Thrombocytopenia (decreased platelet counts) is a common HIV-related disorder. HIV-related thrombocytopenia bears some similarity to idiopathic thrombocytopenic purpura (ITP). However, it is distinct from ITP in several respects, including its tendency to respond to AZT treatment. Ballem et al. report that both platelet survival and platelet production (by megakaryocytes) are decreased in HIV-related thrombocytopenia. This latter finding, together with the in vitro observation that HIV can infect megakaryocytes, suggest that HIV infection of megakaryocytes may be a direct cause of thrombocytopenia.
Treatment Results:
Several groups (Hymes et al., Swiss Group for Clinical Studies on AIDS, Jackson et al.) have reported that AZT can rapidly increase platelet counts in patients with HIV-related thrombocytopenia. This increase generally occurs within several weeks of iniliating treatment, but is not sustained after treatment cessation.
In patients with AZT-resistant thrombocytopenia, alpha interferon [IFN-(lambda)] has been reported to be a safe and effective treatment. Marroni et al. treated 15 patients with platelet counts less ihan 25,000/mm3 who were refractory to 1 month of full dose (1,000 mg/day) AZT. Patients were randomized to either IFN-(lambda), (3 million units) or placebo three times a week subcutaneously for 4 weeks, followed by a 4-week washout period, then switched to the altemative treatment. Complete responses were observed in 12/15 patients.
Rarick et al. treated 14 adults with HIV-related thrombocytopenia with IVIG (1 g/kg on days 1, 2 and 15). The median platelet count increased from 17,000/mm3 at baseline to a maximum of 220,000/mm3. All patients had responded by day eight, but the effect was transient, with the median platelet count declining to 40,000/mm3 by day 15. The investigators suggested that IVIG may be used in patients with HIV-related thrombocytopenia who required an immediate increase in platelet count.
Results from an open label study of WinRho, a freeze-dried gamma globulin, have been reported (Bussel et al.). Eleven children and 52 adults with HIV and thrombocytopenia (Platelet counts < 30,000/mm3). AIDS patients were treated with 100 to 375 IU/kg WmRho for an average of 7.3 courses over a mean period of 407 days. 57/63 responded (median increase > 20,000/mm3) during the first six courses of therapy for an overall response rate of (90%). The overal mean change in plateiet count for six courses was 60,900/mm3. Total infusion time is 3-5 minutes.
Kemeny et al. reported the results of a retrospective chart review of 22 HIV-infected patients who underwent splenectomy. The patients were classified as having ITP (n = 13) or a splenic infiltrative process (MAI, KS, or lymphoma, n = 9). The investigators defined a complete response to the surgery to be a platelet count >150,000 one month post-operatively. Complete responses were observed in 11/13 patients with ITP and 6/9 with splenic infiltrative processes.
REFERENCES:
Hymes KB et al. The effect of azidothymidine on HIV related thrombocytopenia. NEJM 318: 516-7, 1988.
Jackson GG et al. Human immunodeficiency virus antigenemia in the acquired immunodeficiency syndrome and the effect of treatment with zidovudine, Ann Int Med 108: 175-80, 1988.
Kemeny MM et al. Splenectomy in patients with AIDS and AIDS-related complex. AIDS 7:1064-7, 1993.
Rarick MU et al. Intravenous immunoglobulin in the treatment of human immunodeftciency virus-related thrombocytopenia. Am J Hematol 38: 261-6, 1991.
Marroni M et al. Interferon-(lambda) is effective in the teaatment of HIV-1-related, severe, zidonvudine-resistant thrombocytopenia. Ann Intem Med 121:423-429, 1994.
Swiss Group for the Clinical Studies on AIDS: Zidovudine for the treatment of tombocytopenia associated with the human immunodeficiency virus (HIV). Ann Int Med 109: 718-21, 1988.
OTHER REPORTS:
Lessinger et al. Role of splenectomy in the management of hemophilic patients patients with human immunodeficiency virus-associated immunopathic thrombopenic purpura. Am J Hematol 40:207-9,1992.
Louache F et al. Infection of megakaryocytes by human immunodeficiency virus in seropositive patients with immune thrombocytopenic purpura. Blood 78:,1697-705, 1991.
Nieuwenhuis HK and Sixma JJ. Thrombocytopenia and the neglected megakaryocyte (editorial). NEJM 327: 1812-3, 1992.
Ballem PJ et al. Kinetic studies of the mechanism of thrombocytopenia in patients with human immunodeficiency virus infection. NEJM 327: 1779-84, 1992.
Bussel JB et al. Intravenous anti-D treatinent of immune throbocytopenic purpura: malysis and efficacy, toxicity, and mechanism of effect. Blood 77:1884-93, 1991.
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