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Home > Studies > MHCS > Catalog

Multicenter Hemophilia Cohort Studies (MHCS) - Catalog

Basic Study Information

Name

Multicenter Hemophilia Cohort Studies (MHCS)

Accession Number

HLB00941221a

Acronym

MHCS

Related studies

BSI Study IDs

HEB

HEM

Is public use dataset

False

Keywords

Has Study Datasets

True

Has Specimens

True

Specimen ID Type

Coded

Study Website

The Framingham Heart Study Group requires that the requestor must obtain full or expedited IRB/Ethics Committee review and approval to obtain these data. Waivers or a determination that the research is exempt from ethical regulations do not suffice.

False

Clinical Trial URLs
https://clinicaltrials.gov/ct2/show/NCT00341705
Study type

Epidemiology Study

Collection Type

Open BioLINCC Study

Cohort type

Both

Interventions

Study Open Date (Data)

2012-09-04

Study Open Date (Specimens)

2010-09-24

Date materials available

2010-06-08

Last updated

2012-09-01

Study period

MHCS-I: 1982-1996 ; MHCS-II: 2001-2005

Study Contacts
NHLBI Division

DBDR

Classification

Blood Disease

HIV study classification

HIV

COVID study classification

non-COVID

Pre-Website # of Specimens Shipped

22

# of Returned Specimens

0

Primary Publication URLs
N/A

Study Consent

Commercial use data restrictions

No

Data restrictions based on area of research

No

Commercial use specimen restrictions

No

Non-genetic use specimen restrictions based on area of use

Yes

Genetic use of specimens allowed?

Yes

Genetic use area of research restrictions

Yes

Specific Consent Restrictions

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.

Additional Study Information

Conditions

Hepatocellular Carcinoma
Liver Failure
Non-Hodgkin Lymphoma

Objectives

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.

Background

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.

Subjects

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".

Design

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.

Conclusions

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.

Disease classification

Publications

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

Mat types

DNA
Peripheral Blood Mononuclear Cells
Plasma
Red Blood Cells
Serum

Study Population

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: April 28, 2022, 8:12 a.m.
  • Age

    MHCS-I:

     

    Frequency

    Percent

    Cumulative
    Frequency

    Cumulative
    Percent

    Unknown

    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
    Frequency

    Cumulative
    Percent

    Unknown

    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: April 28, 2022, 8:12 a.m.
  • Sex

    MHCS-I:

     

    Frequency

    Percent

    Cumulative
    Frequency

    Cumulative
    Percent

    Unknown

    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
    Frequency

    Cumulative
    Percent

    Unknown

    5

    0.19

    5

    0.19

    Male

    2431

    94.59

    2436

    94.79

    Female

    134

    5.21

    2570

    100.00

     

    Last Modified: April 28, 2022, 8:12 a.m.
  • Race

    MHCS-I:

     

    Frequency

    Percent

    Cumulative
    Frequency

    Cumulative
    Percent

    Unknown

    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
    Frequency

    Cumulative
    Percent

    Unknown

    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: April 28, 2022, 8:12 a.m.

Available Biospecimens

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)

    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: April 28, 2022, 8:12 a.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: April 28, 2022, 8:12 a.m.
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