ABSTRACT
Title
Aspirin resistance in patients with myeloproliferative neoplasms
Authors
Candeo N, Vettore S, Tezza F, Bertozzi I, Randi ML
Dept of Medical and Surgical Sciences, University of Padova, Padova, Italy
Dept of Medical and Surgical Sciences, University of Padova, Padova, Italy
Abstract
BACKGROUND
Low-dose aspirin (100mg/die) improves the survival of patients with cardiovascular events; however, about 25% of the patients treated with aspirin present thromboembolic complications (aspirin resistance). Pharmacological resistance is defined as the inability of aspirin to inhibit platelet aggregation and thromboxane production.
Patients affected by myeloproliferative neoplasms (MPN) are at risk for thromboembolic complications and low-dose aspirin are effective also in these patients in reducing their thromboembolic risk. At present, few is known about aspirin resistance in this set of patients.
This study explores pharmacological aspirin resistance in patients with MPN, in particular with polycythemia vera (PV) and essential thrombocythemia (ET), evaluated with platelet aggregation and serum thromboxane (TxB2) assay.
PATIENTS AND METHODS
We studied 123 MPN patients (41 PV and 82 ET), 83 were treated with aspirin (100mg/die) (MPN-ASA) and 40 were not (MPN-basal). PV and ET were diagnosed in agreement with WHO criteria. As controls we studied 50 patients treated with aspirin (100mg/die) for secondary prevention of thrombosis (Controls-ASA) and 42 healthy subjects (Controls). Platelet aggregation under 1 mM arachidonic acid (AA) stimulus was evaluated with Born’s method. Serum thromboxane B2 (TxB2) was measured with ELISA assay (Thromboxane B2 Express EIA kit-monoclonal, Cayman Chemical Company; USA). Comparison between categorical variables was performed by χ2test and the threshold of serum TxB2 has been defined with ROC curve considering Controls and Controls-ASA TxB2 levels and obtaining a cut-off value of TxB2 to define the “aspirin resistance”.
RESULTS
All Controls-ASA (100%) had suppressed AA-aggregation (<10%), while 22 MPN-ASA (26.5%) had not (80 ± 16%). No statistical difference was found in serum TxB2 between Controls and MPN basal or between the MPN-ASA and Controls-ASA. TxB2 production was significantly reduced in Controls-ASA compared to Controls (p <0.0001) as well as in MPN-ASA compared to MPN-basal (p = 0.04); however, MPN-ASA had significantly higher levels of TxB2 than Controls-ASA (p <0.0001).
Serum TxB2 948 pg/plts x 10-8 was the cut-off limit to distinguish patients with a reduced suppression of TxB2 by aspirin (aspirin resistant). None of Controls and MPN-basal had a TxB2 value lower than 948 pg/plts x 10-8, while 2 (9.5%) Controls-ASA and 37 MPN-ASA (48%) were “aspirin resistant”. 18 MPN-ASA (25%) had both an AA-aggregation > 10% pattern and a reduced suppression of serum TxB2 production, despite the use of aspirin.
CONCLUSIONS
Pharmacological aspirin resistance occurs more frequently in MPN patients than in general population. Platelet aggregation can identify aspirin resistance in about 25% of MPN patients while an incomplete inhibition of serum TxB2 identify aspirin resistance in about 50% of MPN patients.
Low-dose aspirin (100mg/die) improves the survival of patients with cardiovascular events; however, about 25% of the patients treated with aspirin present thromboembolic complications (aspirin resistance). Pharmacological resistance is defined as the inability of aspirin to inhibit platelet aggregation and thromboxane production.
Patients affected by myeloproliferative neoplasms (MPN) are at risk for thromboembolic complications and low-dose aspirin are effective also in these patients in reducing their thromboembolic risk. At present, few is known about aspirin resistance in this set of patients.
This study explores pharmacological aspirin resistance in patients with MPN, in particular with polycythemia vera (PV) and essential thrombocythemia (ET), evaluated with platelet aggregation and serum thromboxane (TxB2) assay.
PATIENTS AND METHODS
We studied 123 MPN patients (41 PV and 82 ET), 83 were treated with aspirin (100mg/die) (MPN-ASA) and 40 were not (MPN-basal). PV and ET were diagnosed in agreement with WHO criteria. As controls we studied 50 patients treated with aspirin (100mg/die) for secondary prevention of thrombosis (Controls-ASA) and 42 healthy subjects (Controls). Platelet aggregation under 1 mM arachidonic acid (AA) stimulus was evaluated with Born’s method. Serum thromboxane B2 (TxB2) was measured with ELISA assay (Thromboxane B2 Express EIA kit-monoclonal, Cayman Chemical Company; USA). Comparison between categorical variables was performed by χ2test and the threshold of serum TxB2 has been defined with ROC curve considering Controls and Controls-ASA TxB2 levels and obtaining a cut-off value of TxB2 to define the “aspirin resistance”.
RESULTS
All Controls-ASA (100%) had suppressed AA-aggregation (<10%), while 22 MPN-ASA (26.5%) had not (80 ± 16%). No statistical difference was found in serum TxB2 between Controls and MPN basal or between the MPN-ASA and Controls-ASA. TxB2 production was significantly reduced in Controls-ASA compared to Controls (p <0.0001) as well as in MPN-ASA compared to MPN-basal (p = 0.04); however, MPN-ASA had significantly higher levels of TxB2 than Controls-ASA (p <0.0001).
| Platelets x109/L | TxB2 pg/ml | TxB2 pg x 10-8plts | |
| Controls (42) | 229±73 | 36451±5754 | 25085±6788 |
| MPN basal (22) | 584 ±120 | 45058±32515 | 32099±6650 |
| Controls-ASA (21) | 236± 90 | 1095±170 | 441±65 |
| MPN- ASA (77) | 614±323 | 5759±2881 | 1432±194 |
Serum TxB2 948 pg/plts x 10-8 was the cut-off limit to distinguish patients with a reduced suppression of TxB2 by aspirin (aspirin resistant). None of Controls and MPN-basal had a TxB2 value lower than 948 pg/plts x 10-8, while 2 (9.5%) Controls-ASA and 37 MPN-ASA (48%) were “aspirin resistant”. 18 MPN-ASA (25%) had both an AA-aggregation > 10% pattern and a reduced suppression of serum TxB2 production, despite the use of aspirin.
CONCLUSIONS
Pharmacological aspirin resistance occurs more frequently in MPN patients than in general population. Platelet aggregation can identify aspirin resistance in about 25% of MPN patients while an incomplete inhibition of serum TxB2 identify aspirin resistance in about 50% of MPN patients.