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Published on: December 27, 2017
Influence of mycophenolic acid and FK-506 on human platelet activation in vitro
1Department of Nephrology and Rheumatology, Heinrich Heine University, Düsseldorf, Germany. kleinrm@uni-duesseldorf.de
Background/Aim:
FK-506 (FK) and mycophenolic acid (MPA) are immunosuppressive agents used in kidney transplant recipients. Their effect on posttransplant thromboembolic complications is either controversial (FK) or has not been described (MPA). Thromboembolic events are among the consequences of platelet hyperaggregability which can be identified by measuring platelet aggregation. The aim of this study was to evaluate the in vitro effects of MPA and FK upon platelet activation in healthy subjects.
Methods:
Platelet-rich plasma from healthy volunteers (n = 18) was incubated with FK (70 ng/ml), FK vehicle, and MPA (30 microg/ml) before platelet aggregation was induced by the platelet agonists adenosine diphosphate (2 and 5 microM) and collagen 0.5 and 1.0 microg/ml). Aggregation was measured by recording the optical density.
Results:
MPA resulted in a significant decrease in the platelet response to collagen (1.0 microg/ml) in platelet-rich plasma, whereas FK significantly increased platelet aggregation in response to collagen (0.5 microg/ml). The vehicle of FK had no influence on platelet aggregation with either agonist.
Conclusions:
The decreased platelet-activating response following preincubation with MPA may favor its use in kidney transplant recipients to reduce thromboembolic events. The FK-induced enhancement of platelet aggregation shown in vitro may lead to thromboembolic complications in transplant recipients.
Insights
Mycophenolic acid (MPA) decreased platelet aggregation, potentially reducing thromboembolic events in kidney transplant recipients. However, FK-506 (FK) increased platelet aggregation in vitro, possibly increasing complication risks.
Area of Science:
- Immunopharmacology
- Transplantation Medicine
- Hematology
Background:
- Immunosuppressive agents FK-506 (FK) and mycophenolic acid (MPA) are crucial for kidney transplant recipients.
- The impact of FK and MPA on posttransplant thromboembolic complications remains unclear.
- Platelet hyperaggregability, assessed by platelet aggregation, is linked to thromboembolic events.
Purpose of the Study:
- To investigate the in vitro effects of MPA and FK on platelet activation in healthy subjects.
- To assess the potential of MPA and FK to influence platelet aggregation relevant to transplant complications.
Main Methods:
- Platelet-rich plasma from 18 healthy volunteers was used.
- Incubation with MPA (30 microg/ml) and FK (70 ng/ml) or FK vehicle.
- Platelet aggregation induced by adenosine diphosphate and collagen, measured via optical density.
Main Results:
- MPA significantly reduced platelet response to collagen (1.0 microg/ml).
- FK significantly increased platelet aggregation in response to collagen (0.5 microg/ml).
- FK vehicle had no effect on platelet aggregation.
Conclusions:
- MPA's anti-aggregatory effect may reduce thromboembolic events in kidney transplant recipients.
- FK's pro-aggregatory effect in vitro suggests a potential risk for thromboembolic complications.
- Further clinical studies are warranted to confirm these in vitro findings.
