The consistent improvements in hemophilia care seen in the years 1960 to 1980 halted when human immunodeficiency virus (HIV) appeared in the blood supply. In the early 1980s, before HIV virulence was fully understood, a complacent blood therapy industry and its regulators waffled on an appropriate response. As a result, the period between the appearance of HIV and its effective elimination from the blood supply was lengthy and many recipients of blood therapies became infected, with devastating impact on their quality of life, quality of care, and longevity. As the decade wore on, even as they began to better understand the threat, industry and public health officials continued to stall, in part because development of interventions was costly and cumbersome. In order to protect the safety of the blood supply and blood-derived therapies, it must be recognized that new pathogens will continue to emerge. Agencies' and companies' decision-making processes in this regard must therefore be proactive rather than reactive, and should preferably implement a formalized risk-management approach. The ongoing safety of blood therapies and the blood supply will also depend on continued vigilance and research. Finally, the hemophilia community must be allowed to play an active and educated role in their own care.

After the dissolution of Soviet Union in 1991, haemophilia care in the Republic of Georgia was negatively affected because of the expense of treatment products, lack of clinical and diagnostic facilities, and the need for trained personnel throughout the country. In 2001, the Georgian Government, working through the Ministry of Health, in collaboration with Georgian Association of Haemophilia and Donors, the Institute of Haematology and Transfusion, and the World Federation of Haemophilia, initiated a National Haemophilia Programme. As part of this programme the first Georgian Haemophilia Treatment Centre (HTC) was established. In this paper, we will describe (i) our outreach efforts to identify patients with haemophilia (PWH), (ii) the diagnostic and clinical services provided to patients by the HTC, and (iii) the results of a patient survey designed to assess patient satisfaction with the care provided. Total of 216 PWH were diagnosed, mean age was 25 years (range 4 months to 75 years); 43% had severe, 33% had moderate and 24% had mild haemophilia A or B. Overall, 183 (85%) had haemophilia A and 33 (15%) had haemophilia B, giving a ratio of 5.6. During the 2-year period, 77% of the expected number of PWH was identified by our outreach programme. Vast majority had comprehensive evaluation including joint assessment and over 60% were tested for blood-borne infections within a year and half period. Our findings showed that haemophilia care was considerably improved since the beginning of the National Haemophilia Programme and the survey of PWH showed a high degree of satisfaction with services provided in the HTC. In conclusion, close collaboration of the government, non-government entities and medical professionals in a Georgian national haemophilia care model; resulted in the successful delivery of the much needed services and care to the people living in Georgia with haemophilia.

Objective: To assess the management of women with von Willebrand disease( vWD) in an Heamophilia Treatment Center (HTC) setting. Methods: A total of 75 women with vWd who were registered in HTCs in the United States participated in this study. A telephone interview elicited information about symptoms pertaining to bleeding disorders, diagnostic issues, referral patterns, treatment modalities before and after the enrollment in the HTC, HTC services provided, and satisfaction with care in the HTC. Results: Menorrhagia was the most commonly reported symptom (84%). The average time from the first symptom until clinician recognition was 16 years (range 0-39). In HTC, DDAVP was the most commonly used drug (31%). Of the 75 women, 71 reported a strong positive opinion and satisfaction about their care in the HTCs. Discussion: Women with VWD were typically diagnosed with the condition well into adulthood, in spite of the fact that majority of them experienced several bleeding symptoms beginning in early childhood. In general an HTC setting is appropriate for management of women with bleeding disorders. Diagnosis, treatment and education provided in the HTCs were viewed positively by those surveyed.

Objective: To assess the medical, gynaecological and reproductive experiences of women with von Willebrand's disease (VWD) and to evaluate the impact of VWD on mental health and life activities.Methods: A total of 102 women with VWD who were registered in haemophilia treatment Centres (HTCs) in the United States and 88 controls were interviewed regarding medical, gynaecological and reproductive history, life activities and symptoms of depression. Symptoms of depression were measured using the Center for Epidemiological Studies Depression Scale (CES-D).Results: Excessive bleeding symptoms were reported in 74% of VWD cases compared with 6% of controls. Women with VWD had a higher prevalence of menorrhagia, excessive postpartum bleeding, other gynaecological conditions, arthritis and migraine headaches than did controls. More VWD cases than controls reported that menstruation had a negative impact on overall life activities. No difference in the prevalence of depression was found between cases and controls.Discussion: Women with VWD experience menorrhagia and other gynaecological conditions at a higher frequency than women without bleeding disorders. Menstruation in women with VWD has a negative impact on life activities. The prevalence of depression was not elevated in this group of women whose VWD is being managed in an HTC.

Legg-Perthes disease is a pediatric hip disorder characterized by avascular necrosis of the femoral head. The etiology of Legg-Perthes disease may involve repeated interruptions of the blood supply to the proximal femur. Thus, the role of thrombosis in Legg-Perthes disease is of interest. The focus of this analysis is an evaluation of the relationship between Legg-Perthes disease and the beta fibrinogen gene G-455-A polymorphism in 55 cases of Legg-Perthes disease and 56 age, race, and gender-matched healthy controls. Parents of subjects completed a questionnaire about their child's lifestyle and medical history. Blood was obtained for plasma and DNA analysis. Study subjects were predominantly white (93%), male (77%) and under age 16 (70%). Cases were more likely to be exposed to passive smoke than were controls (odds ratio 5.6, 95% confidence interval 2.0-12.0). Assuming a dominant genetic model, individuals who possessed either the G/A or A/A genotype were over three times more likely to have Legg-Perthes disease compared to those without the polymorphism (odds ratio 3.4, 95% confidence interval 1.5-7.8). Separate analyzes by smoke exposure revealed that the excess risk of the G-455-A polymorphism occurred in those exposed (odds ratio 7.0) as opposed to those unexposed to passive smoke (odds ratio 1.9). Although this difference in the odds ratios is not statistically significant (P=0.2), it suggests a possible interactive effect of cigarette smoke and the b fibrinogen gene G-455-A polymorphism in the risk of developing Legg-Perthes disease.

Tests based on three different principles are reported to measure the activity of von Willebrand factor (VWF): ristocetin cofactor (VWF:RCo), collagen binding (VWF:CB), and the so-called "activity ELISA" (VWF:MoAb). We measured these and other diagnostic parameters in a population of 123 randomly selected female study controls, age 18-45 years. Type O subjects had significantly lower levels than non-O subjects in each test. Race differences were seen in all tests except VWF:RCo, with Caucasians having significantly lower levels than African-Americans. ABO differences accounted for 19% of the total variance in VWF:Ag (P < 0.0001) and race for 7% (P < 0.0001), for a total of 26%. Both effects were mediated through VWF:Ag and were independent. VWF:Ag level was the primary determinant of VWF function, accounting for approximately 60% of the variance in VWF:RCo and VWF:CB and 54% of the variance in factor VIII. The ratio VWF:RCo/VWF:Ag differed significantly by race within blood group. The median ratios were 0.97 for type O Caucasians vs. 0.79 for type O African-Americans and 0.94 for non-O Caucasians vs. 0.76 for non-O African-Americans. The ratio VWF:CB/VWF:Ag did not vary. This suggests racial differences in the interaction of VWF with GP1b but not with subendothelium. Alternatively, VWF:RCo may be regulated to maintain a relatively constant plasma level in the presence of excessive VWF:Ag. This heterogeneity within the normal population is partially responsible for the difficulty in defining diagnostic limits for von Willebrand disease.

Menorrhagia is a common clinical problem and is unexplained in more than 50% of women. Although studies suggest that von Willebrand's Disease (VWD) is found in a substantial number of women with unexplained menorrhagia, the prevalence of platelet defects in women with menorrhagia is unknown. To determine the prevalence of platelet and other hemostatic defects, we evaluated women ages 17-55 diagnosed with unexplained menorrhagia. Seventy-four women (52 white, 16 black, six other) were studied. Bleeding time was prolonged in 23 women (31.5%). Maximal percent platelet aggregation was decreased with one or more agonists in 35 (47.3%) women. The most commonly found platelet function defects were reduced aggregation responses to ristocetin in 22 women and to epinephrine in 16 women. Sixteen of 22 women with reduced ristocetin aggregation had von Willebrand ristocetin cofactor (VWF:RCo) and von Willebrand factor antigen (VWF:Ag) > 60%. Platelet ATP release was decreased with one or more agonists in 43 (58.1%) women. Of the black women studied, 11/16 (69%) had abnormal platelet aggregation studies compared with 20/52 white women (39%) (P = 0.06). Black women with menorrhagia had a higher prevalence of decreased platelet aggregation in response to ristocetin and epinephrine than did white women (P = 0.0075, P = 0.02). Ten women (13.5%) had VWF:RCo and/or VWF:Ag < 60%. Using race and blood group specific ranges, 5 (6.8%) women had decreased VWF:RCo, VWF:Ag and/or collagen binding (VWF:CB). Mild factor XI deficiency was found in two women and one woman with mild factor V deficiency and one hemophilia A carrier were identified. We conclude that the prevalence of platelet function defects and other inherited bleeding disorders is substantial in a multiracial US population of women with unexplained menorrhagia.

Objective: To estimate the prevalence of von Willebrand disease and other bleeding disorders in women with and without diagnosed menorrhagia.Methods: Women with menorrhagia were identified among members of a health maintenance organization in the southeastern United States through a computer search for appropriate international Classification of Diseases, 9th Revision codes. A random sample of members with no such code was selected as controls. The study included 121 women with menorrhagia and 123 controls. Subjects were interviewed in person, and blood was drawn for coagulation testing. Laboratory results for menorrhagia patients were compared with those in controls using race and blood type specific ranges developed from the control group. A test was considered abnormal if it exceeded two standard deviations below the control mean.Results: Bleeding disorders (von Willebrand disease, factor deficiency, or a platelet abnormality) were diagnosed in 10.7% of menorrhagia patients and 3.2% of controls (P = .02). von Willebrand disease was present in eight menorrhagia patients (6.6%) and in one control (0.8%) (P = .02); separate analyses by race revealed a von Willebrand disease prevalence of 15.9% among white and 1.4% among black menorrhagia patients (P = .01). Women with bleeding disorders did not differ significantly from controls in other symptoms of bleeding.Conclusion: The prevalence of inherited bleeding disorders among white women with menorrhagia was substantial, consistent with European data published recently. For unknown reasons, the prevalence of von Willebrand disease was lower among black women. These findings indicate the importance of considering inherited bleeding disorders as a cause of menorrhagia. (C) 2001 by The American College of Obstetricians and Gynecologists.

HaemophiliaVolume 6, Issue s1 p. 94-99 Creutzfeldt-Jakob Disease and haemophilia: assessment of risk † Evatt, Evatt Centers for Disease Control and Prevention, Atlanta, U.S.A.Search for more papers by this author Evatt, Evatt Centers for Disease Control and Prevention, Atlanta, U.S.A.Search for more papers by this author First published: 04 January 2002 https://doi.org/10.1046/j.1365-2516.2000.00052.xCitations: 7 c/o World Federation of Hemophilia, 1425 René Lévesque Boulevard West, Suite 1010, Montréal, Québec H3G 1T7, Canada. Tel: +1 514 875 7944; Fax: +1 514 875 8916. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume6, Issues1July 2000Pages 94-99 RelatedInformation

We evaluated the relation between venous thrombosis and plasma fibrinogen levels, the HaeIII and BcI polymorphisms of the beta fibrinogen gene, and the MspI polymorphisms of the factor VII gene in a case-control study of African-Americans. The study included 91 venous thrombosis cases and 185 control subjects obtained from a hospital in Atlanta, Georgia. High plasma fibrinogen was associated with increased risk of venous thrombosis, but the finding was not statistically significant. There was little association between the HaeIII polymorphisms and the BclI polymorphisms and the risk of venous thrombosis. The prevalence of the M2/M2 genotype of the factor VII gene was higher among cases than controls, but the difference was not statistically significant. The prevalence of the HaeIII H2 allele and the BclI B2 allele of the beta fibrinogen gene, both of which have been associated with slightly higher levels of plasma fibrinogen in most studies, is considerably lower among African-Americans in this study than it is among Whites in the United States and among Northern Europeans. The study is limited by its small size. However, despite this limitation, it supports the belief that increased plasma fibrinogen levels are associated with increased venous thrombosis risk. The study also indicated that the HaeIII and the BclI polymorphisms of the beta fibrinogen gene and the MspI polymorphisms of the factor VII gene are not strong determinants of venous thrombosis.

Most of the world's haemophilia population lives in countries with few medical or financial resources. As such, they cannot easily obtain viral-inactivated clotting product. Many patients are treated with cryoprecipitate made from locally supplied blood. The reasoning for using cryoprecipitate, instead of viral-inactivated products, is based on an unspoken belief that because blood banks can provide reasonably safe products by using modern testing procedures, transmission of HIV and other blood-borne viruses is rare. However, the risk of acquiring a blood-borne infection increases with every exposure, and haemophilia patients treated with cryoprecipitate or fresh-frozen plasma are exposed to hundreds or thousands of donors during their lifetime. The risk that a person infected with HIV will donate blood during the 'window period' is directly related to the incidence of HIV in the country where the donation occurs. To demonstrate the extent of this problem, we devised a model for estimating the risk that a person with haemophilia will encounter HIV-contaminated cryoprecipitate based on the years of treatment and the underlying incidence rate of HIV among blood donors. We applied the model to two countries with different incidence rates of HIV: Venezuela and the United States. We found that a person with haemophilia who receives monthly infusions of cryoprecipitate prepared from plasma of 15 donors over a lifetime of treatment (60 years) is at significant risk of being exposed to HIV. In the United States there is a 2% risk of being exposed to HIV-contaminated blood product, and in Venezuela, the percentage of risk is 40%. Given this degree of risk, medical care providers should carefully evaluate the use of cryoprecipitate except in emergencies or when no viral-inactivated products are available.