Does diflusinal (nonsteroidal anti-inflammatory drug (NSAID)) inhibit platelet function?

Does Diflunisal Inhibit Platelets?

Yes, diflunisal does inhibit platelet function, but its antiplatelet effect is substantially weaker and more transient compared to aspirin, with clinically relevant inhibition occurring only at higher doses (≥500-1000 mg twice daily). 1, 2

Mechanism and Pharmacologic Properties

Diflunisal is a nonsteroidal anti-inflammatory drug (NSAID) that reversibly inhibits the COX-1 enzyme, thereby reducing thromboxane A2 (TXA2) production in platelets. 1 Unlike aspirin, which permanently acetylates COX-1, diflunisal's antiplatelet effects are:

• Reversible and dose-dependent, lasting only while the drug maintains therapeutic serum levels 2, 3
• Short-lived, with a half-life of 7-15 hours and antiplatelet effects returning to baseline within 24 hours after discontinuation 1, 2
• Quantitatively weaker than aspirin at comparable doses 2, 3

Dose-Dependent Platelet Effects

The degree of platelet inhibition varies significantly with diflunisal dosing 2:

• 250 mg twice daily: No measurable effect on platelet function 2
• 500 mg twice daily: Minimal inhibition of collagen-induced platelet serotonin release 2
• 1000 mg twice daily: Moderate inhibition of platelet malondialdehyde production, modest prolongation of bleeding time (not statistically significant), and increased fecal blood loss (P<0.05) 2

In contrast, aspirin 650 mg twice daily produces marked inhibition of platelet aggregation with effects lasting up to 5 days after discontinuation. 2

Clinical Implications for Perioperative Management

For surgical planning, diflunisal requires significantly less interruption time than irreversible platelet inhibitors. 1 The American College of Chest Physicians guidelines classify diflunisal among NSAIDs with a 7-15 hour half-life, meaning restoration of platelet function occurs within 1-2 days of discontinuation rather than the 7-10 days required for aspirin or clopidogrel. 1

Bleeding Risk Profile

The FDA drug label notes that NSAIDs including diflunisal "inhibit platelet aggregation and have been shown to prolong bleeding time in some patients," but emphasizes that "unlike aspirin, their effect on platelet function is quantitatively less, of shorter duration, and reversible." 4

Clinical studies demonstrate 2, 5:

• Diflunisal at therapeutic doses (up to 500 mg twice daily) does not significantly alter bleeding time or cause clinically meaningful gastrointestinal blood loss 5
• Only at the highest dose (1000 mg twice daily) does diflunisal modestly increase fecal blood loss 2
• Spontaneous bleeding complications outside the GI tract are extremely rare in hemostatically normal individuals 3

Important Caveats

Patients at increased bleeding risk require careful monitoring when taking diflunisal, including those with 4, 3:

• Coagulation disorders or inherited platelet dysfunction
• Concurrent anticoagulant therapy
• Planned surgery where optimal hemostasis is critical (neurosurgery, ophthalmologic procedures, genitourinary or oral cavity manipulation)
• Concurrent alcohol use

Diflunisal should not be considered a substitute for aspirin in cardiovascular prophylaxis, as its antiplatelet effect is too weak and transient for thromboembolic disease prevention. 2, 6

Drug Interactions

Unlike ibuprofen, diflunisal does not appear to antagonize aspirin's irreversible platelet inhibition when co-administered. 6 Studies show that diflunisal at steady-state plasma concentrations of approximately 0.35 mmol/L does not impair the anti-aggregatory effect of aspirin test doses. 6