Hepatitis C virus-associated thrombocytopenia: a controlled prospective, virological study

Abstract

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.

Hepatitis C virus interacts with human platelet glycoprotein VI

“…Several mechanisms have been proposed as contributing to thrombocytopenia: sequestration of platelets in the enlarged spleen (Sanjo et al, 2003); platelet destruction mediated by platelet-associated IgG possibly leading to the sequestration in the reticuloendothelial system and also related to hypersplenism (Nagamine et al, 1996;Pockros et al, 2002;Sanjo et al, 2003); impaired hepatic production of thrombopoietin (Ishikawa et al, 1998;Martin et al, 1997;PeckRadosavljevic et al, 1997) and a direct viral effect since a positive correlation between thrombocytopenia and HCV association with platelets has been found (de Almeida et al, 2004).…”

“…Several investigators have reported HCV association with platelets (de Almeida et al, 2004;Floreani et al, 1996;Li et al, 1994;Nagamine et al, 1996;Silva et al, 1992;Takehara et al, 1994). We have previously shown the interaction of immunoglobulin (Ig) G-free and IgG-complexed HCV with platelets in chronically infected patients (Hamaia et al, 2001).…”

“…Viral interaction with platelets is well recognized, as it has been described for other viruses such as herpes simplex virus (Forghani & Schmidt, 1983), Vaccinia virus (Bik et al, 1982), Human immunodeficiency virus 1 (HIV-1) (Lee et al, 1998(Lee et al, , 1993Olinger et al, 2000), echovirus 1 (Xing et al, 2004), hantavirus (Gavrilovskaya et al, 1998) and the flavivirus dengue type 2 (Wang et al, 1995) among others. Several mechanisms have been proposed as contributing to thrombocytopenia, but recently a positive correlation between thrombocytopenia and HCV association with platelets was described (de Almeida et al, 2004), suggesting a direct viral effect on platelet count.…”

“…Viral interaction with platelets is well recognized, as it has been described for other viruses such as herpes simplex virus (Forghani & Schmidt, 1983), Vaccinia virus (Bik et al, 1982), Human immunodeficiency virus 1 (HIV-1) (Lee et al, 1998(Lee et al, , 1993Olinger et al, 2000), echovirus 1 (Xing et al, 2004), hantavirus (Gavrilovskaya et al, 1998) and the flavivirus dengue type 2 (Wang et al, 1995) among others. Several mechanisms have been proposed as contributing to thrombocytopenia, but recently a positive correlation between thrombocytopenia and HCV association with platelets was described (de Almeida et al, 2004), suggesting a direct viral effect on platelet count.Platelets do not express CD81 (Levy et al, 1998), SR-BI (Rhainds & Brissette, 2004), DC-and L-SIGN (van Kooyk & Geijtenbeek, 2003) or the classical LDL-R (Korporaal et al, 2004;Pedreno et al, 1992), which are putative HCV receptors (Agnello et al, 1999;Gardner et al, 2003;Lozach et al, 2003; Monazahian et al, 1999;Pileri et al, 1998;Pohlmann et al, 2003;Scarselli et al, 2002). Thus, other molecule(s) might mediate the interaction between HCV and platelets.…”

Associations among clinical, immunological, and viral quasispecies measurements in advanced chronic hepatitis C

“…11,37,38 QS diversity showed a negative correlation with platelet counts and a positive correlation with serum ALT in our study cohort. Both thrombocytopenia and hepatocyte injury in chronic HCV infection have been attributed to viral and immunological mechanisms, 39 and increased viral QS diversity has the potential to affect both components. Although these correlations were statistically significant, it should be noted that the effects were weak (r values of Ϫ.…”