Diagnostic predictive value of platelet indices for discriminating hypo productive versus immune thrombocytopenia purpura in patients attending a tertiary care teaching hospital in Addis Ababa, Ethiopia

Simple, inexpensive and non invasive tests like MPV have been reported to identify causes of thrombocytopenia as hyperdestructive or hypoproductive with sufficient predictive capacity, sensitivity and specificity [4, 5, 7]. In the study reported herein, three platelet indices MPV, PDW and P-LCR were analyzed for their diagnostic predictive capacity in different patients with thrombocytopenia. Consistent with the above studies [4, 5, 7], there was a significant difference in MPV between hypoproductive and ITP patients. Moreover, PDW and P-LCR had significant differences between the two patient groups and better discriminating potential.

Niethammer et al. reported that maximum of the histogram, that is the highest peak of the platelet volume distribution curve, has better efficiency than MPV in identifying thrombocytopenia caused by ITP and that resulted from decreased platelet production secondary to receiving chemotherapy [9]. MPV was able to predict the presence of bone marrow metastasis in solid tumor patients with 85 % PPV and 90 % NPV [10]. There is a growing interest in the use of platelet markers in discriminating different forms of thrombocytopenia. Monteagudo et al. measured reticulated platelets by using flow cytometry and showed this parameter has high sensitivity and specificity in identifying thrombocytopenia with increased thrombopoietic activity [11].

Studies showed immature platelet fraction (IPF) measured by Sysmex XE2100 had better sensitivity and specificity in the diagnosis of hyperdestructive thrombocytopenia like ITP and TTP [12, 13]. Though this IPF is one of the out puts from the Sysmex XE2100, such kind of automated analyzer is not available in our country for routine hematology analysis. Sysmex XT 2000i is the model currently available in our country which was also used in this study.

The most common cause of thrombocytopenia in hypoproductive patients was bone marrow suppression secondary to CML chemotherapy. This could be due to the predominance of CML as the leading type of leukemia in Ethiopia which accounts for more than 57.8 % of all the leukemia causes [14].

There was uneven distribution of sex among the study subjects, where females were almost twice than males in ITP, on the other hand males were twice in hypoproductive patients. This may be due to some epidemiological differences in the incidence and prevalence of chronic ITP which is more common in females (in particular in women of child bearing age) compared to males with ratio of 2–3 to 1 [15, 16], while CML is more common in old ages and in males than females with ratios of 1.5–1.8 to 1 [17, 18].

MPV values of 9.7 fl for the hypoproductive group and 12.4 fl for ITP patients observed in our study is much higher than those reported from UK [5], Taiwan [6] and India [19]. In all these studies, they showed that MPV was significantly different between hypoproductive and hyperdestructive patients. However, the reported mean MPV values are 8.1 fl and 9.8 fl in the UK study [5], 7.2 fl and 8.8 fl in the Taiwan [6] and 7.3 fl and 8.62 fl in the Indian study [19] in hypoproductive and hyperdestructive patients, respectively.

The first possible explanation for such differences between this and the above studies could be the kind of automated hematology analyzers that is used for enumerating the platelets. A study conducted by Kaito et al. In Japan using Sysmex-XE2100 analyzer (Kobe, Japan) reported a mean MPV of 10.2 fl in aplastic anemia and 12.2 fl in ITP patients [7], whose values are closer to our finding for ITP. A similar finding was also reported from a study conducted by Ntaios et al. who also used sysmex-XE2100 automated analyzer [4]. Ntaios et al. emphasized that the higher values of the platelet indices in their study compared to others could be due to a difference in hematology analyzers. Large or giant platelets could be excluded from the platelet count with instruments which use impedance method like coulter STKS [6] and coulter Gen-S [5] used by the above studies, but the Sysmex XT2000i and XE2100 series also employ optical fluorescence detection method [20].

The second possible reason could be an actual difference in the platelet indices among population from country to country. A study by Hong et al. in healthy Chinese adults using Sysme XT 2100 indeed confirmed variations of platelet indices between regions. The reported value of MPV for example ranged from 10.30 ± 0.80 to 12.36 ± 1.34 [21]. In another study by Maluf et al. a statistically significant difference in MPV, PDW, and P-LCR according to self-declared race/skin color was demonstrated, where mean MPV, PDW, and P-LCR values of white individuals were lower than those of individuals self-declared black or pardo (mixed skin color/brown) [22]. An earlier study by Barbara J to evaluate ethnic and sex differences in hematological profiles including platelet count and MPV reveled an MPV of 8.9 fl in Caucasians (eastern Europe), 9.1 fl in Afro-Caribbean’s and 9.4 fl in Sub-Saharan Africans (including few Ethiopians) [23]. It is evident that Africans have higher MPV as compared to the other groups. Though we have analyzed 42 healthy controls, the mean MPV was 10.3 fl which suggest that the actual size of the platelet in our study subjects could be higher.

The mean MPV of the healthy controls (10.3 fl) in the current study can identify ITP patients with 82 % sensitivity, 66 % specificity, 61.4 % positive predictive value and 85 % negative predictive value. In a similar study conducted by T. Numbenjapon et al. in healthy Thais, the mean MPV was 7.9 fl. This identified hyperdestructive thrombocytopenic patients with a sensitivity of 82.3 %, a specificity of 92.5 %, a PPV of 94.4 %, and a NPV of 77.1 % [6]. Kaito et al. analyzed the role of MPV, PDW and P-LCR in the diagnosis of ITP and reported somewhat an improved sensitivity and specificity where an MPV of >11 fl has a sensitivity of 87.2 % and a specificity of 80.0 % [7].

This variation in sensitivity, specificity and predictive values could be due to differences in the type of study participants, where some have compared only one patient group, bone marrow disease due to aplastic anemia against ITP [4, 7]. However, in our study more than 8 causes of bone marrow disease were identified. The other reason could be the predominance of chronic ITP which accounts 28 out of 33 ITP patients. These patients have relatively stable platelet count, on average 88 × 10⁹/L and a mean MPV of 11.6 fl with a range of 9.2 to 17. On the other hand hypoproductive patients have a mean MPV of 9.7 fl with arrange of 7.1 to 11.2; hence it is evident that some platelet indices values are overlapping between the two patient groups.

Supporting the above explanation in vitro studies showed that plasma auto antibodies from ITP patients not only are involved in platelet destruction, but may also contribute to the inhibition of platelet production by affecting megakaryocyte production and maturation [24, 25]. It suggests that a similar effect may occur in vivo. This may partly explain the lower platelet indices in our chronic ITP patients compared to the acute ITP cases. Despite hyper-destructive thrombocytopenia which is characterized by higher MPV, these chronic patients may have normal or even suppressed platelet production rate.

The significant negative correlation between the platelet count and the platelet indices in ITP patients seems to be mainly contributed by acute ITP patients who had a mean platelet count of 12.6x10⁹/L and mean MPV of 16.6 fl, PDW 19 fl and P-LCR of 51.5 %. This shows the platelet indices in particular MPV and P-LCR could have a better discriminating or prediction capacity for ITP where they are needed the most, during the early investigation and diagnosis of thrombocytopenic patients. Among the 33 ITP patients, 10 of them had bone marrow examination with result of no primary or secondary bone marrow disease. If not in all these 10 patients, the platelet indices could have assisted in predicting most patients to have ITP and could prevent them from undergoing this invasive procedure.

In conclusion these indices in particular MPV and P-LCR can discriminate ITP from hypoproductive thrombocytopenia and they may help in avoiding or delaying ITP patients from undergoing unnecessary, invasive bone marrow aspiration or prevent undesirable platelet transfusion. The mean platelet indices are relatively higher in our study groups. Therefore, cut off values need to be established on the given laboratory setup and place for the indices to be used as a discriminating tool for thrombocytopenia. Future studies comparing impedance and impedance with optical method and inclusion of more types of hyper-destructive thrombocytopenia may enable us to use these indices for broader patient groups.

ALL, acute lymphocytic leukemia; AML, acute myelocytic/myelogenous leukemia; BM, bone marrow; CBC, complete blood count; CLL, chronic lymphocytic leukemia; CML, chronic myolegenous leukemia; DIC, disseminated intravascular coagulation; EDTA, ethylene diamine tetra-acetic acid; fL, femto liter (10⁻¹⁵ litre); Hb, hemoglobin; HIV, human immunodeficiency virus; IPF, immature platelet fraction; IPU, information processing unit; ITP, immune thrombocytopenic purpura; IVIg, intravenous Immunoglobulin; MCH, mean cell hemoglobin; MCV, mean cell volume; MPV, mean platelet volume; NPV, negative predictive value; PCT, platecrit; PDW, platelet size distribution width; P-LCR, platelet large cell ratio; PPV, positive predictive value; RDW, red cell distribution width; RNA, ribonucleic acid; ROC, receiver operating curve; RP, reticulated platelets; TTP, thrombotic thrombocytopenic purpura