National needs assessment of patients treated at the United States Federally-Funded Hemophilia Treatment Centers.

AIM: The National Hemophilia Program Coordinating Center, with the U.S. Regional Hemophilia Network conducted a national needs assessment of U.S. Hemophilia Treatment Center (HTC) patients. The objectives were to determine: (i) To what extent do patients report that they receive needed services and education; (ii) How well do the services provided meet their needs; and (iii) What are the patients' perspectives about their care. METHODS: A survey was mailed to active patients of 129 HTCs. Respondents completed the anonymous surveys on line or returned them by mail. Questions focused on management and information, access and barriers to care, coping, resources, and transition. RESULTS: Of 24 308 questionnaires mailed, 4004 (16.5%) were returned. Most respondents reported very few gaps in needed services or information and reported that services and information met their needs. Over 90% agreed or strongly agreed that care was patient-centred and rated HTC care as important or very important. Identified gaps included dietary advice, genetic testing, information on ageing, sexual health and basic needs resources. Minority respondents reported more barriers. CONCLUSION: This survey is the largest assessment of the HTC population. Respondents reported that the services and information provided by the HTCs met their needs. Quality improvement opportunities include transition and services related to ageing and sexual health. Further investigation of barriers to care for minorities is underway. Results will help develop national priorities to better serve all patients in the US. HTCs.

US Hemophilia Treatment Center population trends 1990-2010: patient diagnoses, demographics, health services utilization.

For several decades, US government agencies have partially supported regional networks of Hemophilia Treatment Centers (HTC). HTC multidisciplinary teams provide comprehensive and coordinated diagnosis, treatment, prevention, education, outreach and surveillance services to improve the health of people with genetic bleeding disorders. However, national data are scarce on HTC-patient population trends and services. The aim of the study was to examine national trends over the past 20 years in patient diagnoses, demographics and health services utilization among the Health Resources and Services Administration (HRSA) and Centers for Disease Control and Prevention (CDC)-supported HTC network. Diagnoses, demographics and health services utilization data from 1990 to 2010 were aggregated from all HTCs using the Hemophilia Data Set (HDS). From 1990 to 2010, the HTC population grew 90% from 17 177 to 32 612. HTC patients with von Willebrand's disease increased by 148%, females by 346%, Hispanic patients by 236% and African Americans by 104%. Four thousand and seventy-five deaths were reported. From 2002 to 2010, annual comprehensive evaluations grew 38%, and persons with severe haemophilia on a home intravenous therapy programme rose 37%. In 2010, 46% of patients were less than 18 years vs. 24% for the general US population. The Hemophilia Data Set documents the growth and diversity of the US Hemophilia Treatment Center Network's patient population and services. Despite disproportionate deaths due to HIV, the HTC patient base grew faster than the general US population. The HDS is a vital national public health registry for this rare-disorder population.

Quality of life in haemophilia A: Hemophilia Utilization Group Study Va (HUGS-Va).

This study describes health-related quality of life (HRQoL) of persons with haemophilia A in the United States (US) and determines associations between self-reported joint pain, motion limitation and clinically evaluated joint range of motion (ROM), and between HRQoL and ROM. As part of a 2-year cohort study, we collected baseline HRQoL using the SF-12 (adults) and PedsQL (children), along with self-ratings of joint pain and motion limitation, in persons with factor VIII deficiency recruited from six Haemophilia Treatment Centres (HTCs) in geographically diverse regions of the US. Clinically measured joint ROM measurements were collected from medical charts of a subset of participants. Adults (N = 156, mean age: 33.5 ± 12.6 years) had mean physical and mental component scores of 43.4 ± 10.7 and 50.9 ± 10.1, respectively. Children (N = 164, mean age: 9.7 ± 4.5 years) had mean total PedsQL, physical functioning, and psychosocial health scores of 85.9 ± 13.8, 89.5 ± 15.2, and 84.1 ± 15.3, respectively. Persons with more severe haemophilia and higher self-reported joint pain and motion limitation had poorer scores, particularly in the physical aspects of HRQoL. In adults, significant correlations (P < 0.01) were found between ROM measures and both self-reported measures. Except among those with severe disease, children and adults with haemophilia have HRQoL scores comparable with those of the healthy US population. The physical aspects of HRQoL in both adults and children with haemophilia A in the US decrease with increasing severity of illness. However, scores for mental aspects of HRQoL do not differ between severity groups. These findings are comparable with those from studies in European and Canadian haemophilia populations.

Promoting safer sex among HIV-positive youth with haemophilia: theory, intervention, and outcome.

The goal of the project was to develop and evaluate theory-based interventions designed to change sexual behaviour and promote safer sex practices of HIV seropositive young men and adolescents with haemophilia to prevent transmission to sexual partners and offspring. Safer sex was defined as abstinence, consistent condom use, or 'outercourse' (intimate, non-intercourse sexual behaviour). This project utilized the Transtheoretical Model developed by Prochaska and DiClemente, which describes behaviour change as an incremental, stage-based process. The 1-year intervention protocol consisted of two individual sessions and two peer-centred activities. One hundred and four adolescents, residing in 22 states, participated. Pre- and post-intervention evaluations were conducted to measure stage progression for participants. The number who were in the action or maintenance stage of change for safer sex was significantly greater at post-test than at pre-test (79 vs. 62%, P < 0.0001). Participants also reported an increased use of outercourse. In addition, significant increases in self-efficacy and knowledge regarding safer sex were demonstrated. Following these stage-based interventions, participants were significantly more likely to be engaging in safer sex behaviours than they were previously. These intervention activities can be adapted for use with other adolescent populations and for other behaviour change goals in adolescents with haemophilia.

Sexual behavior change among human immunodeficiency virus-infected adolescents with hemophilia. Adolescent Hemophilia Behavioral Intervention Evaluation Project Study Group.

PURPOSE: To determine the factors associated with the adoption or maintenance of consistent safer sexual behaviors among human immunodeficiency virus-positive adolescents and young adults with hemophilia. METHODS: One hundred eleven adolescents at 10 hemophilia care sites participated in an intervention program designed to increase safer sexual behaviors (abstinence, condom use, or nonpenetrative behavior). The theory-based intervention spanned 1 year. Adolescents attended individual sessions, small group activities, and an intensive group retreat. RESULTS: Patients who maintained or improved safer sexual behaviors were compared with those who relapsed or did not improve. Logistic regression analyses found that improvement and maintenance of safer sexual behavior were significantly associated with perceived peer support for outercourse (odds ratio [OR]: 5.47; confidence interval [CI]: 1.4-20.8), perceived peer support for abstinence (OR: 5.08; CI: 1.2-20.1), and decreased general emotional distress (OR: 4.65; CI: 1.04-20.6). Perceived health status and previous sexual behavior were unrelated to change in safer sexual behavior. CONCLUSIONS: These longitudinal data indicate that improvement and maintenance of safer sexual behavior among adolescents during an intervention is strongly associated with perceptions of peer support for safer sex and lesser degrees of emotional distress. Programs for human immunodeficiency virus-infected adolescents may require developmentally appropriate social and psychological approaches to impact peer norms and emotional well-being.

Issues of disclosure and condom use in adolescents with hemophilia and HIV. Hemophilia Behavioral Evaluative Intervention Project Staff.

PURPOSE: To examine the patterns, facilitators, and barriers to disclosure of HIV seropositivity in an adolescent population and to determine the relationship between disclosure and condom use. BACKGROUND: In recent years, public health efforts have focused on methods to prevent the transmission of the Human Immunodeficiency Virus (HIV). These efforts have included safer sex education, skill building and self-efficacy training, behavioral change techniques, and encouragement of serostatus disclosure to sexual partners. In 1990, the Centers for Disease Control and Prevention (CDC) funded 10 hemophilia treatment centers to develop and implement a theory-based behavioral intervention to prevent the sexual transmission of HIV. METHODS: A baseline survey, focusing on barriers to safer sex, the influence of parents, peers, and sexual partners, alcohol and drug use, and communication and disclosure patterns, was administered to 321 young males (ages 12 to 25) with hemophilia and HIV. RESULTS: Fifty-eight percent of the sexually experienced adolescents did not disclose their HIV status to their most recent sexual partners (i.e., nondisclosers) compared to 42 percent who reported that either they informed their partners or their partners already knew their HIV status (i.e., disclosers). There was no correlation between disclosure and condom use. The most significant predictor of disclosure was the perception that peers would disclose their HIV status. CONCLUSION: The results suggest that disclosure does not necessarily facilitate condom use in this population. This conclusion may have implications for future public health efforts in HIV prevention. Rather than focusing primarily on the promotion of serostatus disclosure, behavioral interventions should emphasize the practice of safer sex, utilizing peer educators and support networks.

Maintaining safer sex behaviours in HIV-infected adolescents with haemophilia. The Hemophilia Behavioral Evaluative Intervention Project Committee.

Adolescents with haemophilia comprise 44% of the reported AIDS cases in teenagers. Unprotected sexual intercourse among this group increases the risk of HIV transmission. Understanding the influences which others may have on the sexual behaviour of adolescents with HIV and haemophilia may lead to the development of effective risk reduction strategies. An evaluative instrument, administered to 307 HIV-infected adolescents with haemophilia, assessed their behavioural stage of change (Prochaska & DiClemente), attitudes, beliefs and behaviours about safer sex practices. The influence of parents, peers and sexual partners on sexual behaviour was compared between (1) those who were sexually experienced and (2) and those who were sexually inexperienced. Barriers and facilitators to practising safer sex were identified. Although parents influenced the sexual behaviour of both groups, this influence was significantly greater in the sexually inactive group. Fewer than 20% reported that their peers impacted their decisions about sexual behaviour. Eighty-six per cent of the sexually active indicated that partners significantly impacted their sexual decisions, while 60% of the sexually inactive indicated that future partners would affect their decisions about sex. Most participants agreed that disclosure of HIV status before intercourse was desirable, but only 31% of the sexually active said they told every partner. Fear of rejection or a negative reaction from the partner, and lack of communication skills were the greatest barriers to disclosure of HIV status and practising safer sex. This study indicates that behavioural interventions for both groups should focus on developing communication skills and self-efficacy. Interventions should include the key influences for each group--parents for the sexually inactive and partners for the sexually active.

Substance use, coping, and safer sex practices among adolescents with hemophilia and human immunodeficiency virus. The Hemophilia Behavioral Intervention Evaluative Project Committee.

PURPOSE: To examine the use of alcohol and other drugs (AOD) to cope with the human immunodeficiency virus (HIV), the use of AOD before or during sex by 306 adolescent males with HIV and hemophilia, and its association with safer sex practices. METHODS: A survey instrument was administered to adolescents at 11 sites of the Hemophilia Behavioral Intervention Evaluative Project. Survey questions focused on knowledge of sexual activity, safer sex practices, AOD use, attitudinal and behavioral influences of parents, peers and sex partners, communication patterns, and perceived facilitators and barriers to practicing safer sex. RESULTS: A total of 68% of all respondents reported using condoms every time they had heterosexual sex. Respondents who did not use AOD to cope were more likely than AOD copers to report that they disclose their HIV status to all sex partners, talk to all of their sex partners about safer sex, find the use of condoms more enjoyable, and have sex partners who approved of their use of condoms. Condom use was not related to the use of AOD to cope or the use of AOD with the most recent female sex partner. CONCLUSIONS: The use of AOD to cope with HIV and its use before or during sex was negatively associated with certain safer sex attitudes and practices. AOD use may help facilitate HIV transmission among adolescents with HIV and/or hemophilia.

The low risk of hepatitis C virus transmission among sexual partners of hepatitis C-infected hemophilic males: an international, multicenter study.

To study the transmission rate of hepatitis C virus (HCV) in the female sexual partners of antibody-positive hemophilic males, 106 partners from three hemophilia centers located in Europe, America, and Australia were tested for HCV seropositivity using a first-generation enzyme-linked immunosorbent assay (ELISA-1) and, subsequently, a second-generation ELISA (ELISA-2) and a supplemental recombinant immunoblot assay. Additionally, the cohort was tested for the presence of antibody to the human immunodeficiency virus type-1 and hepatitis B virus markers. No female partner was HCV antibody-positive using the ELISA-1 test, whereas five were seropositive by the ELISA-2 test. Three of these five female partners were seropositive on the supplemental test, the remaining two having indeterminate results, for an overall prevalence of 2.7%. Thus, even with the use of sensitive testing, the prevalence of HCV infection remains low in this cohort, showing that the efficiency of heterosexual transmission of HCV is poor.

Pregnancy in a cohort of long-term partners of human immunodeficiency virus-seropositive hemophiliacs.

Since 1981, there have been 17 pregnancies in 12 long-term female sexual partners of human immunodeficiency virus (HIV-1)-seropositive hemophilic men at the New England Hemophilia Center. Eleven of 12 women were seronegative for HIV antibody and one was seropositive. Six of the women followed a specific antibody testing schedule for nine pregnancies. This involved antibody testing at specific points before, during, and after pregnancy. All of the seronegative women had at least one negative antibody test at the conclusion of each pregnancy. Fourteen of 16 pregnancies in the seronegative women resulted in live-born infants. The children now range in age from 7 months to 7 years and 8 months, and have no significant medical problems. The woman found to be seropositive at 8 weeks' gestation of her first pregnancy subsequently delivered an infected infant. In this small group, 11 of 12 women at risk for HIV transmission were able to become pregnant and remain seronegative for HIV antibody. Antibody testing during pregnancy gave the women information on which to base reproductive choices.

Prevalence of hepatitis C virus antibody in a cohort of hemophilia patients.

One hundred thirty-one patients followed at the New England Hemophilia Center (Worcester, MA) were tested for antibody to hepatitis C virus (HCV). All but two had used factor concentrate that had not undergone viral inactivation; two patients had used only cryoprecipitate. The overall prevalence of HCV antibody positivity was 76.3%. There was no significant difference in age or the amount of non-heat-treated factor concentrate used between the group that was HCV antibody positive and negative. There was also no significant difference between aminotransferase levels in the two groups. There was a positive association between HCV antibody and the presence of antibody to hepatitis B core antigen and antibody to human immunodeficiency virus. A group of 31 patients were tested twice for HCV antibody at intervals of 35 to 71 months. In this subset, 25 were repeatedly seropositive, 4 were repeatedly seronegative, and 2 went from seropositive to seronegative. These data confirm the previous impression that non-A, non-B hepatitis is a major sequela to the use of pooled coagulation factor concentrates. HCV infection may account for most of the chronic liver disease observed in this population. Anti-HCV testing of plasma donors and improved methods of viral inactivation should prevent new cases from developing.

The use of porcine factor VIII concentrate (Hyate:C) in the treatment of patients with inhibitor antibodies to factor VIII. A multicenter US experience.

The response to a highly purified concentrate of porcine factor VIII was evaluated in 45 bleeding episodes in 38 patients with high responding inhibitor antibodies to factor VIII. A total of 437 infusions were given. The patients came from 25 hemophilia centers in the United States. The majority had a life- or limb-threatening hemorrhage for which other modalities had not been successful. In 32 of 45 episodes, a good to excellent response was obtained. Adverse reactions were minimal, occurring in 17 treatment episodes, and were mostly treated with antihistamines and/or hydrocortisone. No clear predictor of clinical response to porcine factor VIII concentrate was identified, including pretreatment human and porcine inhibitor levels, percentage of cross-reactivity between the human and porcine antibodies, and the presence of measurable levels of factor VIII after the porcine factor concentrate was given. Anamnesis to porcine factor VIII did occur in some instances. Porcine factor VIII is a valuable modality in the treatment of serious hemorrhages in patients with inhibitors to factor VIII. Its use should be considered early in the course of severe hemorrhage in these patients.

Factor VIII:C concentrate purified from plasma using monoclonal antibodies: human studies.

Conventional clotting factor concentrates have, until recently, been "of intermediate purity," containing less than 1% of the coagulation factor, and greater than 99% extraneous plasma proteins such as fibrinogen, fibronectin, gamma globulins, and traces of many others. We report here the results of a new factor VIII concentrate that is purified from human plasma using a mouse monoclonal antibody to factor VIII:vWF in an affinity chromatography system. The resultant concentrate has an activity of between 3,000 and 5,000 U/mg protein before albumin is added as a stabilizer. Seven patients with severe hemophilia A and no inhibitor who were positive for antibody to human immunodeficiency virus (HIV) have been treated solely with this concentrate for over 24 months. Factor usage in these patients has ranged from 611 U/kg/yr to 2,022 U/kg/yr. These patients have infused approximately once per week on the average, most often for joint hemorrhages. The efficacy of the concentrate is excellent. No allergic reactions have occurred and no factor VIII antibodies have developed. In these seven patients mean CD4 counts stabilized (856 +/- 619 at screen v 778 +/- 686 at 24 months) and there was reversal of skin test anergy. In a comparison group on conventional intermediate purity concentrate chosen retrospectively decreases in mean CD4 cell counts similarly did not occur. However, the number of the comparison patients who were anergic increased over the course of the study. These observations indicate the possibility that more highly purified concentrates may stabilize immune function in HIV seropositive patients.

Human immunodeficiency virus isolation studies and antibody testing. Household contacts and sexual partners of persons with hemophilia.

Virus isolation studies and human immunodeficiency virus (HIV) antibody testing were performed on 87 household contacts of 68 HIV antibody-positive hemophilic patients to determine the extent that HIV could be transmitted through heterosexual or through nonsexual, but intimate contact. Human immunodeficiency virus seropositivity was established for the 68 hemophiliacs by immunofluorescence method or enzyme-linked immunosorbent assay and confirmed by Western blot testing (for 66 patients). Fifty-one nonsexual contacts and 36 sexual partners of these hemophiliacs were tested for HIV antibody by immunofluorescence or enzyme-linked immunosorbent assay and Western blot. All sexual partners and all nonsexual household contacts were HIV antibody-negative, including six partners and nine parents of hemophiliacs from whom the virus had been isolated and seven parents and six partners of patients with AIDS. This study further demonstrates lack of transmission of HIV in intimate, but nonsexual settings, and suggests that heterosexual transmission, although well known to occur, may be relatively uncommon in hemophilic couples when the male and female partner have no other risk factors. It is hoped that intensive education and counseling programs will reduce exposure and maintain a low risk of heterosexual transmission.

Isolation of human immunodeficiency virus from hemophiliacs: correlation with clinical symptoms and immunologic abnormalities.

As part of a prospective study of human immunodeficiency virus (HIV) infection in hemophilia, peripheral blood mononuclear cells (PBMs) from 72 individuals without acquired immune deficiency syndrome (AIDS) or AIDS-related complex (ARC) were cultured for virus. HIV was isolated from PBMs from 16 (24%) of 66 patients with hemophilia who were seropositive for HIV and from none of six seronegative patients. Cells from five of six patients from which HIV was isolated were again successfully cultured for virus 3 to 12 months later. HIV core P24 antigen was detected in serum from seven of 15 patients with HIV-positive cells and from eight of 50 with HIV-negative cells. Patients with hemophilia with isolation-positive cells had significantly fewer T helper cells and significantly lower T helper/T suppressor ratios, pokeweed mitogen responsiveness, and total platelet counts than did those whose cells did not yield HIV on cultivation. HIV neutralizing antibody titers did not differ between hemophiliacs with or without HIV-positive PBMs. Three of the 16 patients with virus-positive cells developed AIDS, and two ARC, within 18 months of the study, compared with three of 50 seropositive hemophiliacs whose cells did not yield virus, who developed ARC during the same period. The significant decrease in the number of T helper cells, decreased platelet counts, and higher rate of progression to AIDS in the group with HIV isolation may reflect a heavier virus load, indicating that the ability to culture HIV may be an early marker of more significant disease.

Delayed cutaneous hypersensitivity reactions in hemophiliac subjects treated with factor concentrate.

Cutaneous delayed-type hypersensitivity was measured using the Multitest CMI in a group of 97 patients with hemophilia who were enrolled in the New England Area Comprehensive Clinic. The Multitest CMI is a multipuncture system that dispenses seven test antigens including tetanus, diphtheria, Streptococcus, Proteus, tuberculin, Candida, and Trichophyton, and a glycerine-saline control solution. A reaction was considered positive if there was induration of at least 2 mm. If the results of one or more skin tests were positive, the patient was considered to have a positive reaction. Of the 83 patients with severe or moderate hemophilia A, 51 percent had negative reactions. No study control subject and only one patient with hemophilia B had a negative reaction. The 42 patients with hemophilia A who showed no reaction used a significantly greater amount of factor VIII concentrate than did those with hemophilia A who responded positively (1,960 units/kg per year versus 1,360 units/kg per year; p less than 0.025) and included a higher percent of patients who had seropositive results for human T lymphotropic virus type III (HTLV-III) antibody (89 percent versus 69 percent, p less than 0.025).

Hemophiliac immunodeficiency: influence of exposure to factor VIII concentrate, LAV/HTLV-III, and herpesviruses.

The relationship between hemophiliac immunodeficiency and exposures to factor VIII concentrate, LAV/HTLV-III retrovirus, and infection with Epstein-Barr virus and cytomegalovirus was examined. Exposure to factor VIII concentrate was significantly correlated with decreased percentages of T helper/inducer cells, decreased T helper/suppressor cell ratios, and decreased proliferative responses to plant mitogens. LAV/HTLV-III seropositivity was the primary predictor of increased percentages of HLA-DR-bearing mononuclear cells and decreased proliferative responses to pokeweed mitogen. Epstein-Barr virus and cytomegalovirus infections acted in a synergistic manner with LAV/HTLV-III to produce immunoregulatory defects. Increased percentages of T suppressor cells and decreased delayed cutaneous hypersensitivity skin test responses were observed in LAV/HTLV-III seropositive hemophiliacs infected with Epstein-Barr or cytomegalovirus. We conclude that hemophiliacs receiving commercial factor VIII concentrate experience several stepwise incremental insults to the immune system: alloantigens in factor VIII concentrate, LAV/HTLV-III infections, and herpesvirus infections.

A long-term study of hemophilic arthropathy of the knee joint on a program of Factor VIII replacement given at time of each hemarthrosis.

Because there is little available data to demonstrate whether demand therapy is adequate to prevent progression of hemophilic arthropathy, a cohort of 64 patients with severe Hemophilia A (Factor VIII level less than 1%) and no inhibitor were studied with respect to the progression of knee arthropathy over a period of 6 years. Both degree of disease in flexion and extension and progression of disease were rated on an arbitrary scale. At the outset of the study, the majority of knees were either not restricted or mildly restricted as to motion. Of those knees that were not restricted at the outset, 96% remained not restricted. Of the knees that were mildly restricted, only 58% remained stable or improved over the 6 years, and of the knees that were moderately to severely restricted, 75% improved or remained stable. It thus appears that a demand therapy program can maintain normal range of motion in a knee joint. However, if the patient's joint has progressed to mild disease, the ability to maintain or improve the joint with demand therapy appears to be decreased.