Reticulated platelet fraction levels in HIV infected individuals with thrombocytopenia

Date
2011-01-26
Authors
Vaughan, Jenifer Leigh
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Abstract
Thrombocytopenia is common among individuals infected with HIV, with a wide range of possible causes. It often necessitates the performance of a bone marrow investigation in order to assess megakaryocyte activity and to exclude the presence of bone marrow infiltration. Unfortunately, meaningful interpretation of the bone marrow findings is often hampered by the frequent co-existence of multiple potential pathogenic processes. For example, megakaryocyte numbers are often well preserved (even in the presence of marrow infiltration), but show a degree of dysplasia, (suggesting that ineffective megakaryopoiesis is contributing to the thrombocytopenia). In addition, processes associated with peripheral platelet consumption (such as immune-mediated platelet destruction or disseminated intravascular coagulation) are also common, and the mechanism causing thrombocytopenia is therefore often obscure. Because this mechanism is of clinical interest, (in that it guides the selection of the most appropriate therapy), a functional test of megakaryocyte activity would be of potential value. The IPF is a platelet parameter measured on the Sysmex XE-5000 haematology analyzer, which quantifies the number of reticulated platelets, and has been shown to be a good reflector of underlying bone marrow megakaryocyte activity. The objectives of this study were therefore to measure the IPF level in HIV-positive patients with thrombocytopenia who had undergone a bone marrow investigation, and to correlate the IPF with the bone marrow morphology findings and other clinical variables of interest (including the CD4 count, the HIV viral load and the presence of opportunistic infections or malignancies). The IPF was also assessed as a tool to predict the short term platelet count response to the therapy initiated by the attending clinician. 78 patients were enrolled, of whom 38 (49%) had mycobacterial infection, 12 (15%) had ITP/TTP and eight (10.3%) had a malignancy. CD4 counts were available in 70 patients, of whom 63 (90%) had AIDS. Thirty seven patients (47%) were found to have an IPF level greater than 7.7% , with an overall population mean IPF level of 9.5%. A strong relationship was identified between the IPF and the platelet count, with 81% of patients with grade four thrombocytopenia having an IPF level greater than 7.7% (mean IPF=14%), as compared to only 8% of grade one thrombocytopenia (mean IPF=6%). 67% of patients with hypocellular or extensively infiltrated marrow had a low IPF (≤ 7.7%)(mean=7%), as compared to only 25% of patients with ITP/TTP (mean=14.8%). A higher proportion of patients with low viral load levels had a low IPF as compared to those with higher viral loads, possibly due to the apparent sparing of patients with low viral loads from grade four thrombocytopenia. In contrast, the presence of a significant degree of megakaryocyte dysplasia, a very low CD4 count or the presence of mycobacterial infection did not affect the IPF distribution, suggesting that the underlying mechanism causing thrombocytopenia in these subgroups was heterogeneous. An IPF level greater than 10% predicted a partial platelet count response (as defined as an improvement by greater than 50% of the baseline platelet count to a minimum level of 20x10^9/l), with a specificity of 81% and a positive predictive value of 79%, while an IPF level less than 6% had a specificity of 89% and a positive predictive value of 70% for a complete failure to show a platelet count response to the therapy instituted. Limitations of the IPF illuminated in this study include a loss of reliability in any circumstance in which the platelet count as measured by optical fluorescence may be in question, and includes disorders associated with profound red cell fragmentation and some malignancies. The cause of thrombocytopenia is concluded to be very heterogeneous in thrombocytopenic patients with AIDS, even among patients with a unifying diagnosis (such as mycobacterial infection). The IPF is therefore a useful tool to assist the morphologist in interpreting the bone marrow findings in this clinical setting, as well as in predicting the short term platelet count response to therapy.
Description
MMed, Haematology. University of the Witwatersrand, Faculty of Health Sciences
Keywords
thrombocytopenia, blood platlets
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