Abstract
Essential thrombocytosis (ET) is a myeloproliferative disorder whose main complication is thrombothic events. Reduction of platelet count is associated with a decrease in the risk for thrombosis. Recently it was shown that although anagrelide and hydroxyurea lower platelet counts to the same extent, hydroxyurea decreased the rate of arterial thrombosis and increased the rate of venous thrombosis compared to anagrelide. The reason for the different effects is unknown. The endothelium has important antithrombotic properties. Therefore, we hypothesized that hydroxyurea and anagrelide may have different effects on endothelial function in patients with ET.
Thirty patients with ET were studied; 12 treated with anagrelide and 18 with hydroxyurea. Endothelial function was assessed using a semi-automated pulse wave analysis system (SphygmoCor PVX, AtCor Medical, Sydney Australia). Pulse wave is recorded at the radial artery. Using a validated transfer function, the following variables are determined:
central systolic blood pressure (CSBP); augmentation index (AIx), a reflection of arterial stiffness; augmentation index adjusted for heart rate (AIx@75).
Measurements were taken at baseline, after inhalation of terbutaline 500 mcg (representing endothelial dependent vasodilation due to NO synthesis), and after sublingual nitroglycerine 400 mcg (representing endothelial independent vasodilation). The difference between baseline AIx and maximum response after terbutaline and nitroglycerine are given as EDV (endothelial dependent vasodilation) and EIV (endothelial independent vasodilation), respectively.
There was no difference between the two groups of patients with regard to disease duration, age, gender, prior thrombotic events and risk factors for atherosclerosis including BMI, hyperlipidemia, diabetes mellitus, smoking history and hypertension. Mean Hct and platelet count was the same in both groups of patients. However, WBC and neutrophil counts were lower in patients treated with hydroxyurea compared to the patients treated with anagrelide (WBC 6.2±1.4 K/μl vs. 8.4±3.4 K/μl, p=0.07, neutrophils 4.0±1.2 K/μl vs. 6.3±2.9 K/μl, p=0.05). Parameters of arterial stiffness and endothelial function did not differ significantly between the two groups of patients (Table 1). There was no correlation between platelet count and endothelial function, however a correlation between CSBP and age was found (R= 0.615 p<0.001).
In conclusion: our preliminary results do not support a different effect for hydroxyurea and anagrelide on arterial stiffness and endothelial function in patients with ET. In accordance with previous reports we found a lower neutrophil count in the group of patients on hydroxyurea therapy. This may affect the interaction between neutrophils and the vessel wall thereby decreasing the rate of arterial thrombosis.
Table 1 Therapy (N) Anagrelide (12) Hydroxyurea (18) CSBP mmHg 120±14 122±21 AIx % 26±12 33±11 AIx@75 % 25±10 27±10 EDV % −2±8.6 0.6±7.5 EIV % −11±9 −15±7
Pulse Wave Analysis by Applanation Tonometry for the Measurement of Arterial Stiffness