Indirect study of thrombopoiesis(TPO, reticulated platelets, glycocalicin)in patients with hereditary macrothrombocytopenia

Abstract

Chronic isolated hereditary macrothrombocytopenia (CHMT) is a congenital form of macrothrombocytopenia that seems to be due to defective production secondary to a disturbance in megakaryocyte fragmentation. To better understand the pathogenesis of thrombopoiesis in this hereditary thrombocytopenic disorder, we determined the percentage of reticulated platelets (RP), plasma glycocalicin (GC) and thrombopoietin (TPO) levels in 29 patients with CHMT, 23 patients with immune thrombocytopenic purpura (ITP), and 17 patients with thrombocytopenia secondary to decreased bone marrow megakaryocytes (hypoplasia). The % RP was similar in CHMT (2.27 +/- 1.33) and hypoplasia (1.98 +/- 1.35) patients and markedly lower than that in ITP patients (8.80 +/- 7.97; p <0.001), suggesting that the production of new platelets is reduced in CHMT. Plasma GC was within the normal range (0.84 +/- 0.16 microg/mL) both in patients with CHMT (0.63 +/- 0.20 microg/mL) and ITP (0.82 +/- 0.90 microg/mL), while it was significantly decreased in patients with hypoplasia (0.16 +/- 0.04 microg/mL; p < 0.001). When the GC value was normalized for platelet count, the GC index was normal in CHMT patients (2.05 +/- 1.1) and in patients with hypoplasia (0.85 +/- 0.10) while it was significantly increased in ITP patients (10.88 +/- 18.00; p<0.001); thus, patients with CHMT seem to have a normal platelet turnover. TPO was significantly increased in CHMT (195 +/- 72 pg/ml) as compared with normal (80 +/- 53 pg/ml; p < 0.002); however, the mean level was not as high as in ITP patients (345 +/- 167 pg/mL; p < 0.001). This finding suggests that CHMT syndrome is not secondary to a defective production of TPO and that megakaryocyte mass is nearly normal.

Evaluation of the immature platelet fraction contribute to the differential diagnosis of hereditary, immune and other acquired thrombocytopenias

“…This was first assessed in 2000 in HM, in a study with 29 patients with chronic hereditary thrombocytopenia and 23 patients with ITP. Using a flow cytometry-based method, markedly lower reticulated platelet counts were observed in patients with HM compared to ITP 13 . More recently, the IPF% was evaluated in a group of 15 patients with congenital macrothrombocytopenia using an automated hematological analyzer as in our study.…”

“…In 2000, Fabris et al . evaluated reticulated platelets by flow cytometry in a population of 29 patients with HM, observing reduced IPF values when compared to ITP 13 . More recently, Miyazaki et al .…”

Reticulated platelets: analytical aspects and clinical utility

“…Kienast and Schmitz initiated a breakthrough in the field when they described a flow cytometric technique for analyzing retPLT, based on RNA staining by thiazole orange [15]. In subsequent years, several research groups published their findings in a wide variety of conditions like thrombocytopenia [16][17][18][19][20][21], thrombocytosis [22,23], after stem cell transplantation [24][25][26][27], hereditary platelet diseases [28,29], thrombo-embolic disorders [30,31], kidney disease [32][33][34], preeclampsia [35], hyperthyroidism [36] and in healthy and thrombocytopenic neonates [37,38]. The overall conclusion from these studies is that retPLT in blood represent a useful non-invasive marker of megakaryopoietic activity in the bone marrow.…”

Effects of Sepsis on Neonatal Thrombopoiesis

“…Forty-two nonthrombocytopenic neonates were studied to establish the normal concentration of CMPs. The mean GA of these infants was 31 Ϯ 5 wk (range [25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41] and their mean postconceptional age (PCA, gestational age ϩ weeks of life) was 33 Ϯ 4.8 wk (range [25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42]. The mean CMP concentration was 99.5 Ϯ 13.6 (16).…”

“…This panel of tests was also chosen based on a number of previous studies in children and adults, which demonstrated that the use of several tests in combination was better at differentiating disorders of production from disorders of consumption than any single test (20,26,27). Specific mechanisms of thrombocytopenia that have been identified applying some or all of these tests, and the interpretation of different patterns, are summarized in Table 1.…”