Executive summary of the NHLBI State of the Science (SOS) Workshop: Overview and next steps in generating a national blueprint for future research on factor VIII inhibitors

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/150611/1/hae13713_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150611/2/hae13713.pd

Septic arthritis in males with haemophilia

We used data collected as part of the Universal Data Collection (UDC) surveillance project in haemophilia treatment centers (HTC) to study the incidence, risk factors, and impact of septic arthritis among males with haemophilia. Patients participating in UDC on 2 or more occasions were included. Cases were defined as patients with documented joint infection. Characteristics of the cases were compared with those of haemophilia patients without infection. Among the 8026 eligible patients with 36,015 person-years of follow-up, 30 (0.37%) had a documented joint infection (incidence rate 83 per 100,000 person-years). In a logistic regression model, only increasing age (OR = 6.1 for age ≥30), race/ethnicity other than white (OR = 3.9), presence of inhibitor (OR = 3.9), invasive procedure in the past year (OR = 2.7) and presence of one or more target joints (OR = 3.2) remained statistically significant. CVAD use and HCV and HIV infection were not associated with septic arthritis risk after adjusting for potential confounders. Study limitations include possible underestimation of septic arthritis rate in this population and its retrospective design. We conclude that septic arthritis is an uncommon complication of haemophilia occurring primarily in joints most affected by bleeding and reparative surgical interventions

National surveillance for hemophilia inhibitors in the United States: Summary report of an expert meeting: National Inhibitor Surveillance in the U.S.

On March 12, 2012, the Centers for Disease Control and Prevention (CDC) held a meeting of its partners in hemophilia treatment, community-based organizations, industry, and government to review data and discuss implementation issues relevant to planned United States (U.S.) national inhibitor surveillance. Issues discussed included the current status of inhibitor surveillance in the United Kingdom (UK) and the US, the results of a US inhibitor surveillance feasibility study, proposed national surveillance schemes, laboratory testing and reporting issues and potential opportunities for future inhibitor-related research. It was concluded that implementation of a national program of inhibitor surveillance using standardized testing through an established public health registry along with patient and care provider education and targeted research provide the best opportunity to inform efforts to develop and evaluate effective prevention strategies

Evidence for the transmission of parvovirus B19 in patients with bleeding disorders treated with plasma-derived factor concentrates in the era of nucleic acid test screening: TRANSMISSION OF B19V

Parvovirus B19 (B19V) is a small, non-enveloped virus that typically causes a benign flu-like illness that occurs most frequently in childhood. The virus is resistant to current viral inactivation steps used in the manufacture of anti-hemophilic factor concentrates and B19V transmission through these products has been documented. Since 2000, B19V nucleic acid test (NAT) screening of plasma pools has been implemented to further decrease the viral burden in these products, but no study has examined populations using these products to assess the impact of the screening on B19V transmission

Loss of Function of TET2 Cooperates with Constitutively Active KIT in Murine and Human Models of Mastocytosis

Systemic Mastocytosis (SM) is a clonal disease characterized by abnormal accumulation of mast cells in multiple organs. Clinical presentations of the disease vary widely from indolent to aggressive forms, and to the exceedingly rare mast cell leukemia. Current treatment of aggressive SM and mast cell leukemia is unsatisfactory. An imatinib-resistant activating mutation of the receptor tyrosine kinase KIT (KIT D816V) is most frequently present in transformed mast cells and is associated with all clinical forms of the disease. Thus the etiology of the variable clinical aggressiveness of abnormal mast cells in SM is unclear. TET2 appears to be mutated in primary human samples in aggressive types of SM, suggesting a possible role in disease modification. In this report, we demonstrate the cooperation between KIT D816V and loss of function of TET2 in mast cell transformation and demonstrate a more aggressive phenotype in a murine model of SM when both mutations are present in progenitor cells. We exploit these findings to validate a combination treatment strategy targeting the epigenetic deregulation caused by loss of TET2 and the constitutively active KIT receptor for the treatment of patients with aggressive SM

Burden of disease resulting from hemophilia in the U.S.

BACKGROUND: Hemophilia is a hereditary bleeding disorder. Its complications can result in substantial morbidity, but few efforts have been made to quantify the disease burden. PURPOSE: The objective of this analysis was to estimate the burden of disease due to hemophilia (A and B) in the U.S., using disability-adjusted life years (DALY). METHODS: The approach taken by the WHO in its Global Burden of Disease study was followed. Assumptions were drawn from published literature, and population estimates from the U.S. Census Bureau for the Year 2007 were used. Estimations of years of life lost resulting from mortality (YLL) and years of life lost resulting from morbidity (YLD) were done separately by gender, 5-year age intervals, and severity of disease (morbidity only) with their sum representing DALYs. Disability weights were derived from the quality-of-life tool EuroQol (EQ-5D). The stability of burden estimates was tested by performing sensitivity analyses, changing one assumption at a time. RESULTS: In the U.S. in 2007, hemophilia resulted in 110,095 DALYs, composed of 13,418 YLLs and 96,677 YLDs. Large differences between men/boys (107,346) and women/girls (2749) were observed, given that females are genetic carriers of the disorder and rarely present with disease. Sensitivity analyses revealed a relatively robust estimate with a maximum variation of 4.49%. CONCLUSIONS: This first estimate of hemophilia-related DALYs in the U.S. indicates that control of hemophilia can potentially result in a gain of 1 healthy year of life for every 2700 people in the population