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

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.