HCV‐associated thrombocytopenia: clinical characteristics and platelet response after recombinant α2b‐interferon therapy

Abstract

Summary. Hepatitis C virus (HCV) has been proposed as a possible causative agent of chronic thrombocytopenia. We investigated HCV infection in a series of 51 unselected Spanish patients with chronic acquired thrombocytopenia. Anti-HCV and HCV viraemia were detected in 13/51 (22´5%) of cases; this prevalence was particularly significant when compared with HCV seropositivity in agematched controls (0´4%). Anti-HCV-positive patients, four men and nine women with a median age of 59´3 years (range 36±72), had a mean platelet count of 55´8 Â 10 9 /l (range 12±96). Only one of our HCV-positive thrombocytopenic patients had hypersplenism. Platelet-associated IgG (PAIgG) was negative, as measured by immunofluorescent flow cytometric analysis in 11/13 HCV-positive thrombocytopenic patients. Thus, thrombocytopenia in our HCV-positive patients appeared to be non-autoimmune mediated. In six patients, a trial of recombinant a2b-interferon (IFN-a) given at a dose of 3 MU three times per week for 6±24 months gave a durable (. 1 year) and significant increase in platelet count in all six patients. The maximum increase occurred after 6 months of IFN-a therapy. In conclusion, the ability of IFN-a to increase platelet counts in HCV-positive thrombocytopenic patients supports mechanisms involving a direct role for HCV inhibiting platelet production.

Viral-Associated Immune Thrombocytopenic Purpura

“…29 Similar responses to IFN-α therapy alone have been reported in HIV-seronegative patients infected with HCV. 30,31 An unblended open label trial of IFN-α in a cohort of predominately homosexual men documented responses in 9 of 16 patients, with responses occurring as early as 2 weeks after the initiation of treatment. 32 Such rapid responses preclude the possibility that improvement in the platelet count is due solely to suppression of concomitant HCV infection.…”

“…30,31,37 Epidemiology Six cross-sectional studies have reported serologic evidence of HCV infection in 159 of 799 (20%) patients with a clinical diagnosis of CITP (Table 1). 30,31,[37][38][39][40] In the largest series published to date, HCV antibodies were identified in 76 (30%) of 250 patients fulfilling the ASH guideline criteria for CITP. 31 There were significant differences in demographic characteristics of patients with HCV-positive compared with HCV-negative CITP.…”

“…42 The prevalence of HCV-positive CITP patients in the cohort studies may be indirectly related to the background prevalence HCV reported in the general populations studied. 30,31,38 Pathophysiology A variety of pathogenic mechanisms have been implicated in CITP related to chronic HCV infection. The binding to and possible infection of platelets 43 and megakaryocytes 44 by HCV has been reported.…”

“…31 Four Approximately half of adult CITP patients with HCV treated with INF-α therapy responded with a rise in platelet count. 30,31,47,51 Four of 5 HCV-positive patients treated with interferon-alpha (IFN-α) responded with increased platelet counts. 41,47 Responders to IFN-α could be distinguished from the non-responder by a decrease in HCV quantitative RNA, hepatic transaminases and cryoglobulins.…”

Hepatitis C virus and autoimmunity

“…Another contributing factor in the development of thrombocytopenia seems to be the bone marrow suppression caused by HCV itself or IFN-α treatment. Thrombocytopenia in patients with HCV infection shares many clinical features of idiopathic thrombocytopenic purpura [113,114]. Several pathogenetic hypotheses exist.…”