Mechanism of Thrombocytopenia in Hepatitis C as Determined by the Immature Platelet Fraction.

Thrombocytopenia is a frequent complication in patients with hepatitis C. Possible mechanisms include hypersplenism, immune-mediated platelet destruction, and drug-induced impairment of platelet production. The immature platelet fraction (IPF), determined on an automated blood cell analyzer (Sysmex XE-2100), has been shown to be useful in differentiating consumptive and aplastic causes of thrombocytopenia. We studied 31 patients known to have hepatitis C, 21 with thrombocytopenia (platelet count <100,000/uL) and 10 with normal platelet counts (>140,000/uL). None of the patients was taking interferon. Blood samples were drawn for CBC with platelet count, IPF (%), and thrombopoietin (TPO) assay (Quantikine TPO ELISA). The presence or absence of splenomegaly and liver function test results were noted. In the thrombocytopenic group IPF was elevated above the upper limit of the reference range (>7.1%) in 12/21 (57%) patients, suggestive of peripheral platelet consumption. TPO levels (known to correlate inversely with platelet/megakaryocyte mass) were within the normal range (<146pg/mL) in 11/12 (92%) of these patients, implying adequate megakaryocyte mass, which is further evidence of peripheral platelet consumption in this group. Splenomegaly was present in 8 of these 12 patients, suggesting that hypersplenism may be the mechanism for thrombocytopenia in this sub-group. IPF was within normal limits in 9/21 (43%) of the thrombocytopenic patients, implying either decreased platelet production or ineffective thrombopoiesis as the major cause of thrombocytopenia in this group. TPO levels were within the normal range in 8/9 (89%) of these patients, again implying adequate megakaryocyte mass, and suggesting that ineffective or impaired thrombopoiesis, rather than decreased platelet production, may be the major mechanism for thrombocytopenia in this group. Splenomegaly was present in 7 of these 9 patients, thus hypersplenism cannot be ruled out as at least a contributory factor in this sub-group (in spite of normal IPF values). One patient in this group had an elevated TPO level, suggestive of megakaryocyte hypoplasia. In the group of patients with normal platelet counts IPF was within normal limits in 8/10 patients, and minimally elevated in the other 2 patients. TPO levels were within normal limits in this entire group, and no patients in this group had splenomegaly. In conclusion, our findings suggest that peripheral platelet consumption is a major cause of thrombocytopenia in patients with hepatitis C (at least 57% of patients in this study), predominantly secondary to hypersplenism. Other possible causes of peripheral platelet consumption (in those without splenomegaly) include immune-mediated platelet destruction secondary to antibodies, immune complexes or drugs. In the remaining patients (43% in this study) ineffective thrombopoiesis may be the major mechanism of thrombocytopenia, possibly related to the effect of virus, cytokines, drugs or antibodies on thrombopoiesis, in the presence of adequate megakaryocytes in the marrow. Decreased platelet production (megakaryocyte hypoplasia) appears to be an unusual mechanism of thrombocytopenia in these patients.