ATLANTAIt appears that HIV-related thrombocytopenia can
be corrected using a form of thrombopoietin to improve platelet
production, Richard A. Carter, MD, of Emory University, said at the
ASH meeting. He reported results of Amgens PEG-rHuMGDF
(pegylated recombinant human megakaryocyte growth and development
factor) in six HIV-infected thrombocytopenic patients.
He explained that thrombocytopenia in HIV patients is common,
occurring in about one-third of individuals. It is due to a
combination of shortened platelet lifespan, enhanced platelet splenic
sequestration, and ineffective platelet production by megakaryocytes.
A low platelet count generally leads to increased megakaryocyte
production, but HIV can directly infect the megakaryocytes and induce apoptosis.
Dr. Carter noted that HIV also increases levels of endogenous
thrombopoietin and increases the megakaryocyte mass, which increases
platelet turnover but also results in defective delivery of platelets
to the periphery.
The researchers hypothesized that thrombopoietic stimulation with
PEG-rHuMGDF would normalize peripheral platelet counts in
HIV-infected patients by improving the effectiveness of platelet
production and stimulating megakaryocyte proliferation.
For the first month, patients were randomized to receive placebo or
PEG-rHuMGDF, 5 µg/kg SC twice weekly. Placebo patients were
given the growth factor after the first month, and all patients
received it for 4 months.
In all patients, platelet counts normalized in response to this
dose, in most cases within 2 weeks, Dr. Carter said. This
occurred despite only a modest increase in platelet lifespan and
reflected a striking amplification in platelet turnover.
The increase in peripheral platelet counts was 10-fold and was not
associated with increased megakaryocyte mass, development of
anti-PEG-rHu-MGDF antibodies, or increased HIV viral load.
Platelet counts were sustained throughout the 16 weeks of therapy but
returned to thrombocytopenic baseline within 2 weeks after
discontinuation. This approach will require maintenance
therapy, he said.