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Turbidimetry on Human Washed Platelets: The Effect of the Pannexin1-inhibitor Brilliant Blue FCF on Collagen-induced Aggregation
Published on: April 6, 2017
Plasma from rheumatoid patients taking low dose methotrexate enhances platelet aggregation
S A Saeed1, A H Gilani, H Rasheed
1Department of Biological and Biomedical Sciences, The Aga Khan University, Karachi, Pakistan. arshad.saeed@aku.edu
Abstract:
Methotrexate (MTX) in low doses is commonly used to treat rheumatoid arthritis (RA). At least 36 deaths have been attributed to bone marrow cytotoxicity associated with low dose MTX. The goal was to determine if plasma from arthritis patients taking low dose MTX induces platelet aggregation in platelet rich plasma from healthy volunteers. Plasma from patients on MTX alone caused a 3-fold increase in aggregation vs plasma from controls (P<0.05). Plasma from patients not taking MTX or taking MTX with diclofenac caused aggregation to a lesser extent. Diclofenac, along with several others NSAIDs and cyclooxygenase inhibitors, depressed aggregation produced by arachidonic acid in platelet rich plasma from healthy volunteers. A precise mechanism for amplification of aggregation by MTX plasma and its relationship to MTX toxicity remains unknown. However, a serum factor may be produced by MTX that modulates the activity of cyclooxygenase, thereby influencing aggregation.
Insights
Low-dose methotrexate (MTX) for rheumatoid arthritis (RA) patients significantly increases platelet aggregation. This effect may be linked to MTX-induced serum factors impacting cyclooxygenase activity and contributing to toxicity.
Area of Science:
- Rheumatology
- Hematology
- Pharmacology
Background:
- Low-dose methotrexate (MTX) is a standard treatment for rheumatoid arthritis (RA).
- MTX has been associated with serious adverse effects, including bone marrow cytotoxicity, with at least 36 deaths reported.
- The precise mechanisms underlying MTX toxicity remain incompletely understood.
Purpose of the Study:
- To investigate whether plasma from RA patients treated with low-dose MTX induces platelet aggregation.
- To compare the effects of MTX alone versus MTX in combination with diclofenac on platelet aggregation.
- To assess the impact of NSAIDs and cyclooxygenase inhibitors on platelet aggregation.
Main Methods:
- Platelet-rich plasma from healthy volunteers was used.
- Plasma samples were collected from rheumatoid arthritis patients on MTX therapy and from control subjects.
- Platelet aggregation was measured in response to patient or control plasma and to arachidonic acid.
Main Results:
- Plasma from patients on MTX alone induced a significant 3-fold increase in platelet aggregation compared to controls (P<0.05).
- Plasma from patients not on MTX or on MTX with diclofenac showed a lesser degree of platelet aggregation.
- Diclofenac and other NSAIDs/cyclooxygenase inhibitors inhibited arachidonic acid-induced platelet aggregation.
Conclusions:
- Low-dose methotrexate treatment in RA patients is associated with enhanced platelet aggregation.
- A potential MTX-induced serum factor may modulate cyclooxygenase activity, influencing platelet aggregation.
- Further research is needed to elucidate the exact mechanism linking MTX-induced platelet aggregation to its toxicity.
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