/lymphatic anomalies. RECENT FINDINGS: New original findings include (1) the identification of distinct cell surface markers and other cellular properties in hemangiomas and vascular malformations relevant to vascular development, (2) the discovery of novel genetic mutations and susceptibility genes in patients with vascular anomalies, (3) recognition of new risk stratifications and clinical issues for patients with hemangiomas and vascular malformations, and (4) the elucidation of sequelae from the disorders as well as side effects of recent and previous therapies for vascular anomalies. SUMMARY: Vascular anomalies are an attractive model for the study of human disorders of vasculogenesis and angiogenesis. The etiology of these disorders is unclear and likely represents a multifactorial process. Clinical clues are leading to scientific investigations that may enable targeted therapies, prevention strategies, or both
— id: 57829, year: 2005, vol: 17, page: 501, stat: Journal Article,

Kaposiform hemangioendothelioma without Kasabach-Merritt phenomenon
Gruman, Alla; Liang, Marilyn G; Mulliken, John B; Fishman, Steven J; Burrows, Patricia E; Kozakewich, Harry P W; Blei, Francine; Frieden, Ilona J
2005 Apr;52(4):616-622, Journal of the American Academy of Dermatology
Kasabach-Merritt phenomenon is a serious coagulopathy associated with kaposiform hemangioendothelioma (KHE), tufted angioma, and possibly other vascular neoplasms. KHE presenting in the absence of Kasabach-Merritt phenomenon is rare, although tufted angioma frequently occurs without thrombocytopenia. We retrospectively reviewed 10 cases of KHE without Kasabach-Merritt phenomenon. The tumors appeared as soft tissue masses with the overlying skin being either normal, erythematous, or violaceous. There were no radiologic or microscopic differences in noncoagulopathic KHE as compared with coagulopathic KHE. Evidence of platelet trapping and hemosiderin deposition was seen histologically, despite normal serum platelet levels. All KHE were less than 8 cm in diameter, suggesting that tumors that grow no larger than this size are less likely to trap platelets in sufficient quantity to cause thrombocytopenia. Our series confirms that KHE appears with a wide spectrum of behavior and response to treatment. The decision as to whether or not to treat a noncoagulopathic KHE should be based on the size and location of the tumor and the possible side effects of therapy
— id: 57831, year: 2005, vol: 52, page: 616, stat: Journal Article,

Circulating endothelial progenitor cells and vascular anomalies
Kleinman, Mark E; Blei, Francine; Gurtner, Geoffrey C
2005 ;3(4):234-239, Lymphatic Research & Biology
Recent findings regarding pathways of stem/progenitor cell involvement in adult blood vessel growth (postnatal vasculogenesis) suggest new theories for the pathogenesis of vascular anomalies. The somatic growth of vascular malformations and the mysterious pattern of proliferation and involution in infantile hemangioma can no longer be purely understood through the paradigm of angiogenesis. Molecular signals for postnatal vasculogenesis are being discovered in numerous animal models of cancer and ischemia, yet little research has addressed the importance of vasculogenesis in the growth of vascular anomalies. In this review, we discuss early studies that have investigated stem/progenitor cell involvement in the pathophysiology of infantile hemangioma and other congenital vascular anomalies
— id: 61598, year: 2005, vol: 3, page: 234, stat: Journal Article,

Ocular and systemic manifestations of PHACES (Posterior fossa malformations, Hemangiomas, Arterial anomalies, Cardiac defects and coarctation of the Aorta, Eye abnormalities, and Sternal abnormalities or ventral developmental defects) syndrome
Kronenberg, Alaina; Blei, Francine; Ceisler, Emily; Steele, Mark; Furlan, Louis; Kodsi, Sylvia
2005 Apr;9(2):169-173, Journal of AAPOS: American Association for Pediatric Ophthalmology & Strabismus
INTRODUCTION: PHACES syndrome (Posterior fossa malformations, Hemangiomas, Arterial anomalies, Cardiac defects and coarctation of the aorta, Eye abnormalities, and Sternal abnormalities or ventral developmental defects) is a rare neurocutaneous syndrome with only 2 case reports published in the ophthalmic literature. This study was conducted to identify ocular and systemic manifestations of PHACES syndrome. METHODS: A retrospective chart review was performed on 8 children with a diagnosis of PHACES syndrome. Information recorded included age at first visit, length of follow-up, gender, race, vision, need for glasses, strabismus, amblyopia, ptosis, proptosis, anterior and posterior segment abnormalities, need for treatment of the hemangioma, type of treatment of the hemangioma, and systemic manifestations. RESULTS: Periocular and ocular findings in patients with PHACES syndrome included hemangioma involving ocular structures (n = 6), strabismus (n = 4), amblyopia (n = 5), proptosis (n = 2), ptosis (n = 5), anterior polar cataract (n = 1), optic atrophy from optic neuropathy (n = 1), heterochromia (n = 1), and refractive error requiring glasses (n = 2). All patients were treated with steroids for the hemangioma. Systemic manifestations of PHACES syndrome included posterior fossa malformation (n = 4), hemangioma (n = 8), arterial anomalies (n = 3), cardiac abnormalities (n = 3), and sternal or ventral deformities (n = 3). CONCLUSION: Children with PHACES syndrome may have significant ocular and systemic abnormalities and are at increased risk for strabismus and amblyopia. They often require steroid therapy of the hemangioma to prevent and/or treat ocular complications. These patients require careful monitoring by a pediatric ophthalmologist in addition to other subspecialists
— id: 57830, year: 2005, vol: 9, page: 169, stat: Journal Article,

The role of pediatric cardiology in the management of hemangiomas
Rutkowski, M; Blei, F
2005 ;3(4):260-262, Lymphatic Research & Biology
— id: 62531, year: 2005, vol: 3, page: 260, stat: Journal Article,

Lipoblastoma of infancy mimicking hemangioma of infancy
Steckman, David; Zide, Barry; Greco, M Alba; Rivera, Rafael; Blei, Francine
2005 Sep-Oct;7(5):326-330, Archives of facial plastic surgery
Lipoblastomas are rare benign tumors of infancy that usually affect children younger than 3 years. Most lipoblastomas (70%) occur on the extremities. Lipoblastomas may mimic other infantile tumors, including hemangiomas, hibernomas, lipomas, and liposarcomas, and correct diagnosis is necessary to ensure appropriate treatment. Lipoblastomas fall under 2 discrete subtypes: well-circumscribed lipoblastomas and diffuse lipoblastomatosis. Both types present with firm, nontender masses of lobulated, well-circumscribed soft tissue. Histologically they can be highly vascularized with plexiform capillaries, often with an individual feeder artery to each lobule. Complete surgical removal is the recommended treatment. Only 2 cases of lipoblastomas of the cheek have been reported in the English-language literature. We present the case of a young child with a cheek lipoblastoma, emphasizing the importance of correct diagnosis and highlighting techniques used to provide suitable treatment
— id: 61366, year: 2005, vol: 7, page: 326, stat: Journal Article,

Periocular hemangiomas: what every physician should know
Ceisler, Emily J; Santos, Laura; Blei, Francine
2004 Jan-Feb;21(1):1-9, Pediatric dermatology
Hemangiomas are the most common benign tumor of infancy. Most hemangiomas remain asymptomatic and can be managed by close observation; however, immediate treatment is indicated for hemangiomas that may cause significant complications. Periocular hemangiomas warrant close evaluation and early, active treatment of those with the potential to threaten or permanently compromise vision. Herein we review the clinical features of periocular hemangiomas, differential diagnosis, possible ophthalmologic complications and sequelae, and therapeutic modalities
— id: 44856, year: 2004, vol: 21, page: 1, stat: Journal Article,

Obstetric management of Klippel-Trenaunay syndrome
Rebarber, Andrei; Roman, Ashley S; Roshan, Daniel; Blei, Francine
2004 Nov;104(5 Pt 2):1205-1208, Obstetrics & gynecology
BACKGROUND: Klippel-Trenaunay syndrome is a rare congenital disease characterized by extensive cutaneous vascular malformations, venous varicosities, focal abnormalities of the deep venous system, and underlying soft tissue or bony hypertrophy. Given the rarity of the disease, there is little information available to counsel patients with Klippel-Trenaunay syndrome regarding obstetric outcome. CASES: We report our experience with 3 patients in whom Klippel-Trenaunay syndrome complicated 4 pregnancies. Successful delivery of a healthy infant at or beyond 36 weeks of gestation was achieved in all pregnancies. One of the 4 pregnancies was complicated by pulmonary embolism. CONCLUSION: Klippel-Trenaunay syndrome was once thought to be a contraindication to pregnancy. With careful management, successful pregnancies can be achieved
— id: 47771, year: 2004, vol: 104, page: 1205, stat: Journal Article,

Transiently arterialized hemangiomas: relevant clinical and cardiac issues
Blei, Francine; Rutkowski, Monika
2003 ;1(4):317-320, Lymphatic Research & Biology
Although the majority of hemangiomas of infancy undergo an uncomplicated, predictable course of proliferation followed by involution, a subset of patients sustain a more fastidious course. These include hemangiomas that, at least during part of their life cycle, have a high flow (arterial) component. Hemangiomas with high flow are most frequently located in the liver. These lesions can lead to significant morbidity, with high output cardiac failure. We have identified nonhepatic hemangiomas that have an apparent propensity to develop a high flow element--the parotid, upper arm, scalp, and rarely the upper lip--and present our experience in this report. These lesions appear to behave as transiently 'arterialized' hemangiomas
— id: 48087, year: 2003, vol: 1, page: 317, stat: Journal Article,

Ophthalmic issues in hemangiomas of infancy
Ceisler, Emily; Blei, Francine
2003 ;1(4):321-330, Lymphatic Research & Biology
Hemangiomas are the most common benign tumor of infancy. Although most hemangiomas remain asymptomatic, certain hemangiomas can cause significant morbidity and require treatment. Periocular hemangiomas require close observation and early therapy for those lesions with potential for visual impairment. Hemangiomas typically cause visual morbidity by induction of amblyopia, strabismus, significant refractive error or optic nerve compromise. Diagnosis is typically straightforward but occasionally other entities may cause diagnostic confusion and radiologic evaluation can be helpful. This is particularly important if the hemangioma is one component of the PHACES syndrome. Therapeutic options which may be useful include steroids (oral, intralesional or topical), interferon alpha (usually reserved for life- or sight-threatening lesions due to serious potential side effects), laser, embolization and surgery. Ophthalmic treatment using patching, atropine, glasses and stabismus surgery may be necessary
— id: 48088, year: 2003, vol: 1, page: 321, stat: Journal Article,

Genetics of vascular anomalies: an update
Chaft, Jamie E; Steckman, David A; Blei, Francine
2003 ;1(4):283-289, Lymphatic Research & Biology
Vascular anomalies arise from genetic, environmental, mechanical, and/or hormonal factors. Some are inherited in a Mendelian fashion whereas others result from abnormal chromosomal segregation during gametogenesis or appear sporadically during various stages of life. Understanding the molecular basis of vascular development and vascular anomalies provides potential tools for diagnosis and treatment of the diseases
— id: 48085, year: 2003, vol: 1, page: 283, stat: Journal Article,

Prenatal diagnosis of vascular anomalies: update and review of the literature
Chaft, Jamie; Blei, Francine
2003 ;1(4):309-312, Lymphatic Research & Biology
Optimal care for a subgroup of infants with complicated vascular anomalies requires prenatal diagnosis. Fetal vascular lesions are either vascular tumors or vascular malformations, both of which are often detected on routine ultrasound. Imaging, such as ultrasound and fetal MRI, can be used to examine lesions and provide the data for a differential diagnosis, which may impact the course of care both in utero and postnatally. Prenatal diagnosis provides the opportunity for antenatal intervention, parental counseling, and planning of the mode and location of delivery to optimize postnatal care. Prenatal diagnosis of vascular lesions also serves to alert the physician to the potential for associated syndromes and complications. Any indication of a vascular anomaly should be referred for further examination by an experienced multidisciplinary team of physicians to ensure the window in which evaluation, planning, and treatment can take place is not missed
— id: 48086, year: 2003, vol: 1, page: 309, stat: Journal Article,

Increased circulating AC133+ CD34+ endothelial progenitor cells in children with hemangioma
Kleinman, Mark E; Tepper, Oren M; Capla, Jennifer M; Bhatt, Kirit A; Ceradini, Daniel J; Galiano, Robert D; Blei, Francine; Levine, Jamie P; Gurtner, Geoffrey C
2003 ;1(4):301-307, Lymphatic Research & Biology
Hemangioma is the most common soft-tissue tumor of infancy. Despite the frequency of these vascular tumors, the origin of hemangioma-endothelial cells is unknown. Circulating endothelial progenitor cells (EPCs) have recently been identified as vascular stem cells with the capacity to contribute to postnatal vascular development. We have attempted to determine whether circulating EPCs are increased in hemangioma patients and thereby provide insight into the role of EPCs in hemangioma growth. METHODS AND RESULTS: Peripheral blood mononuclear cells (PBMCs) were isolated from hemangioma patients undergoing surgical resection (N = 5) and from age-matched controls (N = 5) undergoing strabismus correction surgery. PBMCs were stained with fluorescent-labeled antibodies for AC133, CD34, and VEGFR2/KDR. Fluorescent-labeled isotype antibodies served as negative controls. Histologic sections of surgical specimens were stained with the specific hemangioma markers Glut1, CD32, and merosin, to confirm the diagnosis of common hemangioma of infancy. EPCs harvested from healthy adult volunteers were stained with Glut1, CD32, and merosin, to assess whether cultured EPCs express known hemangioma markers. Hemangioma patients had a 15-fold increase in the number of circulating CD34 AC133 dual-staining cells relative to controls (0.78+/-0.14% vs.0.052+/-0.017%, respectively). Similarly, the number of PBMCs that stained positively for both CD34 and KDR was also increased in hemangioma patients (0.49+/-0.074% vs. 0.19+/-0.041% in controls). Cultured EPCs stained positively for the known hemangioma markers Glut1, CD32, merosin. CONCLUSIONS: This is the first study to suggest a role for EPCs in the pathogenesis of hemangioma. Our results imply that increased levels of circulating EPCs may contribute to the formation of this vascular tumor
— id: 49078, year: 2003, vol: 1, page: 301, stat: Journal Article,

The role of magnetic resonance imaging in the management of vascular malformations of the trunk and extremities
Rinker, Brian; Karp, Nolan S; Margiotta, Michael; Blei, Francine; Rosen, Robert; Rofsky, Neil M
2003 Aug;112(2):504-510, Plastic & reconstructive surgery
Vascular malformations can usually be diagnosed on clinical grounds. They have a well-defined appearance on magnetic resonance imaging, which can effectively determine their tissue and flow characteristics. However, the role of cross-sectional imaging in the management of vascular malformations is not well defined. Most reviews suggest that magnetic resonance imaging should be reserved for cases in which the extent of the lesion cannot be estimated on physical examination. However, to date no group has compared the accuracy of physical examination alone to that of magnetic resonance imaging in determining this extent. A review was performed of all the patients evaluated for vascular malformations at the New York University Trunk and Extremity Vascular Anomalies Conference between July of 1994 and August of 1999. Patients who underwent magnetic resonance evaluation at other institutions and whose images were not available for review were excluded. All study patients either underwent magnetic resonance imaging examination at New York University Medical Center or had outside films reviewed at the center. The physical examination findings were compared with the magnetic resonance findings and the surgeon and radiologist made a joint decision about whether there was a correlation between the magnetic resonance and physical examination findings. Fifty-eight patients met the study criteria, 44 (76 percent) of whom were found to have more extensive disease on magnetic resonance examination than appreciated on physical examination. Of the 51 patients with low-flow vascular malformations (venous vascular malformations, lymphatic malformations, and capillary malformations), 39 (76 percent) had more extensive disease on magnetic resonance examination than on physical examination. Of the seven patients with high-flow arteriovenous malformations, five had more extensive disease on magnetic resonance. In all of the 44 patients whose magnetic resonance imaging findings did not correlate with those of the physical examination, therapeutic decision making was affected. Contrary to the conventional wisdom of published reviews, physical examination findings significantly underestimated the extent of vascular malformations in the majority of cases. Magnetic resonance imaging should be performed in all patients with vascular malformations of the trunk and extremities before therapy is planned. In an age when physicians are asked to justify their decisions, especially where the use of expensive diagnostic modalities is concerned, the situations in which these tests are indispensable must be clearly defined or else patients will be denied access to them
— id: 38870, year: 2003, vol: 112, page: 504, stat: Journal Article,

Vascular anomalies: From bedside to bench and back again
Blei, Francine
2002 Mar;32(3):72-93, Current problems in pediatric & adolescent health care
— id: 39665, year: 2002, vol: 32, page: 72, stat: Journal Article,

Somatic mutation of vascular endothelial growth factor receptors in juvenile hemangioma
Walter, Jeffrey W; North, Paula E; Waner, Milton; Mizeracki, Adam; Blei, Francine; Walker, John W T; Reinisch, John F; Marchuk, Douglas A
2002 Mar;33(3):295-303, Genes, chromosomes & cancer
Juvenile hemangiomas are the most common tumors of infancy, occurring in as many as 10% of all births. These benign vascular lesions enlarge rapidly during the first year of life by hyperplasia of endothelial cells and attendant pericytes and then spontaneously involute over a period of years, leaving loose fibrofatty tissue. Several hypotheses have been put forth concerning hemangiogenesis, including the possibility that the tumor is the result of somatic mutation in one or more components of critical vascular growth-regulatory pathways. To test this hypothesis, we obtained 15 proliferative-phase hemangiomas after surgical resection and dissected them to enrich for the lesional (endothelial and pericytic) components of each specimen. To determine whether hemangiomas represent a clonal expansion from a single progenitor cell, we assayed X-inactivation patterns for each lesion by using the polymorphic X-linked human androgen receptor gene. Twelve of 14 informative hemangiomas showed a significant degree of allelic loss after methylation-based and transcription-based polymerase chain reaction clonality assays, suggesting a nonrandom X-inactivation pattern and, thus, a monoclonal origin. We then sequenced genes encoding the receptors of the vascular endothelial growth factors (VEGFs) as candidates for potential somatic mutation. Mutations were found in two of the 15 hemangioma specimens: a missense mutation (P1147S) in the kinase domain of the VEGFR2 (FLK1/KDR) gene in one specimen and a missense mutation (P954S) in the kinase insert of the VEGFR3 (FLT4) gene in another specimen. In each case, the mutation was detected in tumor tissue but not in adjacent normal tissue. These results suggest that one potential mechanism involved in hemangioma formation is the alteration of the VEGF signaling pathway in endothelial and/or pericytic cells
— id: 57832, year: 2002, vol: 33, page: 295, stat: Journal Article,

Severe anemia due to gastrointestinal hemorrhage as the presenting symptom in an adolescent female with gastrointestinal stromal cell tumor
Wistinghausen, B; Rivera, R; Ginsberg, H; Blei, F
2002 NOV 16 ;100(11):4B-4B, Blood
— id: 37128, year: 2002, vol: 100, page: 4B, stat: Journal Article,

Deep vein thrombosis associated with May-Thurner syndrome in two adolescents
Wistinghausen, B; Rosen, R; Blei, F
2002 NOV 16 ;100(11):114B-114B, Blood
— id: 37130, year: 2002, vol: 100, page: 114B, stat: Journal Article,

Evidence for loss of heterozygosity of 5q in sporadic haemangiomas: are somatic mutations involved in haemangioma formation?
Berg JN; Walter JW; Thisanagayam U; Evans M; Blei F; Waner M; Diamond AG; Marchuk DA; Porteous ME
2001 Mar;54(3):249-252, Journal of clinical pathology
BACKGROUND/AIMS: Haemangiomas are common benign tumours of infancy that consist of rapidly proliferating endothelial cells. A locus for an autosomal dominant predisposition to haemangioma has been identified recently on chromosome 5q. This study aimed to investigate loss of heterozygosity on chromosomes 5 and 9 in haemangiomas. METHODS: Sporadic proliferative phase haemangiomas were microdissected. Polymerase chain reaction amplification and analysis of microsatellite markers on chromosomes 5 and 9 was carried out. RESULTS: There was a significant loss of heterozygosity for markers on chromosome 5q in haemangioma tissue, when compared with either markers from chromosome 5p (p < 0.05) or markers from chromosome 9 (p < 0.05). CONCLUSIONS: These results suggest that haemangioma formation might be associated with somatic mutational events, and provides evidence that a locus on 5q is involved in the formation of sporadic haemangiomas
— id: 19443, year: 2001, vol: 54, page: 249, stat: Journal Article,

Treatment of hemolytic disease of the newborn caused by anti-Kell antibody with recombinant erythropoietin
Dhodapkar KM; Blei F
2001 Jan;23(1):69-70, Journal of pediatric hematology/oncology
Recent data suggest that antibody-mediated suppression of erythroid progenitors may contribute to the anti-Kell-induced alloimmune hemolytic disease of the newborn (HDN). A 32-week-old girl who was positive for Kell was born to a mother who was negative for Kell but known to have anti-Kell antibodies. After birth, the baby had HDN and hyperbilirubinemia develop (peak bilirubin 21 mg/dL at day 9 of life). which was treated with phototherapy. Although the hyperbilirubinemia resolved, she became progressively anemic (hematocrit 22%) with an inappropriately low reticulocyte response (1.1%) and erythropoietin (EPO) level (20 mU/mL). To avoid the need for a blood transfusion, she was treated with recombinant erythropoietin (rEPO) and oral iron supplements. One week after starting EPO, the reticulocyte count increased to 9.1%. Erythropoietin therapy was continued for a total of 9 weeks, with resolution of her anemia at the end of therapy (hematocrit 35%). Thus, we were able to successfully treat the anemia with rEPO with avoidance of blood transfusion. This patient demonstrates that the antibody-mediated erythroid suppression in Kell alloimmune anemia can be overcome by rEPO. Recombinant erythropoietin should therefore be considered in the management of infants with severe or hypoproliferative anti-Kell-associated anemia
— id: 19444, year: 2001, vol: 23, page: 69, stat: Journal Article,

Somatic mutations in sporadic juvenile hemangioma
Walter, JW; North, PE; Mizeracki, A; Waner, M; Reinisch, JF; Walker, J; Blei, F; Patterson, C; Marchuk, DA
2001 OCT ;69(4):554-554, American journal of human genetics
— id: 54825, year: 2001, vol: 69, page: 554, stat: Journal Article,

Human coagulation factor FVIIa (recombinant) in the management of limb-threatening bleeds unresponsive to alternative therapies: results from the NovoSeven emergency-use programme in patients with severe haemophilia or with acquired inhibitors
Arkin S; Blei F; Fetten J; Foulke R; Gilchrist GS; Heisel MA; Key N; Kisker CT; Kitchen C; Shafer FE; Shah PC; Strickland D
2000 Apr;11(3):255-259, Blood coagulation & fibrinolysis
This open-label, emergency-use study evaluated the efficacy and safety of activated human coagulation factor VIIa (recombinant) (rFVIIa) (NovoSeven; Novo Nordisk Pharmaceuticals, Inc., New Jersey, USA) in treating limb-threatening joint or muscle bleeds in 17 patients with haemophilia A or B and six patients with acquired inhibitors to factor VIII or factor IX. All patients had previously failed on one or more alternative therapies. rFVIIa administration was effective or partially effective in controlling joint or muscle bleeds in 34 out of 35 (97%) bleeding episodes; in 23 patients, 14 of 17 (82%) muscle bleeds and 16 of 18 (89%) joint bleeds were effectively controlled. These findings suggest that rFVIIa is an effective and well-tolerated therapeutic option in the management of joint or muscle haemorrhage in patients with haemophilia and in patients with acquired inhibitors
— id: 19445, year: 2000, vol: 11, page: 255, stat: Journal Article,

New clinical observations in hemangiomas
Blei F
1999 Sep;18(3):187-194, Seminars in cutaneous medicine & surgery
Much research in endothelial biology is aimed at developing methods to stimulate productive angiogenesis or inhibit unwanted angiogeneseis. Hemangiomas provide a model for endothelial proliferation and involution. This article is intended to update the reader with new information regarding hemangiomas of infancy, the most common tumor of childhood. Topics such as possible origin, management issues, and psychosocial stresses are addressed. This field is constantly changing, but an effort has been made to include most of the recently reported articles. Our hope is that this information will enable physicians caring for patients with hemangiomas to better address the concerns of their patients and families
— id: 7959, year: 1999, vol: 18, page: 187, stat: Journal Article,

Genetic mapping of a novel familial form of infantile hemangioma
Walter JW; Blei F; Anderson JL; Orlow SJ; Speer MC; Marchuk DA
1999 Jan 1;82(1):77-83, American journal of medical genetics
Infantile hemangiomas are the most common tumor of infancy, occurring with an incidence of up to 10% of all births. They are benign but highly proliferative lesions involving aberrant localized growth of capillary endothelium. Although most hemangiomas occur sporadically and as single lesions, or in conjunction with pleiotropic genetic syndromes, we have previously identified six kindreds where hemangiomas appear to segregate as an autosomal dominant trait with high penetrance. Four such families contain affected individuals in three or more generations. In the current study, blood samples from five of these families were collected and used in a whole genome linkage search at 10-cM resolution. We established evidence for linkage to 5q in three families, and evidence for locus heterogeneity. The three 5q-linked families were further genotyped to generate haplotype information and narrow the candidate interval. Based on recombination breakpoint analysis, the interval exists between markers D5S2490 and D5S408, spanning 55 cM, and corresponding to 5q31-33. Using information from affected and unaffected individuals, the interval spans 38 cM between markers D5S1469 and D5S211. Three candidate genes involved with blood vessel growth map to this region: fibroblast growth factor receptor-4 (FGFR4), platelet-derived growth factor receptor-beta (PDG-FRB), and fms-related tyrosine kinase-4 (FLT4). The genes and gene products associated with familial hemangiomas may be involved somatically in the more common sporadic cases
— id: 57079, year: 1999, vol: 82, page: 77, stat: Journal Article,

Loss of heterozygosity of 5q in sporadic hemangiomas suggests that somatic mutations are involved with hemangioma development
Walter, JW; Berg, JN; Evans, M; Reinhardt, D; Thisanayagam, U; Blei, F; Diamond, A; Waner, M; Marchuk, DA; Porteous, MEM
1999 OCT ;65(4):A328-A328, American journal of human genetics
— id: 53828, year: 1999, vol: 65, page: A328, stat: Journal Article,

Successful multimodal therapy for kaposiform hemangioendothelioma complicated by Kasabach-Merritt phenomenon: case report and review of the literature [see comments]
Blei F; Karp N; Rofsky N; Rosen R; Greco MA
1998 Jul-Aug;15(4):295-305, Pediatric hematology & oncology
We present the management challenge provided by a patient with kaposiform hemangioendothelioma associated with Kasabach-Merritt phenomenon. A female child presented at 14 months of age with an ecchymotic swelling of her right upper arm and axilla. Subsequently, she developed profound thrombocytopenia and hypofibrinogenemia (Kasabach-Merritt phenomenon). Biopsy of the lesion revealed kaposiform hemangioendothelioma, which has been reported as the predominant pathologic diagnosis associated with Kasabach-Merritt phenomenon. To achieve involution of the lesion and preserve function of the arm, the following interventions were involved: embolization, systemic interferon, cyclophosphamide, epsilon aminocaproic acid, and compression therapy. The clinical management of this patient was formidable until we arrived at the proper combination of therapies. Multimodal intervention may be required to manage fastidious hemangioendotheliomas of childhood, achieve clinical improvement, and prevent further morbidity
— id: 7507, year: 1998, vol: 15, page: 295, stat: Journal Article,

Familial segregation of hemangiomas and vascular malformations as an autosomal dominant trait [see comments] [published erratum appears in Arch Dermatol 1998 Nov;134(11):1425]
Blei F; Walter J; Orlow SJ; Marchuk DA
1998 Jun;134(6):718-722, Archives of dermatology
BACKGROUND: The pathogenesis of infantile hemangiomas is not yet understood. Growth factors and hormonal and mechanical influences have been thought to affect the focal abnormal growth of endothelial cells in these lesions. However, these influences may represent secondary responses to an underlying primary molecular event leading to the development of hemangiomas. OBSERVATIONS: We report the rare familial occurrence of hemangiomas and/or vascular malformations in 6 kindreds, suggesting autosomal dominant inheritance. In these families, multiple generations (2-4) were affected by hemangiomas or vascular malformations. In contrast to the generally accepted female-male ratio of 3:1 to 4:1 associated with sporadic hemangiomas, the families with hemangiomas in our study demonstrated a 2:1 ratio. Additionally, vascular malformations and hemangiomas were present in different members of the same family. The vascular lesions appeared to be transmitted in an autosomal dominant fashion with moderate to high penetrance. CONCLUSIONS: We have identified 6 families demonstrating autosomal dominant segregation of childhood hemangiomas. Additionally, family members with vascular malformations were identified in these kindreds. Physicians caring for children with hemangiomas and vascular malformations should include in their medical histories inquiries about vascular lesions in other family members, even when obvious lesions are not present in the parents. The identification of the mutation(s) underlying vascular lesions will provide insight into the pathogenesis of these familial hemangiomas and, potentially, common sporadic hemangiomas. In addition, such research would shed light on the regulation of angiogenic processes during development
— id: 7506, year: 1998, vol: 134, page: 718, stat: Journal Article,

Neurotoxicity of interferon alfa in children treated for hemangiomas - Reply
Blei, F
1998 DEC ;39(6):1037-1038, Journal of the American Academy of Dermatology
— id: 53634, year: 1998, vol: 39, page: 1037, stat: Journal Article,

The response of parotid hemangiomas to the use of systemic interferon alfa-2a or corticosteroids
Blei F; Isakoff M; Deb G
1997 Aug;123(8):841-844, Archives of otolaryngology, head & neck surgery
OBJECTIVE: To evaluate medical treatment for hemangiomas involving the parotid area with or without other areas of involvement. DESIGN: Retrospective analysis of pediatric patients treated medically for proliferative hemangiomas of the parotid region with or without hemangiomas in other regions. Indications for treatment included respiratory symptoms relating to hemangiomas of the upper airway, difficulty feeding, rapid rate of growth of the hemangioma, and deformity or obstruction of the ear canal. SETTING: New York University Multidisciplinary Vascular Anomaly Conference, New York, NY, and the Pediatric Oncology Department of Ospedale Pediatrico Bambino Gesu, Rome, Italy. PATIENTS: Thirteen patients with proliferative hemangiomas in the parotid area were treated medically to inhibit growth and enhance involution of the hemangioma. INTERVENTION: Six patients were treated with corticosteroids alone (2-4 mg/kg daily). Two patients were treated with corticosteroids (2-4 mg/kg daily) followed by interferon alfa-2a (3 million U/m2 daily) because of a failure to respond to corticosteroid therapy. One patient was treated with interferon alfa-2a alone (3 million U/m2 daily). Four patients were initially treated with interferon alfa-2a, then treated with corticosteroids. One of these patients required intralesional corticosteroid therapy for a massively enlarged lip and is therefore included in this group. The other patient was given oral corticosteroids for unknown reasons at another institution. In the remaining 2 patients, there was no response to the use of interferon alfa-2a. MAIN OUTCOME MEASURES: The size, bulk, and symptoms relating to the hemangiomas of the patients were assessed. RESULTS: None of the patients had a significant improvement of the lesions of the parotid hemangiomas. In contrast, for those patients with clinical symptoms due to hemangiomas elsewhere or with cutaneous involvement typical of hemangiomas, the symptoms improved with either of the above therapies, and the cutaneous areas demonstrated signs of involution. CONCLUSIONS: The results in the 13 patients in this article demonstrate that hemangiomas in certain anatomic sites, such as the parotid area, may be more resistant to therapy with corticosteroids or interferon alfa-2a. Differences in drug metabolism, caliber of blood vessels, and/or blood flow in the parotid gland may account for this observation
— id: 7116, year: 1997, vol: 123, page: 841, stat: Journal Article,

Multimodal management of diffuse neonatal hemangiomatosis
Blei F; Orlow SJ; Geronemus R
1997 Dec;37(6):1019-1021, Journal of the American Academy of Dermatology
— id: 57104, year: 1997, vol: 37, page: 1019, stat: Journal Article,

Increased risk of symptomatic hemangiomas of the airway in association with cutaneous hemangiomas in a "beard" distribution [see comments]
Orlow SJ; Isakoff MS; Blei F
1997 Oct;131(4):643-646, Journal of pediatrics
We evaluated the frequency of an association of cutaneous cervicofacial hemangiomas in a 'beard' distribution (including the preauricular areas, chin, anterior neck, and lower lip) with symptomatic hemangiomas of the upper airway or subglottic areas. Of 529 patients seen, 187 were pediatric patients with hemangiomas of the head and neck. Sixteen of the 187 patients (8.5%) had cutaneous lesions with a beard distribution, with a score of 4 or greater. Ten of these 16 (63%) patients had some degree of symptomatic airway involvement, and four of the 10 (40%) required tracheotomy. The presence of cutaneous hemangiomas in a beard distribution should alert the evaluating physician to the potential association of upper airway or subglottic involvement
— id: 12218, year: 1997, vol: 131, page: 643, stat: Journal Article,

Description of a novel hereditary form of capillary hemangioma and genetic mapping of predisposing chromosomal loci
Walter, JW; Blei, FM; Marchuk, DA
1997 OCT ;61(4):A299-A299, American journal of human genetics
— id: 53610, year: 1997, vol: 61, page: A299, stat: Journal Article,

Three globin gene abnormalities and a red cell enzymopathy in one patient
Blei, F; HadziNesic, I; Nardi, M
1995 NOV 15 ;86(10):2559-2559, Blood
— id: 53123, year: 1995, vol: 86, page: 2559, stat: Journal Article,

Levels of thrombomodulin, interleukin-1 beta, and interleukin-2 receptor alpha in sickle cell disease
Blei, F; Slobodkina, O; Chasalow, F; Guarini, L
1995 NOV 15 ;86(10):2558-2558, Blood
— id: 53122, year: 1995, vol: 86, page: 2558, stat: Journal Article,

ELEVATED LEVELS OF CIRCULATING MOLECULES OF POTENTIAL ENDOTHELIAL ORIGIN IN SICKLE-CELL DISEASE
BLEI, F; FANCHER, T; GUARINI, L
1994 NOV 15 ;84(10):A409-A409, Blood
— id: 52286, year: 1994, vol: 84, page: A409, stat: Journal Article,

LEVELS OF CIRCULATING VASCULAR CELL-ADHESION MOLECULE-1 (CVCAM-1) AND INTERCELLULAR-ADHESION MOLECULE-1 (CICAM-1) AND E-SELECTIN (CE-SELECTIN) IN PATIENTS WITH HEMANGIOMAS AND VASCULAR MALFORMATIONS
BLEI, F; FANCHER, T; GUARINI, L
1994 NOV 15 ;84(10):A563-A563, Blood
— id: 52290, year: 1994, vol: 84, page: A563, stat: Journal Article,

Interferon alfa-2a therapy for extensive perianal and lower extremity hemangioma
Blei F; Orlow SJ; Geronemus RG
1993 Jul;29(1):98-99, Journal of the American Academy of Dermatology
— id: 8235, year: 1993, vol: 29, page: 98, stat: Journal Article,

Supraumbilical midabdominal raphe, sternal atresia, and hemangioma in an infant: response of hemangioma to laser and interferon alfa-2a [see comments]
Blei F; Orlow SJ; Geronemus RG
1993 Mar;10(1):71-76, Pediatric dermatology
We cared for an infant girl with the clinical constellation of supraumbilical midabdominal raphe, sternal atresia, and cutaneous facial and upper trunk hemangioma. This is the first report of this clinical association in the dermatologic literature. The vascular component of the disorder responded to flashlamp-pumped pulsed dye laser therapy and to systemic interferon alfa-2a (Roferon-A)
— id: 9178, year: 1993, vol: 10, page: 71, stat: Journal Article,

Yersinia enterocolitica bacteremia in a chronically transfused patient with sickle cell anemia. Case report and review of the literature
Blei F; Puder DR
1993 Nov;15(4):430-434, American journal of pediatric hematology-oncology
PURPOSE: Yersinia enterocolitica sepsis is rarely encountered in patients without an underlying susceptibility and is most frequently reported in iron-overloaded patients. This is thought to be related to the unusual utilization of iron by this microorganism. We report a case of Y. enterocolitica bacteremia in a chronically transfused adolescent with sickle cell anemia. This type of serious infection in sickle cell disease is previously unreported. A description of the case and the relationship between Y. enterocolitica and iron is discussed. A review of the literature is presented. RESULTS: Y. enterocolitica can cause a severe septicemia, and increased virulence of this organism has been shown to correlate with increased iron burden and/or use of the chelator deferoxamine. It may also occur as a consequence of a contaminated blood transfusion. CONCLUSIONS: We believe our case demonstrates that Y. enterocolitica should be considered a possible pathogen in febrile chronically transfused patients with sickle cell disease. Broad antibiotic coverage should be initiated and deferoxamine discontinued pending results of cultures
— id: 6328, year: 1993, vol: 15, page: 430, stat: Journal Article,

Mechanism of action of angiostatic steroids: suppression of plasminogen activator activity via stimulation of plasminogen activator inhibitor synthesis
Blei F; Wilson EL; Mignatti P; Rifkin DB
1993 Jun;155(3):568-578, Journal of cellular physiology
Recently, a novel class of angiostatic steroids which block angiogenesis in several systems has been described. Since the elaboration of proteases is believed to be an important component of angiogenesis, we tested whether these steroids blocked the fibrinolytic response of endothelial cells to the angiogenic protein, basic fibroblast growth factor [bFGF]). Cultured bovine aortic endothelial (BAE) cells were incubated with bFGF and/or medroxyprogesterone acetate (MPA), an angiostatic steroid which has been shown to inhibit vascularization, collagenolysis, and tumor growth. When bFGF (3 ng/ml) was added to confluent monolayers of BAE cells, plasminogen activator (PA) activity in the medium was increased threefold. In contrast, MPA at 10(-6) M, 10(-7) M, 10(-8) M, and 10(-9) M decreased PA levels in the medium by 83%, 83%, 75%, and 39%, respectively. The stimulation of PA levels in BAE cells by bFGF (3 ng/ml) was abrogated by the presence of 10(-6) M MPA. This decrease in PA activity was found to be mediated by a significant increase in plasminogen activator inhibitor type-1 (PAI-1) production. MPA, therefore, negated one of the important enzymatic activities associated with the angiogenic process. In contrast to the decreased levels of secreted PA in cultures exposed simultaneously to MPA and bFGF, cell-associated PA levels remained high, consistent with earlier observations indicating that PAI-1 does not inhibit cell-associated PA. Thus, angiostatic steroids may exert their inhibitory effects on angiogenesis by increasing the synthesis of PAI-1. This, in turn, inhibits PA activity and, therefore, plasmin generation, which is essential for the invasive aspect of angiogenesis
— id: 8234, year: 1993, vol: 155, page: 568, stat: Journal Article,

MODIFICATION OF TOXICITY OF INTERFERON-ALFA-2A FOR TREATMENT OF HEMANGIOMAS OF INFANCY
BLEI, F
1993 NOV 15 ;82(10):A581-A581, Blood
— id: 52149, year: 1993, vol: 82, page: A581, stat: Journal Article,

ELEVATED LEVELS OF CIRCULATING INTERCELLULAR-ADHESION MOLECULE-1 (CICAM-1) IN SICKLE-CELL DISEASE
BLEI, F; BARNES, K; GUARINI, L
1993 NOV 15 ;82(10):A354-A354, Blood
— id: 52145, year: 1993, vol: 82, page: A354, stat: Journal Article,

HEMANGIOMAS ASSOCIATED WITH MAJOR MORBIDITY SUCCESSFULLY TREATED WITH INTERFERON ALFA-2A THERAPY
BLEI, F; GERONEMUS, RG
1993 APR ;41(2):A314-A314, Clinical research
— id: 54277, year: 1993, vol: 41, page: A314, stat: Journal Article,

ANGIOSTATIC STEROIDS INHIBIT ENDOTHELIAL-CELL PLASMINOGEN-ACTIVATOR ACTIVITY
BLEI, F; WILSON, EL; RIFKIN, DB
1991 APR ;29(4):A137-A137, Pediatric research
— id: 51662, year: 1991, vol: 29, page: A137, stat: Journal Article,

Prothrombin expression in the adult and fetal rabbit liver
Karpatkin M; Blei F; Hurlet A; Greco A; Tang Z
1991 Sep;30(3):266-269, Pediatric research
Plasma prothrombin levels in newborn humans are lower than in adults. The same is true of many newborn and fetal mammals, including the rabbit. To determine if the lower levels are due to less expression of the protein, we have compared mRNA for prothrombin in fetal and adult rabbit liver. Northern blots were hybridized with a cDNA for rabbit prothrombin revealing a single mRNA of approximately 2 kb in both adult and fetal animals. mRNA specific for prothrombin was quantitated by slot blotting of RNA prepared from adults and fetuses aged 21 d to term (31 d). Prothrombin-specific mRNA in fetuses was greater than 50% of that in adults even when the fetal plasma prothrombin was only 15% of the adult level. This suggests that low plasma levels in the fetuses are not the result of less transcription. Examination of liver sections revealed that the predominant tissue in the fetus is hematopoietic, not hepatic. In the youngest fetuses, less than 20% of the liver consisted of hepatocytes, yet these fetuses expressed more than 50% of the adult level of prothrombin-specific mRNA. Thus, transcription of prothrombin mRNA may be proceeding at a greater rate in the fetal hepatocyte than in the adult, or hematopoietic cells may be expressing the protein. We conclude that in fetal rabbit liver, prothrombin is expressed at a high level relative to the hepatocyte content and that the cause of the low plasma levels is posttranscriptional
— id: 57467, year: 1991, vol: 30, page: 266, stat: Journal Article,

Cloning and partial sequence of a cDNA for rabbit prothrombin
Karpatkin M; Tang ZC; Meer J; Blei F; Samuels HH
1991 Jun 15;62(6):757-763, Thrombosis research
A 1466 base pair cDNA for rabbit prothrombin has been isolated and partially sequenced. The deduced amino acid sequence shows considerable homology with the sequences of human and bovine prothrombin. The cDNA extends from the equivalent of nucleotide 516 in the bovine sequence through the coding region and 99 nucleotides in the 3' non-coding region
— id: 13995, year: 1991, vol: 62, page: 757, stat: Journal Article,

PROTHROMBIN SYNTHESIS IN THE ADULT AND FETUS - STUDIES IN A RABBIT MODEL
KARPATKIN, M; TANG, Z; PUGLISI, V; HURLET, A; BLEI, F
1991 APR ;29(4):A143-A143, Pediatric research
— id: 51663, year: 1991, vol: 29, page: A143, stat: Journal Article,

Chelation therapy and cardiac status in older patients with thalassemia major
Lerner N; Blei F; Bierman F; Johnson L; Piomelli S
1990 Spring;12(1):56-60, American journal of pediatric hematology-oncology
Cardiac dysfunction is the most common cause of death in patients with homozygous beta-thalassemia. We studied a group of 10 older patients (mean age 17.5 years) with and without preexisting cardiac dysfunction who had begun chelation therapy on the average of 10 years after regular transfusions were initiated. Over the 4-year study period, two patients were noncompliant with deferoxamine therapy. Their clinical status and cardiac function deteriorated, and both died with evidence of arrhythmia and congestive heart failure. The remaining eight patients were compliant. Despite a drop in mean serum ferritin from 3,814 +/- 577 (SE) ng/ml to 1,056 +/- 146 ng/ml (p less than 0.01), two patients with preexisting cardiac problems and one patient without preexisting heart disease developed further abnormalities. Of the three patients whose status declined, one ultimately improved with alternative chelation therapy. These data suggest that for a few older patients, improvement or stabilization of cardiac status may not be achieved with improved compliance and reduced serum ferritin levels. For these patients, new approaches appear to be warranted. On the other hand, we have demonstrated that in most cases, older patients who began chelation therapy years after transfusions began have benefited from compliance with standard subcutaneous deferoxamine regimens
— id: 19447, year: 1990, vol: 12, page: 56, stat: Journal Article,

An isozyme of hexokinase specific for the human red blood cell (HKR)
Murakami K; Blei F; Tilton W; Seaman C; Piomelli S
1990 Feb 1;75(3):770-775, Blood
The hexokinase (HK) of the human red blood cell (RBC) was separated into two distinct major isozymes by fast protein liquid chromatography using a linear salt gradient on a MonoQ column. The first isozyme (HKI) eluted as a sharp peak at the same position as HKI of human liver. The second isozyme eluted between HKI and HKII of human white blood cells, and it appeared to be unique to the RBC (it was designated HKR). From a gel filtration column, HKR eluted before HKI, suggesting that it was larger than HKI by several kilodaltons. In a mitochondria-enriched fraction from human reticulocytes, no HKR was found; thus, HKR was not a mitochondrial enzyme. Despite these differences in chromatographic behavior, size, and mitochondrial binding, both forms behaved kinetically as HKI. RBC from normal blood contained HKI and HKR at an equal activity, but in reticulocyte-rich RBC, HKR dominated. When RBC of increasing age was separated by buoyant density ultracentrifugation, the total HK activity decayed in a biphasic manner, with half-lives respectively of approximately 15 and approximately 51 days. When isolated by MonoQ column from each age-separated fraction, HKR was the major form in the youngest RBC, and decreased rapidly with cell age, with a t 1/2 of approximately 10 days, representing a negligible activity in the oldest RBC. Instead, HKI was relatively stable through the entire life span of the RBC, with a t 1/2 of approximately 66 days. Thus, HKR appears to be an RBC-specific isozyme that is predominant in the reticulocyte and is then rapidly degraded. During maturation of the RBC, the fast decay of HKR contributes to the early sharp decline of HK activity and the slow decay of HKI to the later gradual decline
— id: 19446, year: 1990, vol: 75, page: 770, stat: Journal Article,

Planning an exchange transfusion in patients with sickle cell syndromes
Piomelli S; Seaman C; Ackerman K; Yu E; Blei F
1990 Fall;12(3):268-276, American journal of pediatric hematology-oncology
Partial exchange transfusions are performed in sickle cell patients for a variety of reasons. An algorithm to plan a nonautomated exchange in patients with sickle cell syndromes was developed and validated by a study of 40 such procedures. Formulas that can be used to explore alternatives, by assessing at any point during the exchange the current concentration of sickleable cells and the hematocrit, were devised: a computer program in BASIC is available for maximum versatility. The two most important determinants of the exchange are the patient's initial hematocrit and the desired final concentration of sickleable cells; the rate and type of exchange (continuous or discontinuous) are not important. The final hematocrit depends on the type of blood product used. An exchange can be performed with packed red blood cells (PRBC), whole blood (or its equivalent, PRBC reconstituted with albumin), or it can be started with PRBC and continued with whole blood. Whole blood decreases the concentration of sickeleable cells rapidly and increases the hematocrit slowly; it does not markedly increase the viscosity. PRBCs decrease the concentration of sickleable cells more slowly and increase the hematocrit faster; thus, they may increase the blood viscosity to dangerous levels
— id: 19448, year: 1990, vol: 12, page: 268, stat: Journal Article,

Growth factor control of extracellular proteolysis
Rifkin DB; Moscatelli D; Bizik J; Quarto N; Blei F; Dennis P; Flaumenhaft R; Mignatti P
1990 Dec 2;32(3):313-318, Cell differentiation & development
The involvement of proteases and growth factors in angiogenesis is complex. The angiogenic factor basic fibroblast growth factor (bFGF) induces increased synthesis of both plasminogen activator and collagenase in endothelial cells. In addition, bFGF increases the number of plasminogen activator receptors on the cell surface. Increased production of plasmin may be responsible for the release of soluble complexes of heparan sulfate-bFGF which may be the active form of bFGF. The activity of a negative regulator of angiogenesis, transforming growth factor beta (TGF-beta), is also regulated by proteases since the released latent form of TGF-beta is activated by a surface proteolytic assembly plasminogen activator and plasmin. Since TGF-beta induces an inhibitor of plasminogen activator, the activation reaction is self-regulatory
— id: 14245, year: 1990, vol: 32, page: 313, stat: Journal Article,

Giant marker chromosome in Fanconi's anemia transforming into erythroleukemia in an adult
Rotzak R; Kaplinsky N; Chaki R; Blei F; Berkowitz M; Goldman B; Frankl O
1982 ;67(3):214-216, Acta haematologica
— id: 19449, year: 1982, vol: 67, page: 214, stat: Journal Article,