Immune and serologic profiles of HIV-infected and noninfected hemophilic children and adolescents

Objectives: To assess relationships among the effects of HIV on hemophilic children and adolescents' immunologic parameters and vaccine-related serology. Methods: We analyzed data from extensive baseline immunologic evaluations of 207 HIV antibody-positive (HIV+) and 126 HIV antibody-negative (HIV?) hemophilic children and adolescents. Results: HIV+ and HIV- participants differed significantly in T-lymphocyte subpopulation numbers, immunoglobulin levels, and seroprevalence rates for diphtheria toxoid, measles, and mumps antigens. IgG levels, IgM levels, and serologic titers to vaccine antigens showed little correlation with T-cell parameters. Proportionately more HIV+ participants were nonreactive to each and all of a panel of 7 skin test antigens (71 % vs 28% anerglc, RR 2.6). The odds of anergy increased 1.6 times for every decline of 200 CD4 ± cells/μTl. Conclusions: HIV had significant, largely independent T- and B-lymphocyte effects on this pediatric cohort. © 1994 Wiley-Liss, Inc.     

Human immunodeficiency virus infection due to clotting factor concentrates: results of the Seroconversion Surveillance Project

From 1987 to the present, the Seroconversion Surveillance Project has provided the means by which to monitor the risk of transmission of human immunodeficiency virus (HIV) by clotting factor concentrates. One hundred thirty-one hemophilia treatment centers in the United States are contacted regularly, and data on HIV testing of patients are collected. To date, 4366 (46.0%) of 9496 patients have been reported to be seropositive, and 37 new seroconversions have been identified. Nine of these have met the Centers for Disease Control criteria for seroconversion while the patient was taking factor concentrate. None of the nine seroconversions were due to concentrates that had been treated to inactivate viruses and made from plasma that had been tested for HIV antibody. These results indicate that there is a high prevalence of seropositivity in affected patient groups, but that the risk of HIV infection from currently available clotting factor concentrates is extremely low.     

Antibody to human immunodeficiency virus in factor-deficient plasma. Effect of heat treatment on lyophilized plasma

The prevalence of antibody to human immunodeficiency virus (HIV) was determined in various commercial substrate plasmas used in clotting factor assays, and viral isolation was attempted from both seropositive and seronegative samples. Antibody to HIV was detected in 13 of 13 plasma substrates used for Factor VIII assays and in 2 of 3 plasma substrates used for Factor IX assays. Antibodies were not detected in any of the other factor-specific substrates. Virus could not be isolated from any of the seropositive samples after 28 days in culture. Heat treatment of the samples under conditions known to inactivate HIV in plasma products indicated that heating the lyophilized substrate plasmas at 60 degrees C for up to eight hours had little effect on factor substrates and factor assays. Progressive loss of Factor V in the deficient plasmas was the most serious effect produced by heat treatment.     

Hemophilia-associated AIDS in the United States, 1981 to September 1987.

Between January 1, 1981 and September 4, 1987, 407 cases of hemophilia-associated acquired immunodeficiency syndrome (AIDS) had been reported to the Centers for Disease Control. The number of cases diagnosed each year nearly doubled, except in 1986, when cases increased only 50 per cent. Demographic characteristics of the patients did not change over time. The majority (74 per cent) had severe hemophilia and 97 per cent received commercially produced concentrated clotting factors. The cumulative incidence of AIDS between 1981 and September 1987 for persons with severe hemophilia A was substantially greater than that for persons with severe hemophilia B (4.2 cases vs 1.9 cases per 100 persons).     

Human T-cell leukemia virus in lymphocytes of two hemophiliacs with the acquired immunodeficiency syndrome

Fresh and cultured peripheral blood cells from two patients with hemophilia A and the acquired immunodeficiency syndrome were examined for markers of infection with human T-cell leukemia virus (HTLV) type 1. Neither patient had antibody to membrane antigens of HTLV-infected cells at the time of culture. Electron microscopy of peripheral blood cells from Patient 1 and cultured cells from Patient 2 showed type C retrovirus-like particles. Examination of peripheral blood lymphocytes showed other smaller virus-like particles in circulating mononuclear cells from both patients. Indirect immunofluorescence of peripheral mononuclear cells from both patients and of cultured cells from Patient 2 showed staining with antibodies to purified HTLV and to HTLV core proteins p24 and p19.     

Acquired immunodeficiency syndrome (AIDS) in hemophilia

Between early 1980 and early 1984, more than 4000 cases of AIDS have occurred in the United States. Since January 1982, 33 cases have occurred in patients with hemophilia. The epidemiologic and clinical features of the cases are presented. Etiologic considerations and implications for blood products are discussed.     

Medical, reproductive and psychosocial experiences of women diagnosed with von Willebrand''s disease receiving care in haemophilia treatment centres: a case–control study

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.     

Measurement of von Willebrand factor activity: relative effects of ABO blood type and race

Summary.  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.     

Hepatitis A virus infections associated with clotting factor concentrate in the United States

BACKGROUND: Two cases of hepatitis A among persons exposed to the same lot of solvent/detergent-treated antihemophilic factor VIII concentrate were reported to a surveillance system. An investigation was conducted to find additional cases and determine the source of infection. STUDY DESIGN AND METHODS: A seroprevalence study was conducted among persons with exposure to the suspect lot for serologic evidence of recent infection with hepatitis A virus (HAV). RESULTS: Six cases of recent HAV infection were discovered: four of the patients had been infused with material from the suspect lot of factor VIII, and two had received infusions of factor IX concentrate made from plasma pools common to the suspect factor VIII lot. HAV was identified in one of the plasma pools, in the factor VIII product, and in serum or stool from two factor VIII recipients and one factor IX recipient. The genetics sequence of the virus in the plasma pool, the factor VIII lot, and the factor VIII recipients were identical, while that of the virus in the factor IX recipient differed by a single base. CONCLUSION: These data document the transmission of HAV by a factor VIII concentrate and implicate factor IX products manufactured from a common source-plasma pool.