Alfa-2a recombinant interferon in HIV associated thrombocytopenia.

A male homosexual (aged 30) presented with bruising and gingival bleeding. His platelet count was 5 x 109/l and his bone marrow contained increased numbers of megakaryocytes. An impalpable spleen and absence of antinuclear-factor supported a diagnosis of immune thrombocytopenia. Prednisolone 60 mg daily raised the platelet count to 66x 109/1, but he became jaundiced with "hepatitic" liver function values. He had been a low grade hepatitis B carrier (hepatitis B surface antigen titre on radioimmunoassay 6-25, e antigen negative, and core antigen IgM equivocal) and was positive for HIV antibodies by Western blotting. After six weeks of prednisolone the hepatitis B surface antigen titre had risen to 134 (haemagglutination >8192) and he became positive for e antigen and core antigen IgM, findings consistent with reactivation of hepatitis B. Steroids were discontinued. The platelet count fell but responded (250x 109/l) to intravenous immunoglobulin 0-4 g/kg daily for five days. The effect was short lived and he required repeated intravenous immunoglobulin for a platelet count of less than 35x 109/l. After mild trauma he experienced right loin pain and profuse haematuria, indicating renal haemorrhage, which was managed by platelet infusions and intravenous immunoglobulin. Liver biopsy at six months showed chronic active hepatitis. Recombinant alfa-2a interferon, 3 MU on alternate days, was given subcutaneously. Core antigen IgM fell to equivocal values, e antigen became negative, and e antibody appeared. Liver function values became near normal. The platelet count, measured weekly, rose from 62 (SD 98)x109/l to 110 (49)x 109/l; the number ofweeks the platelet count was below 35 x 109/1 fell from 10 to 0 and the requirement for intravenous immunoglobulin fell from 15 days to four days over this period, being given when the platelet count appeared as if it might reach less than 35 x 109/l (figure). Interferon was continued for five months and then stopped; the platelet count fell to less than 35 x 109/1 and further intravenous immunoglobulin was required. Interferon was restarted after three months. The platelet count rose again, and, although the rise in the mean weekly count was not as pronounced (69 (27)x 109/l), he did not require any further intravenous immunoglobulin over the four months, and the count did not fall below 35 x 109/1. Platelet associated immunoglobulin was measured before we started the second course of interferon and during interferon treatment using a fluorescence activated cell cytometer (Epics C, Coulter Electronics). Platelets obtained by centrifugation from blood stored in edetic acid and washed in phosphate buffered saline were then fixed by 1% paraformaldehyde to prevent in vitro adsorption of immune complexes. They were then reacted with fluorescein isothionate conjugated antihuman IgG and IgM. Platelet associated immunoglobulin was calculated as % fluorescence using a standard curve. At the start of the second course ofinterferon, when the platelet count was 28x 109/l, concentrations ofboth platelet associated IgG and IgM were raised (25 ng/106 platelets (normal <4-85) and 15 ng/106 platelets (normal <1 respectively). These concentrations fell with the platelet response. Immune complexes were not detected on the platelets or in serum.