Sepsis severity is the major determinant of circulating thrombopoietin levels in septic patients.

Objective: To measure serum thrombopoietin levels and to investigate their relationship with platelet counts and other potential determinants in septic patients.

Design: Prospective study comparing septic patients and healthy volunteers.

Setting: General intensive care units in two tertiary university hospitals.

Patients: A total of 152 consecutive septic patients (69 with sepsis, 24 with severe sepsis, and 59 with septic shock). Twenty-two healthy volunteers served as control subjects. Sepsis severity was determined by grading septic patients in those having sepsis, severe sepsis, and septic shock.

Interventions: None.

Measurements And Main Results: After blood sampling, platelet counts, and serum thrombopoietin, interleukin-6 and C-reactive protein levels were measured. Platelets did not decrease in patients with sepsis, but they significantly decreased in patients with severe sepsis and septic shock (p <.01 vs. controls and sepsis). In contrast, thrombopoietin levels (median [range]) increased in patients with sepsis (159 [34-1272] pg/mL) compared with controls (57 [33-333] pg/mL, p <.001), exhibiting further significant increase in patients with severe sepsis and septic shock (461 [73-1550] and 522 [45-2313] pg/mL, respectively, p <.001 vs. sepsis). In multiple regression analysis, thrombopoietin levels were independently related only to sepsis severity (higher in patients with increased sepsis severity, p <.001) and platelet counts (higher in patients with lower platelet counts, p =.004). Sepsis severity accounted for most of the variance explained by the model. Thrombopoietin was significantly related to interleukin-6 (r =.26) and C-reactive protein (r =.37, p <.001 for both). In serial measurements, interleukin-6 peak values constantly preceded those of thrombopoietin, whereas peaks in thrombopoietin levels coincided with clinical episodes of septic shock.

Conclusions: Sepsis severity is the major determinant of elevated thrombopoietin levels in septic patients, whereas platelet count is a secondary determinant. Thrombopoietin represents a potential marker of sepsis severity.