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Find video protocols related to scientific articles indexed in Pubmed.
Successful treatment of post-transplant thrombocytopenia with romiplostim in a pediatric patient with X-linked chronic granulomatous disease.
Pediatr Transplant
PUBLISHED: 08-13-2014
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Thrombocytopenia is a frequent complication following HSCT in pediatric patients. Romiplostim is a TPO receptor agonist that has been utilized successfully in the treatment of pediatric patients with immune thrombocytopenia. We describe a three-yr-old male with X-linked CGD treated with an unrelated donor bone marrow transplant. His course was complicated by the development of symptomatic thrombocytopenia. He was started on romiplostim with prompt improvement in his thrombocytopenia. We found the use of romiplostim to be an effective and safe alternative to the potential complications as well as morbidity and mortality associated with the use of immunosuppressive agents such as corticosteroids.
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Use of Factor XIII (FXIII) concentrate in patients with congenital FXIII deficiency undergoing surgical procedures.
Transfusion
PUBLISHED: 02-28-2014
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Patients with congenital Factor XIII (FXIII) deficiency have impaired fibrin stabilization and are at high risk for surgical bleeding. Data regarding the use of FXIII concentrates before and during surgery are lacking. The objective of this study was to report the use of plasma-derived FXIII concentrate (Corifact in the United States; Fibrogammin P in other countries) in patients with congenital FXIII deficiency undergoing surgical procedures.
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Effects of hematopoietic stem cell transplantation on acyl-CoA oxidase deficiency: a sibling comparison study.
J. Inherit. Metab. Dis.
PUBLISHED: 02-17-2014
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Acyl-CoA oxidase (ACOX1) deficiency is a rare disorder of peroxisomal very-long chain fatty acid oxidation. No reports detailing attempted treatment, longitudinal imaging, or neuropathology exist. We describe the natural history of clinical symptoms and brain imaging in two siblings with ACOX1 deficiency, including the younger sibling's response to allogeneic unrelated donor hematopoietic stem cell transplantation (HSCT).
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Thrombopoietic agents for the treatment of persistent and chronic immune thrombocytopenia in children.
J. Pediatr.
PUBLISHED: 01-28-2014
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To determine the safety, tolerability, or efficacy of 2 licensed thrombopoietic agents in children with persistent and chronic immune thrombocytopenia (ITP).
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Tissue factor inflammatory response regulated by promoter genotype and p38 MAPK in neonatal vs. adult microvascular endothelial cells.
Inflamm. Res.
PUBLISHED: 01-03-2014
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Variable tissue factor (TF) expression by human microvascular endothelial cells (HMVEC) may be regulated by two promoter haplotypes, distinguished by an 18-basepair deletion (D) or insertion (I) at -1,208. We sought to determine the relationship between these haplotypes and interleukin-1? (IL-1?)-induced TF expression in neonatal versus adult HMVEC.
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Wiskott-Aldrich syndrome: diagnosis, current management, and emerging treatments.
Appl Clin Genet
PUBLISHED: 01-01-2014
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Wiskott-Aldrich syndrome (WAS) is a rare X-linked primary immunodeficiency disorder characterized by the triad of eczema, thrombocytopenia, and severe and often recurrent infections. Despite the rarity of this disorder, our understanding of the molecular and cellular pathogenesis of WAS has continued to increase. Advances in the use of diagnostic tools, the provision of supportive care, and improvements in allogeneic hematopoietic stem cell transplantation have significantly reduced the morbidity and mortality associated with this disorder. Exciting advancements in the care of patients with WAS have also occurred, including the successful application of autologous gene-modified hematopoietic stem cell transplantation.
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Successful autologous cord blood transplantation in a child with acquired severe aplastic anemia.
Pediatr Transplant
PUBLISHED: 01-25-2013
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Over 400 cases of pediatric SAA occur annually in the United States. A growing number of children with SAA may have had their stem cells harvested through cord blood collection. We describe a nine-yr-old male with SAA treated successfully with an autologous cord blood transplant following immunoablative chemotherapy. With the increasing number of people cryopreserving autologous cord blood, the use of autologous cord blood in the treatment of SAA might be considered as initial therapy. This case serves to discuss approaches to preparative therapy as well as the potential complications in this growing cohort of patients.
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Conditional knockout of integrin ?2?1 in murine megakaryocytes leads to reduced mean platelet volume.
PLoS ONE
PUBLISHED: 01-24-2013
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We have engineered a transgenic mouse on a C57BL/6 background that bears a floxed Itga2 gene. The crossing of this mouse strain to transgenic mice expressing Cre recombinase driven by the megakaryocyte (MK)-specific Pf4 promoter permits the conditional knockout of Itga2 in the MK/platelet lineage. Mice lacking MK ?2?1 develop normally, are fertile, and like their systemic ?2?1 knockout counterparts, exhibit defective adhesion to and aggregation induced by soluble type I collagen and a delayed onset to low dose fibrillar collagen-induced aggregation, results consistent with blockade or loss of platelet ?2?1. At the same time, we observed a significant reduction in mean platelet volume, which is consistent with the reported role of ?2?1 in MK maturation and proplatelet formation in vivo. This transgenic mouse strain bearing a floxed Itga2 gene will prove valuable to distinguish in vivo the temporal and spatial contributions of ?2 integrin in selected cell types.
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Platelet adhesion to decorin but not collagen I correlates with the integrin ?2 dimorphism E534K, the basis of the human platelet alloantigen (HPA)-5 system.
Haematologica
PUBLISHED: 12-01-2011
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A single nucleotide polymorphism in the integrin ?2 gene ITGA2 (rs1801106; G1600A) creates the non-conservative amino acid substitution E534K, the basis of the human platelet alloantigen system HPA-5. Yet HPA-5 alleles do not influence binding of ?2?1 to its primary ligand collagen I, and the effect of HPA-5 on platelet function has not been determined. We used a direct platelet adhesion assay to evaluate whether differential inheritance of HPA-5 alleles influences platelet adhesion to collagen I or an alternative ligand, decorin. Platelets from donors bearing one or more minor allele HPA-5b showed attenuated adhesion to purified decorin but not collagen I. Adhesion to decorin was significantly inhibited by human alloantibodies specific for HPA-5a but not by the collagen I sequence GFOGER or ?2-specific inhibitory monoclonal antibodies. The minor allele 534K attenuates platelet adhesion to decorin but not collagen I, providing the first evidence of a functional effect of HPA-5 alleles.
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A patient with familial bone marrow failure and an inversion of chromosome 8.
J. Pediatr. Hematol. Oncol.
PUBLISHED: 11-02-2011
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Familial bone marrow failure has been associated with a variety of chromosomal aberrations. Chromosome 8 abnormalities have been described in association with neoplastic and hematologic disorders; however, to our knowledge, inversion of the long arm of chromosome 8 has not been described in the context of familial bone marrow failure. We describe a 9-year-old female with familial bone marrow failure and an inversion of chromosome 8 [inv (8) (q22, q24.3)]. Given the importance of considering the genetic determinants of familial bone marrow failure, the potential role of chromosome 8 abnormalities in the development of marrow failure is discussed.
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Mean platelet volume and integrin alleles correlate with levels of integrins ?(IIb)?(3) and ?(2)?(1) in acute coronary syndrome patients and normal subjects.
Arterioscler. Thromb. Vasc. Biol.
PUBLISHED: 10-20-2011
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The interindividual variation in platelet ?(2)?(1) exceeds a 2-fold variance in platelet ?(IIb)?(3) level. Our objective was to parse the contribution of mean platelet volume (MPV) and integrin gene alleles to this variation in large cohorts of patients with acute coronary syndrome (ACS) and normal subjects.
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Inflammatory polyps following successful HLA-matched cord blood transplantation in a patient with X-linked lymphoproliferative syndrome.
Pediatr Transplant
PUBLISHED: 07-08-2011
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Gastrointestinal complications following HSCT are numerous and include a variety of issues resulting in hepatic, biliary, pancreatic, and intestinal compromise. In the context of an underlying state of immune dysregulation, novel complications may arise including autoimmunity. To our knowledge, this is the first report of a patient with XLP who was successfully treated with HSCT using an HLA-matched unrelated cord blood unit that was complicated by the development of inflammatory polyps of the colon. Given the underlying diagnosis of XLP and its associated immune dysregulation, the challenge of understanding unique gastrointestinal manifestations of autoimmunity following HSCT is discussed.
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Monozygotic twin pair showing discordant phenotype for X-linked thrombocytopenia and Wiskott-Aldrich syndrome: a role for epigenetics?
J. Clin. Immunol.
PUBLISHED: 05-05-2011
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Despite our increasing characterization of the molecular basis for many primary immunodeficiency states, significant heterogeneity in clinical and immunological phenotype exists. Epigenetic alterations have been implicated in the pathogenesis of immune dysregulation and may provide a unique paradigm to help us understand the phenotypic heterogeneity in primary immunodeficiency. The occurrence of X-linked thrombocytopenia (XLT) and Wiskott-Aldrich syndrome (WAS) in monozygotic twins is a rare occurrence which allows for the exploration of epigenetic alterations and associated phenotypic heterogeneity. We describe a pair of monozygotic twin brothers with a missense mutation in the WAS gene consistent with reduced expression of the WAS protein, a XLT phenotype, and a good prognosis. Despite this genotype and anticipated mild phenotype in both twins, a discordant phenotype has evolved in which one twin demonstrates asymptomatic thrombocytopenia and the other symptomatic thrombocytopenia, infectious complications, and autoimmunity. Characterization of the potential epigenetic contribution to the spectrum of XLT and WAS is described and the implications of these findings are discussed.
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A randomized, double-blind study of romiplostim to determine its safety and efficacy in children with immune thrombocytopenia.
Blood
PUBLISHED: 04-18-2011
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Romiplostim, a thrombopoietin-mimetic peptibody, increases and maintains platelet counts in adults with immune thrombocytopenia (ITP). In this first study of a thrombopoietic agent in children, patients with ITP of ? 6 months duration were stratified by age 1:2:2 (12 months-< 3 years; 3-< 12 years; 12-< 18 years). Children received subcutaneous injections of romiplostim (n = 17) or placebo (n = 5) weekly for 12 weeks, with dose adjustments to maintain platelet counts between 50 × 10(9)/L and 250 × 10(9)/L. A platelet count ? 50 × 10(9)/L for 2 consecutive weeks was achieved by 15/17 (88%) patients in the romiplostim group and no patients in the placebo group (P = .0008). Platelet counts ? 50 × 10(9)/L were maintained for a median of 7 (range, 0-11) weeks in romiplostim patients and 0 (0-0) weeks in placebo patients (P = .0019). The median weekly dose of romiplostim at 12 weeks was 5 ?g/kg. Fourteen responders received romiplostim for 4 additional weeks for assessment of pharmacokinetics. No patients discontinued the study. There were no treatment-related, serious adverse events. The most commonly reported adverse events in children, as in adults, were headache and epistaxis. In this short-term study, romiplostim increased platelet counts in 88% of children with ITP and was well-tolerated and apparently safe. The trial was registered with http://www.clinicaltrials.gov as NCT00515203.
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Response to steroids predicts response to rituximab in pediatric chronic immune thrombocytopenia.
Pediatr Blood Cancer
PUBLISHED: 02-18-2011
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Treatment choice in pediatric immune thrombocytopenia (ITP) is arbitrary, because few studies are powered to identify predictors of therapy response. Increasingly, rituximab is becoming a treatment of choice in those refractory to other therapies.
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FondaKIDS: a prospective pharmacokinetic and safety study of fondaparinux in children between 1 and 18 years of age.
Pediatr Blood Cancer
PUBLISHED: 02-11-2011
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The incidence of thromboembolic disease is increasing in children. New anticoagulants have been licensed in adults and need to be studied in children. This report describes the first prospective study of fondaparinux in children.
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Unrelated hematopoietic stem cell transplantation in a patient with congenital dyserythropoietic anemia and iron overload.
Pediatr Transplant
PUBLISHED: 11-26-2010
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CDA is a heterogeneous group of disorders that result in morphologically abnormal erythroid maturation and ineffective erythropoiesis. Curative therapy for CDA focuses on the use of HSCT using fully matched sibling donors. This is the first report of a Type II CDA patient with severe iron overload who was successfully treated with HSCT using a HLA-matched unrelated donor after aggressive chelation therapy. Given the challenges of HSCT in any patient with CDA and severe iron overload, the role of novel approaches to iron chelation and HSCT is discussed.
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The genetics of normal platelet reactivity.
Blood
PUBLISHED: 07-07-2010
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Genetic and environmental factors contribute to a substantial variation in platelet function seen among normal persons. Candidate gene association studies represent a valiant effort to define the genetic component in an era where genetic tools were limited, but the single nucleotide polymorphisms identified in those studies need to be validated by more objective, comprehensive approaches, such as genome-wide association studies (GWASs) of quantitative functional traits in much larger cohorts of more carefully selected normal subjects. During the past year, platelet count and mean platelet volume, which indirectly affect platelet function, were the subjects of GWAS. The majority of the GWAS signals were located to noncoding regions, a consistent outcome of all GWAS to date, suggesting a major role for mechanisms that alter phenotype at the level of transcription or posttranscriptional modifications. Of 15 quantitative trait loci associated with mean platelet volume and platelet count, one located at 12q24 is also a risk locus for coronary artery disease. In most cases, the effect sizes of individual quantitative trait loci are admittedly small, but the results of these studies have led to new insight into regulators of hematopoiesis and megakaryopoiesis that would otherwise be unapparent and difficult to define.
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Living Profiles: design of a health media platform for teens with special healthcare needs.
J Biomed Inform
PUBLISHED: 03-02-2010
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Living Profiles is a health media platform in development that aggregates multiple data flows to help teens with special healthcare needs (SHCN), particularly with regard to self-management and independence. A teen-oriented personal health record (PHR) incorporates typical teen behaviors and attitudes about health and wellness, encompasses how teens perceive and convey quality of life, and aligns with data related to their chronic medical condition. We have conceived a secure personalized user interface called the Quality of Life Timeline, which will assist with the transition from pediatric care to an adult provider through modules that include a mood meter, reminder device, and teleport medicine. With this personalized PHR, teens with SHCN can better understand their condition and its effects on daily activities and life goals and vice versa; additionally, use of this PHR allows for better information sharing and communication between providers and patients. The use of a teen-oriented tool such as Living Profiles can impact teens overall quality of life and disease self-management, important attributes for a successful transition program.
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Enhanced binding of poly(ADP-ribose)polymerase-1 and Ku80/70 to the ITGA2 promoter via an extended cytosine-adenosine repeat.
PLoS ONE
PUBLISHED: 01-15-2010
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We have identified a cytosine-adenosine (CA) repeat length polymorphism in the 5-regulatory region of the human integrin alpha2 gene ITGA2 that begins at -605. Our objective was to establish the contribution of this polymorphism to the regulation of integrin alpha2beta1 expression, which is known to vary several-fold among normal individuals, and to investigate the underlying mechanism(s).
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The low-frequency isoform of platelet glycoprotein VIb attenuates ligand-mediated signal transduction but not receptor expression or ligand binding.
Blood
PUBLISHED: 05-22-2009
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The 2 most common haplotypes of human GP6, GP6a and GP6b, generate the allelic isoforms glycoprotein VI (GPVI)a and GPVIb that differ by 5 amino acids: S219P, K237E, and T249A in the ectodomains, and Q317L and H322N in the cytoplasmic domain. By quantitative Western blot, we found no association between GP6 genotype and total platelet GPVI content among 132 normal subjects. When expressed as soluble products or as membrane-associated receptors, GPVIa and GPVIb have identical affinities for type I collagen, collagen-related peptide, or convulxin. However, the cytoplasmic domain substitutions in GPVIb have a significant effect on GPVI-dependent subcellular associations and ligand-induced signal transduction. L317 increases binding to calmodulin, whereas N322 attenuates binding to Fyn/Lyn. Consistent with the latter finding, convulxin-induced Syk phosphorylation is significantly attenuated in Dami cells stably transfected with GPVIb, relative to GPVIa. This represents direct evidence that haplotype-related GPVI functional differences are inherent in the cytoplasmic domain substitutions, whereby GPVIb binds less strongly to Fyn/Lyn and attenuates the rate and extent of Syk phosphorylation. These allelic differences in GP6a and GP6b explain functional differences in the respective isoforms, but the molecular basis for the several-fold range in GPVI levels of human platelets remains to be determined.
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Pathogenesis of chronic immune thrombocytopenia: increased platelet destruction and/or decreased platelet production.
Br. J. Haematol.
PUBLISHED: 05-14-2009
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Chronic immune thrombocytopenia (ITP) is a haematological disorder in which patients predominantly develop skin and mucosal bleeding. Early studies suggested ITP was primarily due to immune-mediated peripheral platelet destruction. However, increasing evidence indicates that an additional component of this disorder is immune-mediated decreased platelet production that cannot keep pace with platelet destruction. Evidence for increased platelet destruction is thrombocytopenia following ITP plasma infusions in normal subjects, in vitro platelet phagocytosis, and decreased platelet survivals in ITP patients that respond to therapies that prevent in vivo platelet phagocytosis; e.g., intravenous immunoglobulin G, anti-D, corticosteroids, and splenectomy. The cause of platelet destruction in most ITP patients appears to be autoantibody-mediated. However, cytotoxic T lymphocyte-mediated platelet (and possibly megakaryocyte) lysis, may also be important. Studies supporting suppressed platelet production include: reduced platelet turnover in over 80% of ITP patients, morphological evidence of megakaryocyte damage, autoantibody-induced suppression of in vitro megakaryocytopoiesis, and increased platelet counts in most ITP patients following treatment with thrombopoietin receptor agonists. This review summarizes data that indicates that the pathogenesis of chronic ITP may be due to both immune-mediated platelet destruction and/or suppressed platelet production. The relative importance of these two mechanisms undoubtedly varies among patients.
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Off-label use of rFVIIa in children with excessive bleeding: a consecutive study of 153 off-label uses in 139 children.
Pediatr Blood Cancer
PUBLISHED: 05-06-2009
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Recombinant factor VIIa is a general hemostatic agent. Randomized trials have demonstrated effectiveness in adults; however, data in children are confined to case reports and series subject to publication bias.
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Lack of association between aspirin responsiveness and seven candidate gene haplotypes in patients with symptomatic vascular disease.
Thromb. Haemost.
PUBLISHED: 01-10-2009
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We studied the effect of prophylactic aspirin (ASA) ingestion on platelet function in 463 patients with stroke, transient ischemic attack (TIA) or acute coronary disease (ACD), using the Platelet Function Analyzer-100 (PFA-100). We correlated ASA responsiveness with haplotypes of seven candidate genes, selected for their documented role in platelet function, namely, the genes for integrins alpha2beta1and alphaIIbbeta3 (ITGA2, ITGA2B, and ITGB3), platelet glycoproteins Ibalpha and VI (GPIBA and GP6), the purinergic receptor P2Y1 (P2RY1), and prostaglandin H synthase 1 (PTGS1 = COX1). Non-responsiveness to ASA was defined as the failure of prior ASA ingestion to prolong the PFA-100 closure time (CT) when blood was perfused through cartridges coated with collagen plus epinephrine (CEPI-CT). ASA non-responsiveness was observed in 114 of 463 patients (24.6 %), but was not associated with haplotypes of any of the seven candidate genes. There was also no association between any haplotypes and the CT when blood was perfused through cartridges coated with collagen plus ADP (CADP-CT). The ASA non-responsive cohort had significantly increased whole blood platelet counts (p = 0.03) and plasma von Willebrand Factor antigen levels (p < 0.001), which likely contributes to resistance to the inhibitory effects of ASA in the PFA-100.
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Corifact™/Fibrogammin® P in the prophylactic treatment of hereditary factor XIII deficiency: results of a prospective, multicenter, open-label study.
Thromb. Res.
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Factor XIII (FXIII) deficiency is an extremely rare congenital condition that is associated with a high risk of potentially life-threatening intracranial hemorrhage, poor wound healing, spontaneous abortion, and a life-long tendency towards spontaneous bleeding and severe bleeding after trauma or surgery. Routine prophylaxis with FXIII concentrate is recommended in all individuals with FXIII levels <1 IU/dL from the time of diagnosis, and in some severely affected patients with FXIII levels of 1-4 IU/dL. Fibrogammin® P is a highly purified, pasteurized, plasma-derived concentrate that has been available in Europe and other countries since 1993 and has recently been approved as Corifact™ in the USA. To support the US registration of Corifact™, a 52-week, prospective, multicenter, open-label study was conducted in 41 patients (mean age 19 years; range <1-42 years) with congenital FXIII deficiency. Corifact™/Fibrogammin® P was administered intravenously at an initial dose of 40 IU/kg every 4 weeks, with dosing adjusted to maintain a trough FXIII activity level of 5-20%. No spontaneous bleeding episodes requiring FXIII treatment were reported during the study (primary endpoint). Preoperative use of Corifact™/Fibrogammin® P successfully prevented postoperative bleeding in two surgeries. Corifact™/Fibrogammin® P was well tolerated during a total exposure of ? 455 subject-months. No patient withdrew from treatment, and there were no reports of virus transmission or thromboembolism-related events. This study adds to the wealth of data gained from clinical trials and almost 20 years of clinical use confirming that Corifact™/Fibrogammin® P is an effective and well-tolerated prophylactic treatment for congenital FXIII deficiency.
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Successful cord blood transplantation in a patient with malignant infantile osteopetrosis and hemophilia.
Pediatr Transplant
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MIOP is a congenital disorder of osteoclast differentiation or dysfunction. Inadequate bone resorption by osteoclasts results in a spectrum of complications including hypocalcemia, osteosclerosis, marrow failure, extramedullary hematopoiesis, hydrocephalus, visual deficits, and eventual mortality. Early diagnosis and timely HCT is a recommended treatment approach for select patients prior to the development of end-organ damage. A comorbid bleeding disorder presents a unique challenge in the setting of MIOP and cord blood HCT given the additional risk factors for bleeding including delayed engraftment, a high risk of developing sinusoidal obstruction syndrome, and potential need for emergent invasive procedures. To our knowledge, this is the first report of a patient with an autosomal recessive form of MIOP who successfully underwent a cord blood HCT complicated by the presence of mild hemophilia A and HCT-related complications including delayed engraftment, sinusoidal obstruction syndrome, and need for multiple invasive procedures (e.g., ventriculostomy, tracheostomy) without clinically significant bleeding. Given the underlying diagnosis of MIOP and need for HCT, the challenge of mitigating the significant risk of bleeding in a patient with a comorbid bleeding disorder is discussed.
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Rare factor deficiencies.
Curr. Opin. Hematol.
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By definition, rare factor deficiencies have a prevalence of less than 200,000 in the US population, or an incidence of less than one in 2000 in Europe. The very small numbers of patients with rare disorders present challenges in diagnosis, evaluation of bleeding risk and treatment. Use of new assays, full genome sequencing, and global clotting assays will significantly improve diagnosis of patients with rare bleeding disorders.
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Genetic variants that affect platelet function.
Curr. Opin. Hematol.
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This review summarizes our current knowledge of common gene variants (polymorphisms) that have small individual effects on platelet function in humans, but can cumulatively lead to hyperreactive platelets and increase risk for negative outcomes in thrombotic disorders.
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Late effects in hematopoietic cell transplant recipients with acquired severe aplastic anemia: a report from the late effects working committee of the center for international blood and marrow transplant research.
Biol. Blood Marrow Transplant.
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With improvements in hematopoietic cell transplant (HCT) outcomes for severe aplastic anemia (SAA), there is a growing population of SAA survivors after HCT. However, there is a paucity of information regarding late effects that occur after HCT in SAA survivors. This study describes the malignant and nonmalignant late effects in survivors with SAA after HCT. A descriptive analysis was conducted of 1718 patients post-HCT for acquired SAA between 1995 and 2006 reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). The prevalence and cumulative incidence estimates of late effects are reported for 1-year HCT survivors with SAA. Of the HCT recipients, 1176 (68.5%) and 542 (31.5%) patients underwent a matched sibling donor (MSD) or unrelated donor (URD) HCT, respectively. The median age at the time of HCT was 20 years. The median interval from diagnosis to transplantation was 3 months for MSD HCT and 14 months for URD HCT. The median follow-up was 70 months and 67 months for MSD and URD HCT survivors, respectively. Overall survival at 1 year, 2 years, and 5 years for the entire cohort was 76% (95% confidence interval [CI]: 74-78), 73% (95% CI: 71-75), and 70% (95% CI: 68-72). Among 1-year survivors of MSD HCT, 6% had 1 late effect and 1% had multiple late effects. For 1-year survivors of URD HCT, 13% had 1 late effect and 2% had multiple late effects. Among survivors of MSD HCT, the cumulative incidence estimates of developing late effects were all <3% and did not increase over time. In contrast, for recipients of URD HCT, the cumulative incidence of developing several late effects exceeded 3% by 5 years: gonadal dysfunction 10.5% (95% CI: 7.3-14.3), growth disturbance 7.2% (95% CI: 4.4-10.7), avascular necrosis 6.3% (95% CI: 3.6-9.7), hypothyroidism 5.5% (95% CI: 2.8-9.0), and cataracts 5.1% (95% CI: 2.9-8.0). Our results indicated that all patients undergoing HCT for SAA remain at risk for late effects, must be counseled about, and should be monitored for late effects for the remainder of their lives.
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Recombinant factor XIII: a safe and novel treatment for congenital factor XIII deficiency.
Blood
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Congenital factor XIII (FXIII) deficiency is a rare, autosomal-recessive disorder, with most patients having an A-subunit (FXIII-A) deficiency. Patients experience life-threatening bleeds, impaired wound healing, and spontaneous abortions. In many countries, only plasma or cryoprecipitate treatments are available, but these carry a risk for allergic reactions and infection with blood-borne pathogens. The present study was a multinational, open-label, single-arm, phase 3 prophylaxis trial evaluating the efficacy and safety of a novel recombinant FXIII (rFXIII) in congenital FXIII-A subunit deficiency. Forty-one patients ? 6 years of age (mean, 26.4; range, 7-60) with congenital FXIII-A subunit deficiency were enrolled. Throughout the rFXIII prophylaxis, only 5 bleeding episodes (all trauma induced) in 4 patients were treated with FXIII-containing products. The crude mean bleeding rate was significantly lower than the historic bleeding rate (0.138 vs 2.91 bleeds/patient/year, respectively) for on-demand treatment. Transient, non-neutralizing, low-titer anti-rFXIII Abs developed in 4 patients, none of whom experienced allergic reactions, any bleeds requiring treatment, or changes in FXIII pharmacokinetics during the trial or follow-up. These non-neutralizing Abs declined below detection limits in all 4 patients despite further exposure to rFXIII or other FXIII-containing products. We conclude that rFXIII is safe and effective in preventing bleeding episodes in patients with congenital FXIII-A subunit deficiency. This study is registered at http://www..clinicaltrials.gov as number NCT00713648.
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X-linked hyper IgM syndrome: a novel sequence variant associated with an atypical mild phenotype.
J. Pediatr. Hematol. Oncol.
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X-linked hyper IgM syndrome is associated with abnormalities in the gene encoding CD40 ligand (CD40LG). A typical phenotype evolves during infancy in affected males. This phenotype includes neutropenia, dysgammaglobulinemia, bacterial sinopulmonary infections, and opportunistic infections. In the absence of the typical phenotypic features, clinicians must maintain a high level of suspicion for X-linked hyper IgM syndrome. We describe a unique hemizygous CD40LG mutation which was discovered in a 12-year-old boy with chronic severe neutropenia, a normal IgG level, and absence of sinopulmonary or opportunistic infections. The clinical implications of this mutation and associated atypical phenotype are discussed.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.