Chronic hepatitis C virus (HCV) infection has also been associated with the development of several extrahepatic alterations, including thrombocytopenia, and a variety of pathogenic mechanisms are reported to be implicated in this hematological abnormality. Different studies have succeeded in detecting HCV in platelets with discrepant results. Moreover, most of the studies on HCV-associated thrombocytopenia have failed to provide data concerning the infecting genotype, a factor with prognostic implication in chronically HCV-infected patients. To determine whether thrombocytopenia is an extrahepatic alteration dependent on particular HCV genotypes, and to assess the relationship between thrombocytopenia and detection of HCV-RNA (positive strand) in platelets from patients with chronic HCV infection, 106 anti-HCV+/HCV-RNA+ patients (57 thrombocytopenic and 49 non-thrombocytopenic) were prospectively studied. The infecting genotype was analyzed from sera by using direct nucleotide sequencing of the polymerase chain reaction (PCR) products from core region. Genotypes 1a, 1b, and 3a were more prevalent in our patients, and no association between these genotypes and thrombocytopenia was observed ( p=0.891). HCV-RNA was detected in platelets by reverse transcriptase (RT)-nested PCR in the 5' non-coding region with a higher frequency (60%) in thrombocytopenic patients than in non-thrombocytopenic subjects (35%, p=0.017), suggesting that HCV is directly involved in the process that, at least in part, leads to thrombocytopenia.

Since the identification of hepatitis C virus (HCV) in 1989 as a causative agent for a number of the extrahepatic alterations related to HCV infection an underlying immune mediated pathogenetic mechanism has been postulated. HCV-associated thrombocytopenia may be considered complex and multifactorial in origin, since different mechanisms have been implicated in its pathophysiology. With respect to autoimmune thrombocytopenia in chronic HCV infection, the detection of specific antibodies against platelet glycoproteins have been reported only in a few studies, but no systematic study has been carried out. We examined the clinical, laboratory, and virological characteristics of a case series of 10 patients with autoimmune thrombocytopenia (platelet count <150.0 x 10(9)/L) related to chronic HCV infection. Cases, six males and four females, aged 57.1 +/- 12.6 years, presented high titers of antibodies against platelet glycoprotein (GP) IIb/IIIa, GP Ia/IIa, and/or GP Ib/IX, and no other mechanism involved in the pathogenesis of HCV-associated thrombocytopenia was identified. Furthermore, cases were not associated with particular HCV genotype. Complete platelet response was observed in two patients treated with pegylated interferon plus ribavirin, and partial platelet response was seen in two patients treated with anti-D Ig and one patient treated with corticosteroids. These findings indicate that an autoimmune mechanism may play a role in the pathogenesis of HCV-associated thrombocytopenia in a proportion of these patients.

The development of clotting factor inhibitor autoantibodies is rarely observed, but can result in a potentially life-threatening haemorrhagic disorder. These acquired inhibitors are most frequently against factor VIII (FVIII), whilst the detection of inhibitors against other clotting factors is rarer. Inhibitors against FVIII and FIX are mostly observed in patients with classical hereditary haemophilia after receiving factor replacement therapy. We report a rare case of acquired FVIII and factor IX (FIX) inhibitors in a single, non-haemophilic patient with chronic hepatitis C virus (HCV) infection who was receiving antiviral treatment with pegylated interferon plus ribavirin. The FVIII and FIX activities were <1% and high titres of inhibitors autoantibodies were found in his serum samples. After achieving a sustained virological response, combined immunosuppression with oral corticosteroids (prednisone) and azathioprine was introduced, eradicating the inhibitory autoantibodies. The development of these inhibitors in association with antiviral therapy for chronic hepatitis C is poorly understood, and particular attention must be given to HCV-infected patients with worsening coagulopathy, particularly if coexistent with treatment related thrombocytopenia.

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