High Prevalence of Serum Cryoglobulins in Multitransfused Hemophilic
Patients With Chronic Hepatitis C
E. Santagostino,
M. Colombo,
D. Cultraro,
M. Muça-Perja,
A. Gringeri, and
P.M. Mannucci
From the Angelo Bianchi Bonomi Hemophilia and Thrombosis Center and
the Department of Internal Medicine, IRCCS Maggiore Hospital and
University of Milan, Milan, Italy.
The prevalence, clinical relevance, and risk factors of serum
cryoglobulins in hemophilic patients with chronic hepatitis C virus
(HCV) infection are unknown. We studied 135 consecutive hemophilic
patients (median age, 31 years; range, 10 to 69 years) with chronic
hepatitis C, exposed to the virus for 10 to 41 years. A total of 67 patients were coinfected with the human immunodeficiency virus (HIV),
and 3 (2%) had signs of cirrhosis. Serum samples were tested for the
presence of cryoglobulins, hepatitis B virus (HBV) markers, including
HBV-DNA by hybridization assay, and antibody to HCV by enzyme
immunoassay (EIA). Serum HCV-RNA was tested by polymerase
chain reaction and typed with a hybridization technique. Samples were
also tested for antitissue antibodies, immunoglobulins, rheumatoid factor, and C3 and C4 proteins
of complement. Forty-two hemophiliacs (31%) circulated
cryoglobulins (median levels, 166 mg/L; range, 66 to 480) predominantly
type III (62%; and 29% type II). None of the patients had clinical
signs or symptoms of systemic vasculitis. Cryoglobulinemic patients had
more often serum HCV-RNA (95% v 80%, P < .05),
rheumatoid factor (20% v 6%, P < .05), higher levels of IgG (2,354 ± 682 mg/dL v 1,928 ± 557 mg/dL,
P < .0005) and IgM (323 ± 226 mg/dL v 244 ± 243 mg/dL, P < .05), and lower levels of serum C4 (19 ± 8 mg/dL v 24 ± 8 mg/dL, P < .05) than patients
without cryoglobulins. The risk of producing cryoglobulins was greater
for 114 patients circulating HCV-RNA than for 21 nonviremic patients (odds ratio [OR] = 4.9, 95% confidence
interval [CI] = 1.1 to 22.0) and for the 31 patients with longer
exposure to HCV (more than 26 years) than for the 24 patients with
shorter (17 years or less) exposure (OR = 4.4 95% CI = 1.1 to
18.0). In conclusion a large number of multitransfused hemophiliacs
with chronic HCV infection circulated serum cryoglobulins but none had
clinical signs or symptoms of vasculitis. The risk of developing cryoglobulins parallels the duration of exposure to HCV.
Blood, Vol. 92 No. 2 (July 15), 1998:
pp. 516-519
© 1998 by the American Society of Hematology.
