Objectives: Although guidelines recommend normalization of platelet counts as an appropriate endpoint for treatment in high-risk essential thrombocythemia (ET), retrospective studies could not prove a correlation of diagnostic platelet counts with an increased thrombotic rate. There is, however, an increasing evidence that leukocytosis is an important risk factor for arterial thrombosis in myeloproliferative neoplasms. Methods: This study considers the Austrian cohort of a European registry regarding the platelet-lowering therapeutic anagrelide. Influence of platelet and white blood cell (WBC) counts on thrombotic risk was assessed. Results: Using the calculated cutoffs of 574.5 G/L for platelets and 8.48 G/L for WBC counts, respectively, the Cox regression analysis revealed a clear influence of elevated platelets (P = 0.008) and WBC counts (P = 0.011) on the occurrence of major thrombotic events. The time to a major thrombotic event was shortest (P < 0.001) and the frequency related to 100 patient-years was highest (P = < 0.001) when both platelet and WBC counts ranged above the calculated cutoffs. Conclusion: Our data add evidence to the impact of platelet and WBC counts on thrombosis in ET. We suspect a particular interaction between platelets and WBC which might be based on a biological interplay depending on particular cell counts.