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.
-
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
MHCS-II
Total Subjects
Unknown
896
5
901
< 1
11
.
11
1-18
307
117
424
18-29
392
698
1,090
30-39
273
505
778
40-49
104
435
539
50-59
47
240
287
60-69
27
119
146
70-79
4
35
39
80-89
.
11
11
Last Modified: July 3, 2024, 8:32 a.m. -
Sex
MHCS-I
MHCS-II
Total Subjects
Unknown
21
5
26
Male
1,979
2,032
4,011
Female
61
128
189
Last Modified: July 3, 2024, 8:32 a.m. -
Race
MHCS-I
MHCS-II
Total Subjects
Unknown
21
5
26
White
1,672
1,768
3,440
Black
225
149
374
Other
143
243
386
Last Modified: July 3, 2024, 8:32 a.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
-
Material Types
-
General Freeze/Thaw Status
-
Visits (Vials)
07/03/2024
Serum
Plasma
DNA
PERIPHERAL BL MONO CELLS
Total Vials
Subjects with 1 visit
1,164
8,113
7,170
3,912
20,359
Subjects with 2 visits
1,829
16,689
2,603
9,192
30,313
Subjects with 3 visits
1,740
27,163
317
15,342
44,562
Subjects with 4 visits
1,701
24,543
39
12,618
38,901
Subjects with 5-10 visits
5,625
55,190
21
20,575
81,411
Subjects with 11+ visits
13,632
69,386
.
22,483
105,501
Subjects with no visit date
.
.
3
.
3
Last Modified: July 3, 2024, 8:32 a.m. -
Visits (Subjects)
07/03/2024
Serum
Total number of subjects
Average volume (mL) per subject
Subjects with 1 visit
299
1.45
Subjects with 2 visits
241
2.97
Subjects with 3 visits
168
4.35
Subjects with 4 visits
126
5.56
Subjects with 5-10 visits
263
8.28
Subjects with 11+ visits
211
23.89
Plasma
Total number of subjects
Average volume (mL) per subject
Subjects with 1 visit
722
5.18
Subjects with 2 visits
751
10.50
Subjects with 3 visits
798
16.25
Subjects with 4 visits
535
22.36
Subjects with 5-10 visits
713
39.85
Subjects with 11+ visits
396
97.82
DNA
Total number of subjects
Average mass (ug) per subject
Subjects with no visit date
1
3.00
Subjects with 1 visit
1,788
4.01
Subjects with 2 visits
420
6.20
Subjects with 3 visits
45
7.04
Subjects with 4 visits
4
9.75
Subjects with 5-10 visits
1
21.00
PERIPHERAL BL MONO CELLS
Total number of subjects
Average volume (mL) per subject
Subjects with 1 visit
709
5.52
Subjects with 2 visits
792
11.61
Subjects with 3 visits
814
18.85
Subjects with 4 visits
525
24.03
Subjects with 5-10 visits
646
31.85
Subjects with 11+ visits
298
75.45
Last Modified: July 3, 2024, 8:34 a.m.