Last data update: Sep 23, 2024. (Total: 47723 publications since 2009)
Records 1-30 (of 67 Records) |
Query Trace: Soucie M [original query] |
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Prevalence of comorbid conditions among older males with haemophilia receiving care in haemophilia treatment centers in the United States
Soucie JM , Le B , Dupervil B , Poston JN . Haemophilia 2022 28 (6) 986-995 INTRODUCTION: Increased survival among men with haemophilia has brought with it an increased risk of age-related comorbidities that may be challenging to treat in the presence of a bleeding disorder. AIM: Estimate the prevalence of several age-related comorbidities among older males with haemophilia receiving care in the U.S. haemophilia treatment center (HTC) network compared to that among the general population. METHODS: People with bleeding disorders who receive care in network HTCs can volunteer to participate in a surveillance registry that collects detailed clinical information including the presence of comorbid conditions at annual visits. We used registry data collected on males with haemophilia age 45 years and older to calculate lifetime prevalence of obesity, diabetes, hypertension, cardiovascular disease, renal disease, cancer, anxiety and depression. Comparable data on the U.S. general male population was obtained from the National Health Interview Survey. RESULTS: During the surveillance period, 1592 middle-aged (45-64 years) and 645 older (≥65 years) patients with haemophilia had comorbidity data collected during 6435 HTC visits. Most haemophilia patients in both age groups had a higher prevalence of anxiety, depression and diabetes, but a lower prevalence of hypertension, coronary heart disease, stroke and myocardial infarction compared to the general U.S. male population. In addition, middle-aged patients had lower rates of leukemia, whereas older patients had higher rates of obesity than the general population. CONCLUSION: These findings highlight the mental stress associated with this chronic condition and support continued public health obesity prevention efforts in the haemophilia community. |
Occurrence rates of inherited bleeding disorders other than haemophilia and von Willebrand disease among people receiving care in specialized treatment centres in the United States
Miller CH , Soucie JM , Byams VR , Payne AB , Abe K , Lewandowska M , Shapiro AD . Haemophilia 2022 28 (3) e75-e78 The United States Hemophilia Treatment Centers Network (USHTCN) is made up of 145 haemophilia treatment centres (HTCs) located throughout the United States with funding from the Health Resources and Service Administration and the Centers for Disease Control and Prevention (CDC) to facilitate monitoring of health care and outcomes among people with bleeding disorders. Inherited bleeding disorders most often treated at US HTCs are hemophilia1, 2 and von Willebrand disease (VWD)3; however, these centres also provide care for people with a variety of other disorders, including deficiencies of coagulation factors other than factor VIII and IX, platelet disorders, fibrinolytic defects, and connective tissue disorders with an associated bleeding phenotype. Community Counts,4 a combined effort of the USHTCN, the American Thrombosis and Hemostasis Network (ATHN), and the CDC to gather and share information about common health issues, medical complications, and causes of death of people with bleeding disorders, includes a component known as the HTC Population Profile (HTC PP), for which limited data on all persons receiving care at HTCs have been collected since 2012. We have recently reported numbers and characteristics of males and females with hemophilia1, 2 and VWD3 treated at HTCs using HTC PP data. The aim of this study was to use data from the HTC PP to estimate the number of people with rare bleeding disorders other than haemophilia and VWD receiving care at HTCs in the United States. |
Women and girls with haemophilia receiving care at specialized haemophilia treatment centres in the United States
Miller CH , Soucie JM , Byams VR , Payne AB , Sidonio RF Jr , Buckner TW , Bean CJ . Haemophilia 2021 27 (6) 1037-1044 INTRODUCTION: Females may have haemophilia with the same factor VIII (FVIII) or factor IX (FIX) levels as affected males. Characterization of females with haemophilia would be useful for health care planning to meet their unique needs. Federally-funded haemophilia treatment centres (HTCs) in the United States contribute data on all individuals with bleeding disorders receiving care to the Population Profile (HTC PP) component of the Community Counts Public Health Surveillance of Bleeding Disorders project. AIMS: To estimate the number of females with haemophilia receiving care at HTCs in the United States and compare their characteristics with those of males with haemophilia. METHODS: HTC PP data collected on people receiving care at an HTC from January 2012 through September 2020 with haemophilia A and B were evaluated by sex for demographic and clinical characteristics. RESULTS: A factor level < 40% was reported for 23,196 males (97.8%) and 1667 females (47.6%) attending HTCs; 51 (.48%) severe, 79 (1.4%) moderate, and 1537 (17.9%) mild haemophilia patients were female. Females were older, more often White, and less often non-Hispanic than males. Females were less likely to have history of HIV or HCV infection, even among those with severe disease, but twice as likely to have infection status unknown. Females with mild haemophilia were more often uninsured than males. CONCLUSIONS: Females with severe or moderate haemophilia are uncommon, even in specialized care centres; however, almost one in five patients with mild haemophilia was female, indicating needs for specialized care based on factor level and history for affected females. |
Characteristics, complications, and sites of bleeding among infants and toddlers less than 2 years of age with VWD.
Dupervil B , Abe K , O'Brien SH , Oakley M , Kulkarni R , Thornburg CD , Byams VR , Soucie JM . Blood Adv 2021 5 (8) 2079-2086 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. |
Occurrence rates of von Willebrand disease among people receiving care in specialized treatment centres in the United States.
Michael Soucie J , Miller CH , Byams VR , Payne AB , Abe K , Sidonio RF Jr , Kouides PA . Haemophilia 2021 27 (3) 445-453 INTRODUCTION: In the network of U.S. comprehensive haemophilia treatment centres (HTCs), von Willebrand disease (VWD) is the most common bleeding disorder other than haemophilia. Estimates of the size and characteristics of the VWD population receiving treatment are useful for healthcare planning. AIM: Estimate the prevalence and incidence of VWD among males and females receiving care at U.S. HTCs (HTC-treated prevalence and incidence). METHODS: During the period 2012-2019, de-identified surveillance data were collected on all VWD patients who visited an HTC including year of birth, sex, race, Hispanic ethnicity, VWD type, and laboratory findings and used to calculate period HTC-treated prevalence by VWD type and sex. Data from patients born 1995-1999 were used to estimate HTC-treated incidence rates. RESULTS: During the period, 24,238 patients with a diagnosis of VWD attended HTCs; for 23,479 (96.9%), VWD type was reported or could be assigned. Age-adjusted HTC-treated prevalence was 8.6 cases/100,000 (7.2/100,000 for Type 1, 1.2/100,000 for Type 2 and 1.7/million for Type 3) and was twice as high in women as men (4.8 vs. 2.4 cases/100,000) for Type 1 and similar by sex for Type 2 and Type 3. HTC-treated Type 1 incidence increased over the period, averaging nearly threefold higher for women than men (26.2 vs. 9.9/100,000 live births). Sex differences were less for Type 2 (2.2 vs. 1.4 cases/100,000 births) and slight in Type 3. CONCLUSION: Prevalence and incidence of HTC-treated VWD differ by sex and type and are likely strongly influenced by differences in rates of diagnosis. |
Evaluation of CDC's Hemophilia Surveillance Program - Universal Data Collection (1998-2011) and Community Counts (2011-2019), United States.
Schieve LA , Byams VR , Dupervil B , Oakley MA , Miller CH , Soucie JM , Abe K , Bean CJ , Hooper WC . MMWR Surveill Summ 2020 69 (5) 1-18 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. |
Hemophilia without prophylaxis: Assessment of joint range of motion and factor activity
Wang M , Recht M , Iyer NN , Cooper DL , Soucie JM . Res Pract Thromb Haemost 2020 4 (6) 1035-1045 Background: Recurrent joint bleeding in hemophilia results in arthropathy and functional impairment. The relationship of arthropathy development and factor activity (FA) has not been reported in patients with FA levels <15%-20%. Method(s): During the Centers for Disease Control and Prevention Universal Data Collection, joint range-of-motion (ROM) measurements were taken at each comprehensive visit. Data were extracted from male patients with hemophilia (PWH) age >=2 years with baseline factor activity levels <=40%, excluding those prescribed prophylaxis, and used to calculate a proportion of normal ROM (PN-ROM) measure. Data were analyzed using regression models. Result(s): There were 6703 eligible PWH with 30 102 visits. PN-ROM declined with increasing age, and was associated with hemophilia severity, race/ethnicity, obesity, and viral illnesses. PWH >=30 years old with fFA <=2% and those >=50 years old with FA <=5% had mean PN-ROM values >10% less than controls; those >=40 years old with FA <1% had values >20% less than controls. In the multivariable analysis, subjects with <1% FA had a 0.43% greater decrease (-0.49 to -0.37, 95% confidence interval) in PN-ROM each year relative to those with 16%-40% factor activity. A less pronounced effect was seen with 1%-5% or 6%-9% FA. Conclusion(s): The effect of FA on ROM loss is far greater than that of any of the other characteristics, especially with FA <10%. This emphasizes the need to maintain a high index of suspicion for arthropathy in individuals with moderate and low-mild hemophilia. |
Occurrence rates of haemophilia among males in the United States based on surveillance conducted in specialized haemophilia treatment centres
Soucie JM , Miller CH , Dupervil B , Le B , Buckner TW . Haemophilia 2020 26 (3) 487-493 INTRODUCTION: Estimates of the size and characteristics of the US haemophilia population are needed for healthcare planning and resource needs assessment. A network of comprehensive haemophilia treatment centres (HTCs) located throughout the United States receives federal support for diagnosis and management of haemophilia and other rare bleeding disorders. AIM: Estimate the incidence and prevalence of haemophilia among US males using the HTC network. METHODS: During the period 2012-2018, de-identified surveillance data were collected on all males who visited an HTC that included year of birth, gender, race, Hispanic ethnicity, residence zip code, haemophilia type and severity. Data from all patients were used to calculate period prevalence by haemophilia type, severity and state of residence. Data from a subset of patients born 1995-2014 were used to estimate incidence rates over the 20-year period. RESULTS: During the period, 21 748 males with haemophilia visited the HTCs resulting in an age-adjusted prevalence of 15.7 cases per 100 000 males (12 for haemophilia A and 3.7 for haemophilia B). Prevalence was higher among whites (15.1) than blacks (12.4) or Hispanics of either race (12.4). State-specific prevalence varied from 1.6 to 23.3 cases per 100 000. Based on 9587 males born during the index period, the average haemophilia incidence was 1 case per 4334 live male births. CONCLUSION: Based on these data, we estimate that there are between 29 761 and 32 985 males with haemophilia living in the United States today, the majority of whom receive comprehensive care in specialized clinical centres. |
Higher rates of bleeding and use of treatment products among young boys compared to girls with von Willebrand Disease
Abe K , Dupervil B , O'Brien SH , Oakley M , Kulkarni R , Gill JC , Byams V , Soucie MJ . Am J Hematol 2019 95 (1) 10-17 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 2-12 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. This article is protected by copyright. All rights reserved. |
Potential of the Community Counts registry to characterize rare bleeding disorders
Gupta S , Acharya S , Roberson C , Lail A , Soucie JM , Shapiro A . Haemophilia 2019 25 (6) 1045-1050 INTRODUCTION: Rare bleeding disorders (RBDs) comprise of heterogeneous coagulation factor deficiencies and platelet disorders that are underreported worldwide. AIM: First report on RBD data from United States haemophilia treatment center network (USHTCN). METHODS: A national surveillance system for the federally recognized USHTCN developed in collaboration with the Centers for Disease Control and Prevention (CDC) and American Thrombosis and Haemostasis Network (ATHN) was queried for patients with RBDs. Patient counts were extracted from the HTC Population Profile (HTC PP) component including limited data on patients followed through the USHTCN, and from the Registry component, including patient authorized, detailed clinical data. The prevalence of RBDs in the United States was estimated based on the HTC PP data and compared to the expected national prevalence based on data extrapolated from Orphanet, an international registry. RESULTS: Based on the estimated prevalence of RBD in the overall 2017 US population, the cases in the HTC network were lower than expected for FI, FII, FX, and FV + FVIII deficiencies by 36%, 61%, 75% and 94%, respectively, and higher than expected for FXIII, FV, FVII, and FXI deficiencies by 7%, 14%, 33% and 185%, respectively. The proportion of RBD patients reported in the HTC PP, enrolled in the Registry, was 10.8%. CONCLUSIONS: There is a clear need to identify individuals with RBDs who could benefit from the comprehensive care provided in the USHTCN. In addition, increased enrolment of people with all RBDs in the Registry is needed to improve knowledge of treatment outcomes of patients with RBDs in the United States. |
Global hemophilia care: Data for action
Soucie JM . Ann Intern Med 2019 171 (8) 585-586 Hemophilia results when mutations in either of the genes that code for the coagulant proteins factor VIII or factor IX cause abnormal blood clotting. Because these genes are located on the X chromosome, hemophilia is a sex-linked disorder that manifests primarily in males, but it can also affect females who carry the genetic defect. Variations in the mutations causing the disorder result in different levels of the affected protein, which influences bleeding tendency. The most severely affected patients have repeated bleeding, primarily into large joints, that causes chronic and disabling joint disease. Bleeding into organs and intracranial hemorrhages can lead to further disability and death. |
Origins and organization of the NHLBI State of the Science Workshop: Generating a national blueprint for future research on factor VIII inhibitors.
Sabatino DE , Pipe SW , Nugent DJ , Soucie JM , Hooper WC , Hoots WK , DiMichele DM . Haemophilia 2019 25 (4) 575-580 INTRODUCTION: The major complication of protein replacement therapy for haemophilia A is the development of anti-FVIII antibodies or inhibitors that occur in 25%-30% of persons with severe haemophilia A. Alternative therapeutics such as bypassing agents or immune tolerance induction protocols have additional challenges and are not always effective. AIM: Assemble a National Heart, Lung and Blood Institute (NHLBI) State of the Science (SOS) Workshop to generate a national blueprint for research on inhibitors to solve the problem of FVIII immunogenicity. METHODS: An Executive Steering Committee was formed in October 2017 to establish the scientific focus and Scientific Working Groups for the SOS Workshop in May 2018. Four working groups were assembled to address scientific priorities in basic, translational and clinical research on inhibitors. RESULTS: Working Group 1 was charged with determining the scientific priorities for clinical trials to include the integration of non-intravenous, non-factor therapeutics including gene therapy into the standard of care for people with haemophilia A with inhibitors. Working Group 2 established the scientific priorities for 21st-century data science and biospecimen collection for observational inhibitor cohort studies. The scientific priorities for acquiring an actionable understanding of FVIII immunogenicity and the immunology of the host response and FVIII tolerance were developed by Working Group 3. Working Group 4 designed prospective pregnancy/birth cohorts to study FVIII immunogenicity, inhibitor development and eradication. CONCLUSION: The NHLBI SOS Workshop generated a focused summary of scientific priorities and implementation strategies to overcome the challenges of eradicating and preventing inhibitors in haemophilia A. |
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
Pipe SW , Sabatino DE , Nugent DJ , Hooper WC , Soucie JM , Keith Hoots W , DiMichele DM . Haemophilia 2019 25 (4) 610-615 As elaborated by Sabatino et al,1 five decades of advances have brought us widespread availability of safe and effective haemophilia treatment. However, inhibitors, neutralizing alloantibodies to factor VIII, still occur in ~25%-30% of persons with severe haemophilia A. Within the US, it is estimated that there are over 1000 individuals with a factor VIII inhibitor.2 Inhibitors are associated with increased risk from bleeding and twice the rate of hospitalization for a bleeding complication, increased morbidity from joint disease and significantly increased rate of death due to bleeding-related causes compared to those without inhibitors. Over the last 30 years, we have gained insights on risk factors for inhibitor development from retrospective and parallel-cohort studies as well as meta-analyses.3 However, there is still much to be learned about the basic mechanisms underlying this immune response and few studies that have significantly impacted inhibitor prevention and eradication. |
Population-based surveillance of haemophilia and patient outcomes in Indiana using multiple data sources
Okolo AI , Soucie JM , Grosse SD , Roberson C , Janson IA , Allen M , Shapiro AD . Haemophilia 2019 25 (3) 456-462 INTRODUCTION: Epidemiological surveillance of haemophilia through linkage of medical records within a US state has not been conducted in 20 years. AIM: The Indiana Haemophilia Surveillance Project aims to identify all persons with haemophilia who resided in Indiana in 2011-2013 and to determine the percentage of patients in Indiana cared for at a federally recognized haemophilia treatment centre (HTC). METHODS: A retrospective review of medical charts was conducted to identify haemophilia cases during the surveillance years. Case-finding methods involved a variety of medical care resources including hospitals, administrative claims data and haematology/oncology clinic reports. RESULTS: In Indiana, 704 unique haemophilia cases were identified. Of those cases, 456 (64.8%) had factor VIII and 248 (35.2%) had factor IX deficiency. Among those with known severity levels (n = 685), 233 (34%) were severe, 185 (27%) were moderate, and 267 (39%) were mild. Overall, 81.7% of the haemophilia patients identified visited an HTC at least once during the three-year study period, which was the requirement for being considered an HTC patient. Age-adjusted prevalence for 2013 was 19.4 haemophilia cases per 100 000 males, 12.7 per 100 000 for factor VIII and 6.7 per 100 000 for factor IX. Incidence of haemophilia over the 10 years prior to the surveillance years was 1:3688 live male births in Indiana. During the surveillance years, 24 cases (3.4%) died. CONCLUSION: We observed higher incidence and prevalence of haemophilia in Indiana compared to previous national estimates, as well as higher HTC utilization among persons with haemophilia. |
The frequency of joint hemorrhages and procedures in nonsevere hemophilia A vs B
Soucie JM , Monahan PE , Kulkarni R , Konkle BA , Mazepa MA . Blood Adv 2018 2 (16) 2136-2144 Data are needed on minimal factor activity (FA) levels required to prevent bleeding in hemophilia. We aimed to evaluate associations between hemophilia type and FA level and joint bleeding and orthopedic procedures using longitudinal data. Data were collected over an 11-year period on males with nonsevere hemophilia A or B without inhibitors who were receiving on-demand factor replacement therapy. Data on the number of joint bleeds in the previous 6 months and data on procedures from clinical records were analyzed using regression models. Data were collected on 4771 patients (hemophilia A, 3315; hemophilia B, 1456) from 19 979 clinic visits. Ages ranged from 2 to 91 years and baseline FA level ranged from 1% to 49% with a mean of 9.4%. Joint bleeding rates were heterogeneous across the FA range and were highest among men age 25 to 44 years. Adjusted for FA level, the mean number of joint bleeds per 6 months was 1.4 and 0.7 for patients with hemophilia A and B, respectively (P < .001). Regression models predicted 1.4 and 0.6 bleeds per year for hemophilia A and B patients, respectively, at an FA level of 15%. Patients with hemophilia B were 30% less likely than those with hemophilia A to have undergone an orthopedic procedure. We conclude that joint bleed rates for any given FA level were higher among hemophilia A than hemophilia B patients, and target FA levels of 15% are unlikely to prevent all joint bleeding in US males with hemophilia. |
Risk factors associated with invasive orthopaedic interventions in males with haemophilia enrolled in the Universal Data Collection program from 2000 to 2010
Tobase P , Lane H , Siddiqi AE , Soucie JM , Ingram-Rich R , Ward S , Gill JC . Haemophilia 2018 24 (6) 964-970 BACKGROUND: Invasive orthopaedic interventions (IOI) are often used to control recurrent haemarthrosis, pain and loss of joint function, in males with haemophilia (Factor VIII and Factor IX deficiency). AIM: Identify risk factors associated with IOIs in males with haemophilia enrolled in the Universal Data Collection (UDC) surveillance program from 2000 until 2010. METHODS: Data were collected on IOIs performed on patients receiving care in 130 haemophilia treatment centers in the United States annually by health care providers using standardized forms. IOIs included in this study are as follows: 1) synovectomy and 2) arthrodesis or arthroplasty (A/A). Information about potential risk factors was obtained from the preceding UDC visit if available, or from the same visit if not. Patients with no reported IOI at any of their UDC visits were the reference group for the analysis. Multivariate analyses were conducted to identify independent risk factors for synovectomies and arthrodesis/arthroplasty. RESULTS: Risk factors significantly associated with the two IOI categories were age, student status, haemophilia severity, number of joint bleeds within the last 6 months, HIV or hepatitis C (HCV) status. Multivariate analyses showed patients on continuous prophylaxis were 50% less likely to have had a synovectomy and were 40% less likely to have an A/A. CONCLUSIONS: This study shows modifiable risk factors, including management of bleeding episodes with a continuous prophylactic treatment schedule are associated with a decreased likelihood of IOIs in males with haemophilia. |
Relevance of abusive head trauma to intracranial hemorrhages and bleeding disorders
Anderst JD , Carpenter SL , Presley R , Berkoff MC , Wheeler AP , Sidonio RF Jr , Soucie JM . Pediatrics 2018 141 (5) BACKGROUND: Bleeding disorders and abusive head trauma (AHT) are associated with intracranial hemorrhage (ICH), including subdural hemorrhage (SDH). Because both conditions often present in young children, the need to screen for bleeding disorders would be better informed by data that include trauma history and are specific to young children. The Universal Data Collection database contains information on ICH in subjects with bleeding disorders, including age and trauma history. Study objectives were to (1) characterize the prevalence and calculate the probabilities of any ICH, traumatic ICH, and nontraumatic ICH in children with congenital bleeding disorders; (2) characterize the prevalence of spontaneous SDH on the basis of bleeding disorder; and (3) identify cases of von Willebrand disease (vWD) that mimic AHT. METHODS: We reviewed subjects <4 years of age in the Universal Data Collection database. ICH was categorized on the basis of association with trauma. Prevalence and probability of types of ICH were calculated for each bleeding disorder. RESULTS: Of 3717 subjects, 255 (6.9%) had any ICH and 206 (5.5%) had nontraumatic ICH. The highest prevalence of ICH was in severe hemophilia A (9.1%) and B (10.7%). Of the 1233 subjects <2 years of age in which the specific location of any ICH was known, 13 (1.1%) had spontaneous SDH (12 with severe hemophilia; 1 with type 1 vWD). The findings in the subject with vWD were not congruent with AHT. CONCLUSIONS: In congenital bleeding disorders, nontraumatic ICH occurs most commonly in severe hemophilia. In this study, vWD is not supported as a "mimic" of AHT. |
Prophylaxis use among males with haemophilia B in the United States
Ullman M , Zhang QC , Grosse SD , Recht M , Soucie JM . Haemophilia 2017 23 (6) 910-917 INTRODUCTION: Prophylaxis is considered the optimal treatment for persons with moderate to severe haemophilia (factor activity between 1-5% of normal and <1% of normal respectively) in countries where safe factor concentrates are available and economically feasible. Historically, prophylactic treatment has not been well studied in the haemophilia B (HB) population due to difficulties in obtaining a sufficiently large sample. AIM: This study examines the prevalence of prophylaxis use among a robust sample of persons with HB in the United States and its association with specific demographic and clinical characteristics. METHODS: Using data collected between 1998 and 2011 for the Centers for Disease Control and Prevention's Universal Data Collection project, we analysed data on 2428 males with moderate to severe HB aged 2-79 years who were seen at 135 federally funded haemophilia treatment centres. RESULTS: Prevalence of prophylactic treatment in our sample was 35% among children and youth (ages 2-19) and 14% among adults (age 20 and older). Increased HB prophylaxis use was significantly associated with younger age (<40 years), Hispanic ethnicity, severe disease and self-infusion, while decreased use was associated with above-normal body mass index (BMI) in adults. Health care coverage was vital, although type of coverage did not appear to influence access. CONCLUSIONS: Our analysis confirms previous reports of lower prevalence of prophylaxis use among individuals with HB compared to those with haemophilia A and adds to the body of knowledge regarding treatment patterns among a historically understudied population. |
The effects of joint disease, inhibitors and other complications on health-related quality of life among males with severe haemophilia A in the United States
Soucie JM , Grosse SD , Siddiqi AE , Byams V , Thierry J , Zack MM , Shapiro A , Duncan N . Haemophilia 2017 23 (4) e287-e293 INTRODUCTION: Health-related quality of life (HRQoL) is reduced among persons with haemophilia. Little is known about how HRQoL varies with complications of haemophilia such as inhibitors and joint disease. Estimates of preference-based HRQoL measures are needed to model the cost-effectiveness of prevention strategies. AIM: We examined the characteristics of a national sample of persons with severe haemophilia A for associations with two preference-based measures of HRQoL. METHODS: We analysed utility weights converted from EuroQol 5 Dimensions (EQ-5D) and the Short Form 6 Dimensions (SF-6D) scores from 1859 males aged ≥14 years with severe haemophilia A treated at 135 US haemophilia treatment centres in 2005-2011. Bivariate and regression analyses examined age-group-specific associations of HRQoL with inhibitor status, overweight/obesity, number of bleeds, viral infections, indicators of liver and joint disease, and severe bleeding at the time of the first HRQoL measurement. RESULTS: Overall mean HRQoL utility weight values were 0.71 using the SF-6D and 0.78 using the EQ-5D. All studied patient characteristics except for overweight/obesity were significantly associated with HRQoL in bivariate analyses. In a multivariate analysis, only joint disease was significantly associated with utility weights from both HRQoL measures and across all age groups. After adjustment for joint disease and other variables, the presence of an inhibitor was not significantly associated with HRQoL scores from either of the standardized assessment tools. CONCLUSION: Clinically significant complications of haemophilia, especially joint disease, are strongly associated with HRQoL and should be accounted for in studies of preference-based health utilities for people with haemophilia. |
Prophylaxis usage, bleeding rates and joint outcomes of hemophilia 1999 - 2010: a surveillance project
Manco-Johnson MJ , Soucie JM , Gill JC . Blood 2017 129 (17) 2368-2374 This analysis of the United States Hemophilia Treatment Center Network and the Centers for Disease Control and Prevention surveillance registry assessed trends in prophylaxis use and its impact on key indicators of arthropathy across the life span among participants with severe hemophilia A. Data on demographics, clinical characteristics and outcomes were collected prospectively between 1999 and 2010 at annual clinical visits to 134 hemophilia treatment centers. Trends in treatment and outcomes were evaluated using cross-sectional and longitudinal analyses. Data analyzed included 26,614 visits for 6,196 males, mean age at first registry visit 17.7 years, median 14, range 2 to 69. During this time, prophylaxis use increased from 31% to 59% overall, with 75% of children and youths less than 20 years on prophylaxis by 2010. On cross-sectional analysis bleeding rates decreased dramatically for the entire population (p< 0.001) in parallel with increased prophylaxis usage, possibly as frequent bleeders adopted prophylaxis. Joint bleeding decreased proportionately with prophylaxis (22%) and non-prophylaxis (23%); target joints decreased more with prophylaxis (80% vs. 61%). Joint, total and target joint bleeding on prophylaxis were 33%, 41% and 27%, respectively, compared to non-prophylaxis. On longitudinal analysis of individuals over time, prophylaxis predicted decreased bleeding at any age (p < 0.001), but only prophylaxis initiation prior to age 4 years and non-obesity predicted preservation of joint motion (p<0.001 for each). Using a national registry care providers in a specialized health care network for a rare disorder were able to detect and track trends in outcomes over time. |
Accounting for differences in healthcare utilization and expenditures among US males with haemophilia by type of health insurance
Guh S , Grosse SD , Ullman M , Soucie JM . Haemophilia 2017 23 (2) e147-e151 We previously published analyses of average health care expenditures during 2008 for US males with haemophilia. We reported that average annual health-care expenditures were $100 000 to $155 000 in 2008 US dollars [1,2]. In this research letter, we report further analyses from the MarketScan® research databases intended to help understand differences in expenditures for those covered by either Medicaid or employer-sponsored insurance (ESI). | Our primary measures of healthcare utilization are proportion of admission, proportion of treat-and-release ED visits (hereafter referred to as ED visits), length of hospital stays, frequency of ED visits and frequency of non-ED outpatient visits. Length of stay for hospitalizations is determined from admission and discharge dates. ED visits that resulted in hospital admission are recorded as hospitalizations. Outpatient visits are defined as visits based on outpatient claims data, except ED visits and claims filed by laboratories, imaging centres, radiologists, pathologists, pharmacists, supply centres, case managers and home health-care services. |
Measuring the quality of haemophilia care across different settings: A set of performance indicators derived from demographics data
Iorio A , Stonebraker JS , Brooker M , Soucie JM . Haemophilia 2016 23 (1) e1-e7 BACKGROUND: Haemophilia is a rare disease for which quality of care varies around the world. We propose data-driven indicators as surrogate measures for the provision of haemophilia care across countries and over time. MATERIALS AND METHODS: The guiding criteria for selection of possible indicators were ease of calculation and direct applicability to a wide range of countries with basic data collection capacities. General population epidemiological data and haemophilia A population data from the World Federation of Hemophilia (WFH) Annual Global Survey (AGS) for the years 2013 and 2010 in a sample of 10 countries were used for this pilot exercise. RESULTS: Three indicators were identified: (i) the percentage difference between the observed and the expected haemophilia A incidence, which would be close to null when all of the people with haemophilia A (PWHA) theoretically expected in a country would be known and reported to the AGS; (ii) the percentage of the total number of PWHA with severe disease; and (iii) the ratio of adults to children among PWHA standardized to the ratio of adults to children for males in the general population, which would be close to one if the survival of PWHA is equal to that of the general population. Country-specific values have been calculated for the 10 countries. CONCLUSIONS: We have identified and evaluated three promising indicators of quality of care in haemophilia. Further evaluation on a wider set of data from the AGS will be needed to confirm their value and further explore their measurement properties. |
Complications of haemophilia in babies (first two years of life): a report from the Centers for Disease Control and Prevention Universal Data Collection System
Kulkarni R , Presley RJ , Lusher JM , Shapiro AD , Gill JC , Manco-Johnson M , Koerper MA , Abshire TC , DiMichele D , Hoots WK , Mathew P , Nugent DJ , Geraghty S , Evatt BL , Soucie JM . Haemophilia 2016 23 (2) 207-214 AIM: To describe the prevalence and complications in babies ≤2 years with haemophilia. METHODS: We used a standardized collection tool to obtain consented data on eligible babies aged ≤2 years with haemophilia enrolled in the Centers for Disease Control and Prevention Universal Data Collection System surveillance project at US Hemophilia Treatment Centers (HTCs). RESULTS: Of 547 babies, 82% had haemophilia A, and 70% were diagnosed within one month of birth. Diagnosis was prompted by known maternal carrier status (40%), positive family history (23%), bleeding (35%) and unknown 2%; 81% bled during the first two years. The most common events were bleeding (circumcision, soft tissue, oral bleeding) and head injury. There were 46 episodes of intracranial haemorrhage (ICH) in 37 babies (7%): 18 spontaneous, 14 delivery related, 11 traumatic, 2 procedure related and 1 unknown cause. Of the 176 central venous access devices (CVADs) in 148 (27%) babies, there were 137 ports, 22 surgically inserted central catheters and 20 peripherally inserted central catheters. Ports had the lowest complication rates. Inhibitors occurred in 109 (20%) babies who experienced higher rates of ICH (14% vs. 5%; P = 0.002), CVAD placement (61% vs. 19%; P < 0.001) and CVAD complications (44% vs. 26%; P < 0.001). The most common replacement therapy was recombinant clotting factor concentrates. CONCLUSION: Bleeding events in haemophilic babies ≤2 years were common; no detectable difference in the rates of ICH by the mode of delivery was noted. Neonatal factor exposure did not affect the inhibitor rates. Minor head trauma, soft tissue and oropharyngeal bleeding were the leading indications for treatment. |
NHF-McMaster guideline on care models for haemophilia management
Pai M , Key NS , Skinner M , Curtis R , Feinstein M , Kessler C , Lane SJ , Makris M , Riker E , Santesso N , Soucie JM , Yeung CH , Iorio A , Schunemann HJ . Haemophilia 2016 22 Suppl 3 6-16 This guideline was developed to identify evidence-based best practices in haemophilia care delivery, and discuss the range of care providers and services that are most important to optimize outcomes for persons with haemophilia (PWH) across the United States. The guideline was developed following specific methods described in detail in this supplement and based on the GRADE (Grading of Recommendations, Assessment, Development and Evaluation approach). Direct evidence from published literature and the haemophilia community, as well as indirect evidence from other chronic diseases, were reviewed, synthesized and applied to create evidence-based recommendations. The Guideline panel suggests that the integrated care model be used over non-integrated care models for PWH (conditional recommendation, moderate certainty in the evidence). For PWH with inhibitors and those at high risk for inhibitor development, the same recommendation was graded as strong, with moderate certainty in the evidence. The panel suggests that a haematologist, a specialized haemophilia nurse, a physical therapist, a social worker and round-the-clock access to a specialized coagulation laboratory be part of the integrated care team, over an integrated care team that does not include all of these components (conditional recommendation, very low certainty in the evidence). Based on available evidence, the integrated model of care in its current structure, is suggested for optimal care of PWH. There is a need for further appropriately designed studies that address unanswered questions about specific outcomes and the optimal structure of the integrated care delivery model in haemophilia. |
Care models in the management of haemophilia: A systematic review
Yeung CH , Santesso N , Pai M , Kessler C , Key NS , Makris M , Navarro-Ruan T , Soucie JM , Schunemann HJ , Iorio A . Haemophilia 2016 22 Suppl 3 31-40 BACKGROUND: Haemophilia care is commonly provided via multidisciplinary specialized management. To date, there has been no systematic assessment of the impact of haemophilia care delivery models on patient-important outcomes. OBJECTIVE: To conduct a systematic review of published studies assessing the effects of the integrated care model for persons with haemophilia (PWH). SEARCH METHODS: We searched MEDLINE, EMBASE and CINAHL up to April 22, 2015, contacted experts in the field, and reviewed reference lists. SELECTION CRITERIA: Randomized and non-randomized studies of PWH or carriers, focusing mainly on the assessment of care models on delivery. DATA COLLECTION AND ANALYSIS: Two investigators independently screened title, abstract, and full text of retrieved articles for inclusion. Risk of bias and overall quality of evidence was assessed using Cochrane's ACROBAT-NRSI tool and GRADE respectively. Relative risks, mean differences, proportions, and means and their variability were calculated as appropriate. RESULTS: 27 non-randomized studies were included: eight comparative and 19 non-comparative studies. We found low- to very low-quality evidence that in comparison to other models of care, integrated care may reduce mortality, hospitalizations and emergency room visits, may lead to fewer missed days of school and work, and may increase knowledge seeking. CONCLUSION: Our comprehensive review found low- to very low-quality evidence from a limited number of non-randomized studies assessing the impact of haemophilia care models on some patient-important outcomes. While the available evidence suggests that adoption of the integrated care model may provide benefit to PWH, further high-quality research in the field is needed. |
Men with severe hemophilia in the United States: birth cohort analysis of a large national database
Mazepa MA , Monahan PE , Baker JR , Riske BK , Soucie JM . Blood 2016 127 (24) 3073-81 The availability of longitudinal data collected prospectively from 1998 to 2011 at federally funded United States hemophilia treatment centers (U.S. HTCs) provided an opportunity to construct a descriptive analysis of how outcomes of men with severe hemophilia have been altered by the incremental advances and setbacks in hemophilia care in the last 50 years in the U.S. This surveillance collaboration with the U.S. Centers for Disease Control and Prevention assembled the largest uniformly examined population with severe hemophilia (n = 4,899 men with severe factor VIII and IX deficiency). To address the heterogeneity of this population, four successive birth cohorts, differentially affected by "eras" of hemophilia care, were examined separately in regards to demographics, complications of hemophilia and its treatment, and mortality. Severely affected men in each birth cohort were compared also to the corresponding mild hemophilia birth cohorts (n = 2587 men total) to control for outcomes that might be attributable to aging and environment independent of severely defective hemostasis. The analysis demonstrates improving access to standard of care therapy, correlating the proportion of men on prophylactic factor replacement and reduced bleeding frequency for the youngest men. Frequent bleeding persisted in one third to one half of men across all ages, however, and the disability gap between severe and mild hemophilia did not narrow. The greatest cause of death was liver failure but attempted anti-hepatitis C virus therapy and cure were low. The study suggests a continued need for national surveillance to monitor and inform hemophilia interventions and outcomes. |
Achievements, challenges and unmet needs for haemophilia patients with inhibitors: Report from a symposium in Paris, France on 20 November 2014.
Dargaud Y , Pavlova A , Lacroix-Desmazes S , Fischer K , Soucie M , Claeyssens S , Scott DW , d'Oiron R , Lavigne-Lissalde G , Kenet G , Escuriola Ettingshausen C , Borel-Derlon A , Lambert T , Pasta G , Negrier C . Haemophilia 2016 22 Suppl 1 1-24 Over the past 20 years, there have been many advances in haemophilia treatment that have allowed patients to take greater control of their disease. However, the development of factor VIII (FVIII) inhibitors is the greatest complication of the disease and a challenge in the treatment of haemophilia making management of bleeding episodes difficult and surgical procedures very challenging. A meeting to discuss the unmet needs of haemophilia patients with inhibitors was held in Paris on 20 November 2014. Topics discussed were genetic and non-genetic risk factors for the development of inhibitors, immunological aspects of inhibitor development, FVIII products and inhibitor development, generation and functional properties of engineered antigen-specific T regulatory cells, suppression of immune responses to FVIII, prophylaxis in haemophilia patients with inhibitors, epitope mapping of FVIII inhibitors, current controversies in immune tolerance induction therapy, surgery in haemophilia patients with inhibitors and future perspectives for the treatment of haemophilia patients with inhibitors. A summary of the key points discussed is presented in this paper. |
Characteristics of hemophilia patients with factor VIII inhibitors detected by prospective screening
Miller CH , Rice AS , Boylan B , Payne AB , Kelly FM , Escobar MA , Gill J , Leissinger C , Soucie JM . Am J Hematol 2015 90 (10) 871-6 PURPOSE: To characterize patients with inhibitors identified by prospective screening. FINDINGS: In a prospective study at 17 hemophilia centers with central inhibitor measurement by Nijmegen-Bethesda assay, 23 (2.8%) of 824 hemophilia A patients had new inhibitors detected: 9 high-titer inhibitors (HTI: 7 ≥5.0 NBU plus 2 of 2.6 and 3.4 NBU at immune tolerance induction initiation) and 14 low-titer inhibitors (LTI: 0.5-1.9 NBU). HTI occurred at an earlier age (median 2 years, range 1-18, vs. median 11 years, range 2-61, p=0.016). Both HTI (22%) and LTI (43%) occurred in non-severe patients. All HTI, but only 64% of LTI, were found to be FVIII-specific by chromogenic Bethesda assay or fluorescence immunoassay (FLI), indicating a high rate of false-positive LTI. Repeat specimens confirmed all HTI, 7/9 LTI, and 7/7 FVIII-specific LTI. FLI results were similar between HTI and FVIII-specific LTI; all included IgG1 and IgG4 subclasses. A comparable prospective study conducted from 1975-9 at 13 U.S. centers found 31 (2.3%) new inhibitors among 1360 patients. In both studies, one-third of inhibitors occurred in non-severe patients and one-quarter after 150 exposure days (ED). Significant differences were seen in the age at which inhibitors occurred (median 16 years in the older study vs. 5 years in the current study, p=0.024) and in ED prior to inhibitor development, 10% in the older study and 43% in the current study occurring within 0-20 ED. CONCLUSIONS: Prospective screening detects Inhibitors in patients of all severities, ages, and ED. Some LTI, however, are false positives. |
Cluster of inhibitors among adult inpatients with haemophilia in a single institution
Ishaku NG , Key NS , Miller CH , Nielsen B , Buckner T , Chen SL , Hooper WC , Soucie JM . Haemophilia 2015 21 (4) e325-8 In June 2012, an academic haematologist in a tertiary health facility notified the Centers for Disease Control and Prevention (CDC) of new onset inhibitors during hospitalization in four previously treated people with haemophilia (PWH). The four patients were considered at low risk for this complication. Inhibitor onset occurred among patients hospitalized during a 14-month period, whereas no inhibitor cases had occurred among inpatients during the previous 12-month period. All four cases had received a recombinant clotting factor concentrate (CFC) from a single manufacturer, raising concern about a possible product-related issue. The situation was reported to the North Carolina Department of Health and Human Services who advised that an investigation be carried out and requested assistance from CDC. | This report summarizes the results of the investigation conducted with the following specific aims: (i) to determine whether the cases represented an increase in the baseline inhibitor incidence among inpatients with haemophilia at the index facility; (ii) to assess whether the cases were at greater risk for an inhibitor than other inpatients with haemophilia as a result of personal, clinical or treatment factors; and (iii) to evaluate the possible influence of changes in hospital practices related to CFC use during the period. |
Impact of inhibitors on hemophilia A mortality in the United States
Walsh CE , Soucie JM , Miller CH . Am J Hematol 2015 90 (5) 400-5 The previously published mortality studies are limited in hemophilia populations but suggest that there is no increased risk of mortality in factor VIII inhibitor patients. This retrospective study analyzed surveillance data collected on 7,386 males with severe hemophilia A over a 13-year period to assess the association between a current inhibitor and death. During the study period, 432 participants died, among whom 48 were patients with an inhibitor. Clinical characteristics most strongly associated with death were increased number of reported bleeds, signs of liver disease, infection with either HIV or HCV, and the presence of inhibitor. Patients who underwent successful tolerization were not considered inhibitor patients in our analysis. In a multivariable analysis, the odds of death were 70% higher among patients with a current inhibitor compared to those without an inhibitor (P < 0.01). Deaths among patients with inhibitors were much more likely to be attributed to bleeding complications than those among patients without an inhibitor (42 vs. 12%, P < 0.0001). We conclude that males with severe hemophilia A and a current inhibitor are at increased risk of death. |
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