High levels of thrombopoietin in sera of patients with essential thrombocythemia: Cause or consequence of abnormal platelet production?

Thrombopoietin (TPO) is the most important regulator of megakaryocyte devel opment and platelet production. Platelet production is thought to be regula ted by a negative regulatory feed back loop. In an attempt to evaluate the role of TPO in the pathobiology of essential thrombocythemia (ET), we have examined levels of TPO and other cytokines with thrombopoietic activity (in terleukin-6 and interleukin-11) in sera obtained from 25 patients with ET ( ten treated, 15 untreated) and 117 healthy control subjects. TPO serum leve ls were assessed using a sandwich-antibody ELISA that utilizes a polyclonal rabbit antiserum for both capture and signal. The mean serum TPO level in 25 ET patients was significantly elevated (545 +/- 853 pg/ml) as compared w ith that in healthy con trols (95.3 +/- 54.0 pg/ml, p < 0.001). The differe nce in TPO serum levels between ten treated (781 +/- 1229 pg/ml) and 15 unt reated ET patients (355 +/- 458 pg/ml) did not reach statistical significan ce (p = 0.09). We conclude that either consumption or production of TPO is altered in ET. Failure of appropriate feedback regulation and continued meg akaryocyte stimulation by an elevated TPO may play an important role in the pathobiology of ET.