The effect of mycophenolate mofetil on platelet function

Abstract

Mycophenolate mofetil (MMF) raises platelet counts in patients with primary immune thrombocytopenia. However, studies indicate that MMF inhibits collagen-induced platelet aggregation, potentially increasing bleeding risk following MMF therapy. OBJECTIVE:The study evaluates the in vitro effect of MMF on platelet function. Blood samples (n=6) from healthy donors were incubated with vehicle, MMF or mycophenolic acid (MPA) at clinically relevant concentrations. Platelet aggregation was measured with flow cytometry and 96-well light transmission aggregometry (LTA). Using flow cytometry, we measured the expression of platelet glycoprotein receptors GPVI, CD49b, CD42b, CD42a, CD61 and CD41. Platelet activation was measured as the expression of P-selectin and the active form of the GPIIb/IIIa receptor following agonist stimulation. Agonists were: Adenosine diphosphate, thrombin receptor-activating peptide, collagen, collagen-related peptide and U46619. The Platelet Function Analyzer-200 was used to measure global platelet function RESULTS: MMF and MPA did not change platelet aggregation regardless of the agonist used. An exception was a significant, but minor decrease in platelet aggregation induced by a low collagen concentration. MMF (6±3%, p=0.02) and MPA (8±4%, p=0.01) compared with vehicle (22±11%). However, this was not observed 3 using the lesser sensitive LTA method. Compared with vehicle, MPA led to a significantly lower relative disposition of the surface collagen-receptor GPVI (7.8±1.8 versus 8.8±2.1 mean fluorescence intensity, p<0.001). In all other platelet related tests, neither MMF nor MPA showed any effect. CONCLUSION: MMF and MPA only had a minor effect on collagen-induced platelet aggregation, with MPA reducing the relative disposition of surface GPVI receptors.