Role of Platelet Indices and Thrombopoietin (TPO) Serum Levels in the Differential Diagnosis of Thrombocytopenia

Abstract

Background: The differential diagnosis of an isolated thrombocytopenia may be challenging, especially when it comes to differentiate immune thrombocytopenia (ITP) and an isolated thrombocytopenia in the context of bone marrow (BM) failure, in particular myelodysplastic syndromes (MDS); in such cases a BM examination is usually performed. It is known that thrombopoietin (TPO) serum levels are low in patients with ITP, while they are increased in case of amegakaryocytic thrombocytopenia. Furthermore, some platelet indices such as immature platelet fraction (IPF) may help to discriminate between hyporigenerative and consumption thrombocytopenia. Aim: The aim of this study was to compare TPO serum levels and platelet indices in patients with thrombocytopenia of different etiologies. Based on pathogenesis, we chose 3 groups of patients: ITP, amegakaryocytic thrombocytopenia (aplastic anemia (AA) or post-chemotherapy (CHT)) and thrombocytopenia in MDS and acute myeloid leukemia (AML). Although the diagnosis of amegakaryocytic thrombocytopenia and AML is straightforward with BM examination, we included patients with these diseases as a proof of concept and training set for our findings. Methods: This was a monocentric, retrospective, explorative study. Blood samples of patients with a platelet count < 100x109/L were collected. IPF, mean platelet volume (MPV), platelet distribution width (PDW), plateletcrit (PCT), platelet large cell ratio (P-LCR) were obtained using Sysmex XN-1000 hemocytometer (Sysmex Corporation). TPO serum levels were measured with a quantitative sandwich ELISA (R&D Systems). Microsoft Excel software was used for descriptive statistical analysis. Anova and Student's t-test were used for comparisons between groups. A p-value <0.05 was considered statistically significant. Results: We enrolled 84 patients: 50 ITP, 22 AML/MDS (13 AML, 9 MDS), 12 AA/post-CHT (4 AA, 8 post-CHT). Results are reported in Table 1. Neither mean platelet count (p=0.20) nor PCT (p=0.44) were significantly different between the three groups. Mean TPO serum levels were higher in patients with AA/post-CHT compared to ITP and AML/MDS groups (p<0.001). All patients in AA/post-CHT group had a TPO serum level >500 pg/mL, this value was never reached in patients with ITP and AML/MDS. TPO serum levels were higher in AML/MDS patients compared to ITP patients (p<0.001). While TPO serum levels were available for all patients, platelet indices were not, due to technical issues. IPF was available in 46/50 ITP patients, 20/22 AML/MDS and 8/12 AA/post-CHT, and it was higher in ITP patients if compared to AA/post-cht (p=0.021) and AML/MDS (p=0.0045). MPV, PDW and P-LCR were available in 27/50 ITP patients, 12/22 AML/MDS and 9/12 AA/post-CHT: they were higher in ITP patients than in the other groups (AML/MDS p=0.0185, AA/post-CHT p=0.017). In our cohort, patients with TPO ≥250 pg/mL and IPF <12% had a higher probability to belong to AML/MDS group (TPO: OR 0.08, 95% CI 0.02-0.32; IPF: OR 0.19, 95% CI 0.06-0.59). These findings were confirmed by multivariate analysis (IPF: p-value = 0.0185, CI 0.8647-0.9868; TPO: p-value = 0.004, CI 1.002-1.011). The other platelet indices were not included in this analysis due to the paucity of data. No correlation was found between platelet count, TPO and IPF in ITP patients. Of note, no differences were observed in terms of platelet count, TPO serum levels ad IPF between patients with AML and MDS. Conclusions: Our findings confirm that, in patients with the same platelet count, those with consumptive thrombocytopenia have higher IPF and lower TPO levels, while patients with amegakaryocytic thrombocytopenia have higher TPO levels and lower IPF. While TPO levels alone can distinguish amegakaryocytic thrombocytopenia from other etiologies, these preliminary data suggest that by combining IPF and TPO, patients with consumptive thrombocytopenia can be distinguished from MDS patients. This could be useful to spare BM examination in selected cases, or as an additional tool when the diagnosis remains uncertain also with BM examination. These data need to be confirmed in larger cohorts. The role of the other platelet indices, and the technical issues in their determination, needs further studies. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal