Higher rates of bleeding and use of treatment products among young boys compared to girls with von Willebrand disease.

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 <.001)] compared to girls. Understanding phenotypic bleeding characteristics, well-being status, treatment, and higher risk groups for bleeding among pre-adolescent children with VWD will aid physicians in efforts to educate families about bleeding symptoms.

Characteristics, complications, and sites of bleeding among infants and toddlers less than 2 years of age with VWD.

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 <2 years of age. In 68% of the patients, the reason for diagnostic testing was a family history of a bleeding disorder. The mean age at diagnosis was 7 months, with little variation by sex. Patients with type 2 VWD were diagnosed earlier than those with types 1 or 3 (P = .04), and those with a family history were diagnosed ∼4 months earlier than those with none (P < .001). Among the patients who experienced a bleeding event (70%), oral mucosa was the most common site of the initial bleeding episode (32%), followed by circumcision-related (12%) and intracranial/extracranial bleeding (10%). Forty-one percent of the initial bleeding events occurred before 6 months of age, and 68% of them occurred before the age of 1 year. Approximately 5% of the cohort experienced an intracranial hemorrhage; however, none was associated with delivery at birth. Bleeding patterns and rates were similar by sex (P = .40) and VWD type (P = .10). Forty-seven percent were treated with plasma-derived von Willebrand factor VIII concentrates. The results of this study indicate that a high percentage of ITs diagnosed with VWD and receiving care within the multidisciplinary structure of the USHTCN have a family history of VWD. In addition, bleeding events such as circumcision-related, oropharyngeal, and intracranial or extracranial episodes are common and are leading indicators for treatment.

Evaluation of CDC's Hemophilia Surveillance Program - Universal Data Collection (1998-2011) and Community Counts (2011-2019), United States.

PROBLEM/CONDITION: Hemophilia is an X-linked genetic disorder that primarily affects males and results in deficiencies in blood-clotting proteins. Hemophilia A is a deficiency in factor VIII, and hemophilia B is a deficiency in factor IX. Approximately one in 5,000 males are born with hemophilia, and hemophilia A is about four times as common as hemophilia B. Both disorders are characterized by spontaneous internal bleeding and excessive bleeding after injuries or surgery. Hemophilia can lead to repeated bleeding into the joints and associated chronic joint disease, neurologic damage, damage to other organ systems, and death. Although no precise national U.S. prevalence estimates for hemophilia exist because of the difficulty identifying cases among persons who receive care from various types of health care providers, two previous state-based studies estimated hemophilia prevalence at 13.4 and 19.4 per 100,000 males. In addition, these studies showed that 67% and 82% of persons with hemophilia received care in a federally funded hemophilia treatment center (HTC), and 86% and 94% of those with the most severe cases of hemophilia (i.e., those with the lowest levels of clotting factor activity in the circulating blood) received care in a federally funded HTC. As of January 2020, the United States had 144 HTCs. PERIOD COVERED: 1998-2019. DESCRIPTION OF THE SYSTEM: Surveillance for hemophilia, which is a complex, chronic condition, is challenging because of its low prevalence, the difficulty in ascertaining cases uniformly, and the challenges in routinely characterizing and tracking associated health complications. Over time, two systems involving many stakeholders have been used to conduct ongoing hemophilia surveillance. During 1998-2011, CDC and the HTCs collaborated to establish the Universal Data Collection (UDC) surveillance system. The purposes of the UDC surveillance system were to monitor human immunodeficiency virus (HIV) and bloodborne viral hepatitis in persons with hemophilia, thereby tracking blood safety, and to track the prevalence of and trends in complications associated with hemophilia. HTC staff collected clinical data and blood specimens from UDC participants and submitted them to CDC. CDC tested specimens for viral hepatitis and HIV. In 2011, the UDC surveillance system was replaced by a new hemophilia surveillance system called Community Counts. CDC and the HTCs established Community Counts to expand laboratory testing and the collection of clinical data to better identify and track emerging health issues in persons with hemophilia. RESULTS: This report is the first comprehensive summary of CDC's hemophilia surveillance program, which comprises both UDC and Community Counts. Data generated from these surveillance systems have been used in the development of public health and clinical guidelines and practices to improve the safety of U.S. blood products and either prevent hemophilia-related complications or identify complications early. Several factors have played a role in the effectiveness of the UDC and Community Counts systems, including 1) a stable data collection design that was developed and is continually reviewed in close partnership with HTC regional leaders and providers to ensure surveillance activities are focused on maximizing the scientific and clinical impact; 2) flexibility to respond to emerging health priorities through periodic updates to data collection elements and special studies; 3) high data quality for many clinical indicators and state-of-the-art laboratory testing methods for hemophilia treatment product inhibitors (developed and refined in part based on CDC research); 4) timely data and specimen collection and submission, laboratory specimen testing, analysis, and reporting; and 5) the largest and most representative sample of persons with hemophilia in the United States and one of the largest and most comprehensive data collection systems on hemophilia worldwide. INTERPRETATION: CDC has successfully developed, implemented, and maintained a surveillance system for hemophilia. The program can serve as an example of how to conduct surveillance for a complex chronic disease by involving stakeholders, improving and building new infrastructure, expanding data collection (e.g., new diagnostic assays), providing testing guidance, establishing a registry with specimen collection, and integrating laboratory findings in clinical practice for the individual patient. PUBLIC HEALTH ACTION: Hemophilia is associated with substantial lifelong morbidity, excess premature deaths, and extensive health care needs throughout life. Through monitoring data from Community Counts, CDC will continue to characterize the benefits and adverse events associated with existing or new hemophilia treatment products, thereby contributing to maximizing the health and longevity of persons with hemophilia.

A public health approach to the prevention of inhibitors in hemophilia.

The development of an antibody in people with hemophilia to products used in the treatment and prevention of bleeding, also referred to as an inhibitor, is the most serious complication of hemophilia care today. CDC, together with healthcare providers, consumer organizations, hemophilia organizations, and federal partners, has developed a public health agenda to prevent the development of inhibitors. This paper describes a public health approach that combines a national surveillance program with epidemiologic, laboratory, and prevention research to address knowledge gaps in rates and risk factors for inhibitor development, and in knowledge and behaviors of patients and providers, in addition to screening and treatment practices.

Public health surveillance of nonmalignant blood disorders.

Nonmalignant blood disorders currently affect millions of Americans, and their prevalence is expected to grow over the next several decades. This is owing to improvements in treatment leading to increased life expectancy of people with hereditary conditions, like sickle cell disease and hemophilia, but also the rising occurrence of risk factors for venous thromboembolism. The lack of adequate surveillance systems to monitor these conditions and their associated health indicators is a significant barrier to successfully assess, inform, and measure prevention efforts and progress toward national health goals. CDC is strengthening surveillance activities for blood disorders by improving and developing new methods that are tailored to best capture and monitor the epidemiologic characteristics unique to each disorder. These activities will provide a robust evidence base for public health action to improve the health of patients affected by or at risk for these disorders.

The universal data collection surveillance system for rare bleeding disorders.

Since 1998, the CDC has coordinated a national public health surveillance project-the Universal Data Collection (UDC) program-on chronic, rare, inherited bleeding disorders. In this program, uniform data are gathered through a network of 130 hemophilia treatment centers (HTCs) throughout the U.S. and its territories. Initially, the program was designed to address two primary goals: (1) establishment of a blood-safety monitoring system among people with bleeding disorders, and (2) collection of a uniform set of clinical outcomes data that could be used to monitor trends in the prevalence of infectious diseases and joint complications among this population. To this end, the program has been acquiring useful longitudinal data to monitor complications of bleeding disorders. For example, with the establishment of range-of-motion measurements for joints as required data elements, a large database has been developed for studies examining risk factors for joint-disease progression. The UDC program data have been used to provide evidence for a national prevention campaign to promote the need for patients with hemophilia to establish or maintain a healthy weight to help prevent joint disease. Risk factors leading to complications such as joint infection have also been identified. The application of geographic information systems technology to UDC program data has helped identify needs for outreach and availability of blood products and sources of care. Future analyses of data collected on babies, women, and individuals with rarer bleeding disorders than hemophilia will provide further information, leading to improved public health prevention strategies.

Parvovirus B19 transmission by a high-purity factor VIII concentrate.

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 x 10(3) 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 2x10(4) IU (or geq) of B19 DNA, which was present in this S/D-treated, high-purity AHF product.