What medications can cause increased bruising?

Medications That Cause Increased Bruising

Antiplatelet agents (aspirin, clopidogrel, prasugrel, ticagrelor), anticoagulants (warfarin, heparins, DOACs), NSAIDs, SSRIs, certain antibiotics, and corticosteroids are the primary medications that cause increased bruising through various mechanisms affecting hemostasis.

Antiplatelet Agents

These medications are the most common cause of drug-induced bruising and bleeding complications:

P2Y12 Inhibitors

• Clopidogrel causes high rates of excessive skin bruising, particularly when combined with aspirin 1
• Clopidogrel increases bleeding risk for the lifetime of the platelet (7-10 days) due to irreversible platelet inhibition 2
• Prasugrel carries increased bleeding risk, especially in patients weighing <60 kg, age ≥75 years, or with concomitant medications that increase bleeding risk 1
• Ticagrelor similarly increases bruising and bleeding risk when used with aspirin 1

Aspirin and NSAIDs

• Aspirin and NSAIDs increase bleeding risk by inhibiting platelet function and causing gastric erosions 1
• High-dose aspirin (>1.5 g/day) significantly augments bleeding complications 1
• Chronic NSAID use compounds bleeding risk when combined with anticoagulants 1, 2
• These agents are among the most important causes of drug-induced platelet dysfunction in clinical practice 3

Glycoprotein IIb/IIIa Inhibitors

• Abciximab, eptifibatide, and tirofiban cause bleeding through potent platelet aggregation inhibition 1

Anticoagulants

All anticoagulants carry significant bleeding and bruising risk through direct effects on the coagulation cascade:

Warfarin

• Warfarin increases bleeding risk through impaired synthesis of vitamin K-dependent coagulation factors 1
• Concomitant aspirin use with warfarin significantly increases bleeding risk (5.6% vs 1.4% with warfarin alone) 4
• Multiple drug interactions potentiate warfarin's effect, including antibiotics (trimethoprim-sulfamethoxazole, ciprofloxacin, metronidazole, fluconazole), chemotherapy agents (fluoropyrimidines), and acetaminophen >2g daily 1

Direct Oral Anticoagulants (DOACs)

• Dabigatran, rivaroxaban, apixaban, and edoxaban all cause increased bruising and bleeding 1, 5
• The number of drug-drug interactions with DOACs significantly increases bleeding events independent of comorbidities 6
• Common DDI drugs include NSAIDs, antiplatelet agents, diltiazem, and amiodarone 6

Heparins

• Unfractionated heparin and low-molecular-weight heparins (enoxaparin, dalteparin) increase bleeding risk 1
• Heparin bridging therapy increases bleeding complications (7.0%) compared to continued warfarin (3.7%) or discontinued warfarin (2.1%) 4

Other Medications

Selective Serotonin Reuptake Inhibitors (SSRIs)

• SSRIs impair platelet function and increase bleeding risk, including epistaxis and bruising 3, 5

Antibiotics

• Certain antibiotics (particularly high-dose penicillins and moxalactam) inhibit platelet function 1
• Second- and third-generation cephalosporins inhibit vitamin K cycling, augmenting anticoagulant effects 1

Cardiovascular Medications

• Diltiazem and verapamil increase DOAC plasma concentrations through P-glycoprotein inhibition 1
• Amiodarone moderately inhibits CYP2C9, increasing warfarin levels and necessitating average 25% dose reduction 1
• Dronedarone strongly inhibits P-glycoprotein and should generally be avoided with DOACs 1

Intranasal Corticosteroids

• These agents are associated with epistaxis and increased bruising tendency 5

Volume Expanders

• Certain volume expanders can impair platelet function 3

Critical Drug Combinations

The following combinations carry particularly high bleeding and bruising risk:

• Triple therapy (anticoagulant + dual antiplatelet therapy) significantly increases bleeding complications 1
• Warfarin plus aspirin increases bleeding from 1.4% to 2.8% in valve patients 1
• Clopidogrel plus aspirin shows high rates of excessive skin bruising 1
• Major bleeding occurs in children receiving clopidogrel with concomitant warfarin 1

Clinical Implications

• Patients with preexisting hemostatic defects are at highest risk for bleeding complications when exposed to these medications 3
• Bruising and bleeding risk persists for 5-10 days after discontinuation of antiplatelet agents due to irreversible platelet inhibition 2
• Cancer patients have 2.2-fold higher risk of major bleeding (12.4% vs 4.9%) during anticoagulation compared to non-cancer patients 1