Abstract
BACKGROUND. ITP is an autoimmune disorder in which autoantibodies (Ab) reacting to platelet glycoproteins (Gp) mediate immune destruction of platelets. In most cases the cause is unknown, but chronic infections such as hepatitis C, studied here, are often associated with ITP (ITP-C). In ITP-C, it is not clear whether platelets are destroyed by viral immune complex or by Gp Ab, as in classic active ITP (ITP-A). Antiviral therapy may not induce remission in ITP-C, so its management remains problematic. We investigated Gp Ab in ITP-C vs. ITP-A, and evaluated efficacy of IL-11 in a group of patients (pts) with ITP-C. A previous study found that IL-11 is ineffective in treatment of ITP-A [Am J Hematol, 2001; 66: 172–7].
METHODS. We studied 35 pts with ITP-A (19F, 16M, mean age 53yr, mean platelet count 61,000/μL) and 15 with ITP-C (9F, 6M, mean age 61yr, mean platelet count 66,0000/μL). Lab tests included CBC, platelet counts, liver function tests, HCV-RNA, and clotting factor activity (FVIII & vWF). Ab against Gp were assayed by PAICA. Six pts with ITP-C were treated with IL-11 (50 mg/kg) for 7 days to 9 mo’s. In four, clinical courses were followed after discontinuing IL-11.
RESULTS. As shown in Table 1, the prevalence of all 3 Gp Ab (IIb/IIIa, Ib/IX, and IV) was significantly more frequent in ITP-C than ITP-A, for both IgG (p≤ 0.007) and IgM (p=0.005). Mean titers of Ab were also higher in ITP-C than ITP-A, but only IgM Ab were significant (p<0.001). vWF and FVIII were above normal in both groups, but the only significant difference between the groups was in vWF, higher in ITP-C than ITP-A in terms of frequency of elevation (71% vs. 34%, p=0.002) and titer (2.63 U/mL vs. 1.69 U/mL, p=0.005).
Results of IL-11 treatment. In the six ITP-C pts treated with IL-11, platelet counts rose in all cases in 1–2 wk (mean pre = 61,000; mean post = 112,000/uL), and liver enzymes normalized in 1–2 wk. We also found an antiviral effect of IL-11: mean HCV-RNA fell from 3.167 x106 to 0.741 x106 after 1–3 wk. In only 1 pt did the HCV-RNA go up during the treatment, and began to decline when IL-11 was discontinued. In all 4 pts followed after discontinuing IL-11, platelet count dropped after 1–3 wk (from 112,000 to 90,000/μL). In 2 pts, liver enzymes rose after 1–3 wk but remained normal in the other two. HCV-RNA assay was repeated after 3–8 mo’s in 3 pts; mean value was 1.925 x106. In 2 pts, Gp Ab disappeared following treatment.
CONCLUSIONS. (a) In excess of 90% of pts with ITP-C had specific Gp Ab. This indicates that ITP in hepatitis C is autoimmune-mediated similar to classic ITP, not immune-complex mediated. (b) The high incidences of elevated FVIII and vWF could be secondary to inflammation, and may play a role in limiting bleeding. (c) Our preliminary data on use of IL-11 in ITP-C is encouraging, as most responded favorably. Treatment was associated with decreased levels of HCV-RNA and Gp Ab.
Tab 1 ITP-A, n=35 ITP-C, n=15 p value Gp IIbIIIa IgG/IgM (% elevated) 60/54 92/91 0.0007/0.005 Gp IbIX IgG/IgM (% elevated) 51/46 91/91 0.007/0.005 Gp IV IgG/IgM (% elevated) 59/40 100/90 0.0001/0.005 IIbIIIa IgG/IgM (Titre) 3.27/2.47 3.59/10.4 n.s./0.001 IbIX IgG/IgM (Titre) 2.59/2.35 3.37/8.82 n.s/0.001 IV IgG/IgM (Titre) 2.93/2.09 3.56/7.18 n.s./0.001 vWF (% elevated/titre) 34/1.69 71/2.63 0.002/0.005
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