Multicenter Hemophilia Cohort Studies (MHCS) - Catalog
Multicenter Hemophilia Cohort Studies (MHCS)
HLB00941221a
MHCS
HEB
HEM
False
True
True
Coded
False
Epidemiology Study
Open BioLINCC Study
Both
2012-09-04
2010-09-24
2010-06-08
2012-09-01
MHCS-I: 1982-1996 ; MHCS-II: 2001-2005
DBDR
Blood Disease
HIV
non-COVID
22
0
No
No
No
Yes
Yes
Yes
Consent for MHCS I specimens restricts their use to research related to hemophilia or its complications (which includes HIV, AIDS, hepatitis and other viruses). Consent for MHCS II specimens restricts their use to research related to HIV, HCV, other viruses, human genes (DNA), and future developments that are relevant to these viruses, hemophilia and their complications.
Hepatocellular Carcinoma
Liver Failure
Non-Hodgkin Lymphoma
The First Multicenter Hemophilia Cohort Study (MHCS-I) evaluated and prospectively followed patients with hemophilia or a related coagulation disorder. Initiated in 1982, this study particularly sought to understand the cause and natural history of HIV infection and AIDS in this population which was at high risk for development of AIDS.
The Second Multicenter Hemophilia Cohort Study (MHCS-II) evaluated and prospectively followed a cohort of subjects with hemophilia who were exposed to hepatitis C virus (HCV). The primary objectives were to quantify the rates of liver decompensation, hepatocellular carcinoma, and non-Hodgkin lymphoma and to evaluate candidate clinical, genetic, virologic, serologic and immunologic markers that are likely to be on the causal pathway for these conditions, identify predictive clinical and laboratory markers and follow the markers over time, identify host genes that confer susceptibility or resistance to HCV and HIV infections or to the diseases that result from these infections and to identify response and complication rates of various anti-HCV and anti-HIV regimens in the setting of comprehensive clinical care of persons with hemophilia.
Treatment of hemophilia patients with contaminated plasma products before 1990 resulted in extraordinary prevalence rates of human immunodeficiency virus (HIV) and hepatitis B and C viruses (HBV, HCV). The first cases of acquired immunodeficiency syndrome (AIDS) were reported in the United States in 1981 and the first cases of AIDS in hemophilia patients were reported one year later. In contrast to HIV-1, HBV, HCV were present in the human population and HBV and HCV were almost certainly was always a contaminant of blood and plasma donated for transfusion prior to the development of diagnostic tests to screen blood donors.
Adults and children who had a congenital coagulation disorder [hemophilia A or B (congenital factor VIII or IX deficiency)] von Willebrand's disease, or other were enrolled from 8 collaborating hemophilia centers in the US between 1982 and 1985. Four additional centers from the US and 4 centers from Europe joined the study between 1987 and 1990.
In MHCS-II, 52 collaborating hemophilia centers in North and South America and Europe, enrolled patients who had a congenital coagulation disorder [hemophilia A or B (congenital factor VIII or IX deficiency), von Willebrand's disease, or other], who had reached 13 years of age, and who had serological or molecular evidence of HCV or HIV-1 infection. The majority of subjects consisted of a "HCV cohort" of whom a portion was co-infected with HIV, the "HIV cohort".
In MHCS-I, subjects were evaluated semiannually with a standardized physical examination, abstraction of medical records, and phlebotomy.
In MHCS-II, The natural time scale was used, beginning with the estimated date of HCV or HIV infection to an event of interest, death, or censoring. Time initiated on the estimated date of HCV infection (HCV cohort) or HIV infection (HIV cohort) but follow-up was defined as the date of the first blood sample collected for the MHCS-I or -II. The main outcomes were liver decompensation, hepatocellular carcinoma and non-Hodgkin lymphoma. Measures included HCV viral load, anti-HCV levels and other markers of the primary outcomes such as serum cholesterol and inflammatory cytokine levels; host genetic polymorphism.
Nearly one-third of the MHCS-II participants were infected with HIV-1, many of whom were infected in childhood and all of whom have survived with HIV-1 for more than 15 years. As survivors, relatively few of them had an AIDS-defining opportunistic infection or malignancy (17%) or laboratory-defined AIDS. In contrast to use of HAART for HIV-1 infection, only a minority of MHCS-II participants had been treated for their HCV infection. In the MHCS-II cohort of HCV-seropositive people with hemophilia and related coagulation disorders, the prevalence rates of ascites, hepatomegaly, splenomegaly and persistent jaundice were 2- to 3-fold higher with HIV-1, when adjusted for age and most could not be ascribed to HAART or other anti-HIV-1 regimens.
In the MHCS-II, 74% of the HIV-1-positive and 51% of the HIV-1-negative participants had evidence of current or previous HBV infection. In MHCS-I, the risk of decompensated end stage liver disease was increased 8.1-fold for carriers of hepatitis B surface antigen (HBsAg) and 3.4-fold for the much larger group of hemophiliacs who had cleared HBsAg.
Melendez-Morales L, Konkle BA, Preiss L, Zhang M, Mathew P, Eyster ME, Goedert JJ. Chronic hepatitis B and other correlates of spontaneous clearance of hepatitis C virus among HIV-infected people with hemophilia. AIDS. 2007; 21(12):1631-6.
Goedert JJ; Second Multicenter Hemophilia Cohort Study. Prevalence of conditions associated with human immunodeficiency and hepatitis virus infections among persons with haemophilia, 2001-2003. Haemophilia. 2005; 11(5):516-28.
Engels EA, Frisch M, Lubin JH, Gail MH, Biggar RJ, Goedert JJ. Prevalence of hepatitis C virus infection and risk for hepatocellular carcinoma and non-Hodgkin lymphoma in AIDS. J Acquir Immune Defic Syndr. 2002; 31(5):536-41.
Goedert JJ, Eyster ME, Lederman MM, Mandalaki T, De Moerloose P, White GC 2nd, Angiolillo AL, Luban NL, Sherman KE, Manco-Johnson M, Preiss L, Leissinger C, Kessler CM, Cohen AR, DiMichele D, Hilgartner MW, Aledort LM, Kroner BL, Rosenberg PS, Hatzakis A. End-stage liver disease in persons with hemophilia and transfusion-associated infections. Blood. 2002; 100(5):1584-9.
O'Brien TR, Blattner WA, Waters D, Eyster E, Hilgartner MW, Cohen AR, Luban N, Hatzakis A, Aledort LM, Rosenberg PS, Miley WJ, Kroner BL, Goedert JJ. Serum HIV-1 RNA levels and time to development of AIDS in the Multicenter Hemophilia Cohort Study. JAMA. 1996; 276(2):105-10.
Ehmann WC, Eyster ME, Wilson SE, Andes WA, Goedert JJ. Relationship of CD4 lymphocyte counts to survival in a cohort of hemophiliacs infected with HIV. Multicenter Hemophilia Cohort Study. J Acquir Immune Defic Syndr. 1994;7(10):1095-8.
Goedert JJ, Cohen AR, Kessler CM, Eichinger S, Seremetis SV, Rabkin CS, Yellin FJ, Rosenberg PS, Aledort LM. Risks of immunodeficiency, AIDS, and death related to purity of factor VIII concentrate. Multicenter Hemophilia Cohort Study. Lancet. 1994; 344(8925):791-2. Erratum in: Lancet 1994; 344(8931):1238.
Eyster ME, Fried MW, Di Bisceglie AM, Goedert JJ. Increasing hepatitis C virus RNA levels in hemophiliacs: relationship to human immunodeficiency virus infection and liver disease. Multicenter Hemophilia Cohort Study. Blood. 1994; 84(4):1020-3.
Goedert JJ, Kessler CM, Aledort LM, Biggar RJ, Andes WA, White GC 2nd, Drummond JE, Vaidya K, Mann DL, Eyster ME, et al. A prospective study of human immunodeficiency virus type 1 infection and the development of AIDS in subjects with hemophilia. N Engl J Med.1989; 321(17):1141-8.
Lozier JN, Rosenberg PS, Goedert JJ, Menashe I. (2011), A case–control study reveals immunoregulatory gene haplotypes that influence inhibitor risk in severe haemophilia A. Haemophilia, 17: no. doi: 10.1111/j.1365-2516.2010.02473.x
DNA
Peripheral Blood Mononuclear Cells
Plasma
Red Blood Cells
Serum
The study population available in BioLINCC study data may be lower than total study enrollment due to Informed Consent restrictions and other factors.
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Subjects
MHCS-I: 2061
MHCS-II: 2570
*There are 405 subjects enrolled in MHCS-I and MHCS-II
Last Modified: Nov. 17, 2023, 12:44 p.m. -
Age
MHCS-I:
Frequency Percent Cumulative
FrequencyCumulative
PercentUnknown 896 43.47 896 43.47 <1 11 0.53 907 44.01 1-10 134 6.50 1041 50.51 11-20 270 13.10 1311 63.61 21-30 331 16.06 1642 79.67 31-40 249 12.08 1891 91.75 41-50 95 4.61 1986 96.36 51-60 47 2.28 2033 98.64 61-70 25 1.21 2058 99.85 71-80 3 0.15 2061 100.00 MHCS-II:
Frequency Percent Cumulative
FrequencyCumulative
PercentUnknown 5 0.19 5 0.19 11-20 351 13.66 356 13.85 21-30 654 25.45 1010 39.30 31-40 623 24.24 1633 63.54 41-50 500 19.46 2133 83.00 51-60 281 10.93 2414 93.93 61-70 109 4.24 2523 98.17 71-80 39 1.52 2562 99.69 >80 8 0.31 2570 100.00
Last Modified: Nov. 17, 2023, 12:44 p.m. -
Sex
MHCS-I:
Frequency Percent Cumulative
FrequencyCumulative
PercentUnknown 24 1.16 24 1.16 Male 1976 95.88 2000 97.04 Female 61 2.96 2061 100.00 MHCS-II:
Frequency Percent Cumulative
FrequencyCumulative
PercentUnknown 5 0.19 5 0.19 Male 2431 94.59 2436 94.79 Female 134 5.21 2570 100.00
Last Modified: Nov. 17, 2023, 12:44 p.m. -
Race
MHCS-I:
Frequency Percent Cumulative
FrequencyCumulative
PercentUnknown 24 1.16 24 1.16 White 1670 81.03 1694 82.19 Black 225 10.92 1919 93.11 Other 142 6.89 2061 100.00 MHCS-II:
Frequency Percent Cumulative
FrequencyCumulative
PercentUnknown 5 0.19 5 0.19 White 2056 80.00 2061 80.19 Black 214 8.33 2275 88.52 Other 295 11.48 2570 100.00
Last Modified: Nov. 17, 2023, 12:44 p.m.
Please note that biospecimen availability is subject to review by the NHLBI, BioLINCC, and the NHLBI Biorepository. Certain biospecimens may not be made available for your request. Section 3 of the BioLINCC handbook describes the components of the review process
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Material Types
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General Freeze/Thaw Status
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Visits (Vials)
04/28/2022
Serum Plasma Red Blood Cells DNA PBMC Total Subjects with 1 visit 1,198 7,969 1,232 7,222 3,976 21,597 Subjects with 2 visits 1,824 16,874 2,424 2,641 9,306 33,069 Subjects with 3 visits 1,747 26,854 2,241 317 15,426 46,585 Subjects with 4 visits 1,693 25,527 657 27 12,772 40,676 Subjects with 5-10 visits 5,646 55,923 10 39 20,683 82,301 Subjects with 11+ visits 13,638 68,569 0 0 22,392 104,599 Subjects with no visit date 9 109 0 3 8 129
Last Modified: Nov. 17, 2023, 12:44 p.m. -
Visits (Subjects)
04/28/2022
Serum Total number of subjects Average volume (ml) per subject Subjects with 1 visit 309 1.44 Subjects with 2 visits 241 2.95 Subjects with 3 visits 169 4.34 Subjects with 4 visits 125 5.58 Subjects with 5-10 visits 265 8.24 Subjects with 11+ visits 211 23.90 Subjects with no visit date 5 0.84 Plasma Total number of subjects Average volume (ml) per subject Subjects with 1 visit 747 4.97 Subjects with 2 visits 767 10.40 Subjects with 3 visits 789 16.28 Subjects with 4 visits 557 22.27 Subjects with 5-10 visits 726 39.66 Subjects with 11+ visits 396 97.17 Subjects with no visit date 24 2.64 PBMC Total number of subjects Average vials per subject Subjects with 1 visit 724 5.49 Subjects with 2 visits 794 11.72 Subjects with 3 visits 813 18.97 Subjects with 4 visits 526 24.28 Subjects with 5-10 visits 647 31.97 Subjects with 11+ visits 301 74.39 Subjects with no visit date 1 8.00 Red Blood Cells Total number of subjects Average vials per subject Subjects with 1 visit 625 1.97 Subjects with 2 visits 608 3.99 Subjects with 3 visits 374 5.99 Subjects with 4 visits 82 8.01 Subjects with 5-10 visits 1 10.00 DNA Total number of subjects Average mass (µg) per subject Average vials per subject Subjects with 1 visit 1,814 13.37 3.98 Subjects with 2 visits 425 17.59 6.21 Subjects with 3 visits 45 16.14 7.04 Subjects with 4 visits 3 25.18 9.00 Subjects with 5-10 visits 2 11.70 19.50 Subjects with no visit date 1 2.32 3.00
Last Modified: Nov. 17, 2023, 12:44 p.m.