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Data on infants and toddlers (ITs) with von Willebrand disease (VWD) are lacking. We used data collected in the US Hemophilia Treatment Center Network (USHTCN) to describe birth characteristics, bleeding episodes, and complications experienced by 105 patients with VWD who were

There are limited observational studies among children diagnosed with von Willebrand Disease (VWD). We analyzed differences in bleeding characteristics by sex and type of VWD using the largest reported surveillance database of children with VWD (n = 2712), ages 2 to 12 years old. We found that the mean ages of first bleed and diagnosis were lowest among children with type 3 VWD. It was even lower among boys than girls among all VWD types, with statistically significant difference among children with type 1 or type 3 VWD. Children with type 3 VWD also reported higher proportions of ever having a bleed compared to other VWD types, with statistically higher proportions of boys compared to girls reporting ever having a bleed with type 1 and type 2 VWD. A similar pattern was observed with the use of treatment product, showing higher usage among type 3 VWD, and among boys than girls with type 1 and type 2 VWD. While there were no differences in life quality or in well-being status by sex, children with type 3 VWD showed a greater need for mobility assistance compared to children with type 1 and type 2 VWD. In an adjusted analysis among children with type 1 VWD, boys showed a significant association of ever bleeding [hazard ratio 1.4; P-value

BACKGROUND: Parvovirus B19 (B19) is known to cause a variety of human diseases in susceptible individuals by close contact via the respiratory route or by transfusion of contaminated blood or blood products. In this study, whether a case of B19 transmission was causally related to the infusion of implicated lots of a solvent/detergent (S/D)-treated, immunoaffinity-purified factor VIII concentrate (antihemophilic factor [human][AHF]) was investigated. STUDY DESIGN AND METHODS: Anti-B19 (both immunoglobulin M [IgM] and immunoglobulin G [IgG]) and B19 DNA (by a nucleic acid testing [NAT] procedure) were assayed in two implicated product lots, a plasma pool, and a recipient's serum sample. Analysis of the partial B19 sequences obtained from sequencing clones or direct sequencing of the samples was performed. RESULTS: Only one of the two implicated lots was B19 DNA–positive. It contained 1.3 × 103 genome equivalents (geq or international units [IU]) per mL. The negative lot was derived from plasma screened for B19 DNA by NAT in a minipool format to exclude high-titer donations, whereas the positive lot was mostly from unscreened plasma. This high-purity AHF product had no detectable anti-B19 IgG. A 4-week postinfusion serum sample from a recipient, who received both lots and became ill, was positive for the presence of B19 antibodies (both IgM and IgG) as well as B19 DNA. The B19 sequences from the positive lot, its plasma pool, and the recipient's serum sample were closely related. CONCLUSION: These findings and the recipient's clinical history support a causal relationship between the implicated AHF product and B19 infection in this recipient. The seronegative patient became infected after receiving 2 × 104 IU (or geq) of B19 DNA, which was present in this S/D-treated, high-purity AHF product.

Background: Continuous prophylaxis, or the routine replacement of deficient clotting factor, is the standard of care therapy for individuals with severe hemophilia A and joint bleeding. In the United States (US), the majority of eligible patients are prescribed continuous prophylaxis, including approximately 75% of children < 20 years of age. However, up to 30% of severe hemophilia A patients develop neutralizing alloantibodies that render factor replacement ineffective requiring inhibitor eradication through induction of immune tolerance (ITI) therapy. Tolerized patients demonstrate successful elimination of inhibitors and normal response to FVIII concentrates. Non-tolerized patients can also be treated on prophylaxis using bypassing agents. Aim: This analysis used national surveillance data to compare joint and other outcomes in persons with severe hemophilia A on continuous prophylaxis in three groups: no history of an inhibitor, likely tolerized inhibitor and active (non-tolerized) inhibitor. Methods: The Community Counts bleeding disorders surveillance project is funded by the Centers for Disease Control and Prevention (CDC) through a cooperative agreement awarded to the American Thrombosis and Hemostasis Network (ATHN) in partnership with the US Hemophilia Treatment Center Network (USHTCN). The Registry for Bleeding Disorders Surveillance component collects detailed medical information on patients with bleeding disorders who receive treatment within the USHTCN. Likely tolerized inhibitors were defined as having a history of a previous inhibitor and currently being treated with FVIII concentrate; active inhibitors were defined as having a history of a previous inhibitor and being treated with bypassing agents. Using the Registry component, the following data elements, stratified by age and inhibitor status, were extracted from the initial visit form: demographics, treatment regimen, mobility, cumulative joint bleeding, invasive joint procedures, pain and opioid use. Results: Data on 1,300 persons with severe hemophilia A were analyzed including: 739 with a negative inhibitor history; 410 likely tolerized inhibitor patients; and 151 with an active inhibitor. The 410 patients represented 73% of participants with a positive inhibitor history, similar to the North American Inhibitor Registry (DiMichele D, Haemophilia 2009;15:320-8). Participants with likely tolerized inhibitors were treated using continuous prophylaxis in similar proportion to participants with no history of inhibitor (83% vs 78%, respectively), and more often than participants with active inhibitor (83% vs 65%); however outcomes of participants on continuous prophylaxis were similar in all three groups (Table 1). Patients < 20 years of age had less disability, and fewer joint bleeds, invasive procedures, pain and opioid use compared with adult participants. Conclusions: Improved outcomes on preventive strategies may be best determined prospectively in younger patients due to the lesser degree of established morbidity. Persons with severe hemophilia A on continuous prophylaxis with likely tolerized inhibitors (using FVIII) or with active inhibitors (using bypassing agents) demonstrate outcomes similar to those without inhibitors. However, more age- and treatment regimen- stratified analysis is needed for more precise comparisons. Future findings may contribute to the perspective that prophylaxis should be the standard of care for all hemophilia patients regardless of inhibitor status. Disclosures Manco-Johnson: Bayer: Honoraria, Research Funding; Baxalta: Honoraria; NovoNordisk: Honoraria; BiogenIdec: Honoraria; CSL Behring: Honoraria. Kulkarni:Baxter: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novo Nordisk: Membership on an entity's Board of Directors or advisory committees, Research Funding; BPL: Membership on an entity's Board of Directors or advisory committees; Kedrion: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Biogen: Research Funding, Speakers Bureau. Buckner:Novo Nordisk: Consultancy; Genentech: Consultancy; Baxalta: Consultancy.

To determine mortality rates and risk factors among males with hemophilia who receive care in federally supported HTCs, we analyzed mortality data on the 85% of HTC patients voluntarily enrolled in UDC. Demographic, diagnostic, clinical, and treatment data were collected for all UDC patients on a standard form at annual comprehensive care visits. Proportion of expected annual UDC visits for each patient was the number of visits attended divided by the number of years between UDC enrollment and the end of the study. Blood specimens were tested centrally for markers of hepatitis and HIV infection. Data on mortality including date and causes of death was submitted by HTC staff using a standard form. Follow-up began at initial UDC visit and continued until date of death or December 31, 2006, whichever came first. Mortality rates were calculated as the number of deaths divided by person time and multiplied by 10,000 (deaths /104 person years PY). Univariate associations used the relative risk and multivariate analysis used Cox proportional hazards regression. Over the study period, 12,883 males with hemophilia ≥2 years old were enrolled in UDC and followed for a total of 68,060 PY. Among UDC participants there were 451 deaths for an overall mortality rate of 66.3 /104 PY. Hemophilia (14.2%), HIV (17.5%), and liver (29.1%) related causes of death were most commonly specified. As expected, mortality was strongly associated with age and ranged from 2.5 /104 PY for 2–10 year olds to 270 /104 PY for those >60 years. Also significantly associated with higher mortality in univariate analyses were Native American (NA) race vs. white, hemophilia A vs. B, severe vs. non-severe disease, HIV infection, hepatitis B active and past infection, hepatitis C infection, any restriction in activity level vs. none, increasing body mass index (BMI), history of intracranial hemorrhage (ICH), alcohol abuse, and any sign of liver disease including jaundice, ascites, varices, or elevated ALT/AST or PT. On the other hand, patients who attended from 1/3 to 2/3 of their expected UDC visits were 60% less likely to die and those who attended more than 2/3 of expected UDC visits were 90% less likely to die than those patients who attended less than 1/3 of their expected UDC visits. The distribution of patients attending 2/3 of expected visits was 15.3%, 31.3% and 53.4%, respectively. A multivariate model including all risk factors indicated that NA race RR=2.6 (95% CI: 1.2, 5.6), HIV infection RR=3.3 (2.6, 4.3), severe disease RR=1.8 (1.4, 2.3), alcohol abuse RR=1.3 (1.0, 1.7), jaundice RR=2.0 (1.4, 3.0), ascites RR=1.5 (1.0, 2.4), varices RR=2.0 (1.3, 3.1), elevated ALT/AST RR=1.4 (1.1, 1.8), and elevated PT RR=1.5 (1.1, 2.1) increased risk for mortality. Whereas attending 1/3 to 2/3 expected visits RR=0.36 (0.29, 0.44), attending >2/3 expected visits RR=0.07 (0.05, 0.10) and 10 unit increase in BMI RR=0.72 (0.58, 0.90) were protective against mortality. Hemophilia type, activity restriction, history of ICH, and hepatitis B and C infection were no longer significantly associated with death in the multivariate model. Our finding that patients enrolled in the UDC project who returned regularly to HTCs for comprehensive care were much less likely to die, even after adjusting for other mortality risk factors, supports results of previous studies that showed lower mortality among patients receiving comprehensive care in HTCs.