aspirin

Does Low-Dose Aspirin Therapy Complicate Oral Surgical Procedures?

Evan BlackwellJenna ChaAndrew Peterson

Learning Objectives

1. Be able to understand mechanism of COX 2. Be able to understand mechanism of NSAIDs3. Be able to state the effects & side effects of Aspirin4. Be able to reason your choice of action with Aspirin drug

holiday

Background• The fear of uncontrolled bleeding often prompts medical

practitioners to stop aspirin intake 7 to 10 days before any surgical procedure

• WHY?• The platelet lifespan is approximately 8 to 9 days

Learning objective 1: COX?

Learning objective 1: COX?

Learning objective 1: COX?

• COX-1 is also called as constitutive enzyme because it is produced by a cell under all types of physiological conditions. The amount at which constitutive enzymes are produced remain constant without regard of substrate concentration and physiological demand.

• On the other hand COX-2 is an inducible enzyme as it is produced under certain specific conditions like inflammation.

Learning objective 1: COX?

• PGs, mostly by COX-1, are constitutively expressed in almost

all tissues; COX-2 appears to be located in macrophages,

leukocytes and fibroblasts.

• Under normal physiologic conditions, PGs play an essential

homeostatic role in cytoprotection of gastric mucosa,

hemostasis, renal physiology, gestation, and parturition

• In platelets there is only COX-1exist (converts arachidonic acid

to TxA2)

• COX-1 predominant in gastric mucosa (source of cytoprotective

PGs)

• The production of PGs, (inducible COX-2 activity >> COX-1) at

sites of inflammation propagate pain, fever

Learning objective 1: COX?

• NSAIDs: Non-steroidal anti-inflammatory drugs• Usually used for treatment of acute or chronic conditions

for pain & inflammation• Aspirin, Ibuprofen, Naproxen, etc• Inhibits activity of both COX-1 and COX-2• COX-1 inhibition: can cause GI bleeding and ulcers• COX-2 inhibition: anti-inflammatory, analgesic and antipyretic

affects

Learning objective 2: Mechanism of NSAIDs

• Most NSAIDs – “nonselective COX inhibitors”• Inhibit both COX 1 & COX 2 • Inhibition is reversible

• Aspirin• Irreversible inhibition • Non-selective • Weakly more selective for COX-1

Learning objective 2: Mechanism of NSAIDs

• Possess a long channel (COX-2 channel is wider than in COX-1).• Non-selective NSAIDs enter channel (but not aspirin).• Block channels by binding with H-bonds to an arg half of the way

in.• This reversibly inhibits the COX by preventing arachidonic acid

from gaining access.• Selective COX-2 inhibitors generally more bulky molecules - can

enter and block the channel of COX-2, but not that of COX-1.

Learning objective 2: Mechanism of NSAIDs

• 2-(acetyloxy)benzoic acid• Aspirin, the only NSAID able to irreversibly inhibit COX• Indicated for inhibition of platelet aggregation• By inhibiting action of Thromboxane A2

• Used for:• Management of arterial thrombosis• Prevention of adverse cardiovascular disease

• Salicylate • Aspirin acetylates COX (at ser530) and is, therefore,

irreversible.• Acetyl group is covalently attached to serine residue in the

active site of the COX enzyme.

Learning objective 3: Aspirin

Learning objective 3: Aspirin

• Analgesic (0.3-0.6 g/day): PG• Refers to the relief of pain by a mechanism other than the reduction

of inflammation (for example, headache); produce a mild degree of analgesia which is much less than the analgesia produced by opioid analgesics such as morphine

• Anti-inflammatory (3-5 g/day): PG• These drugs are used to treat inflammatory diseases and injuries,

and with larger doses - rheumatoid disorders

• Antipyretic (0.3-0.6 g/day): PG• Reduce fever; lower elevated body temperature by their action on

the hypothalamus; normal body temperature is not reduced

• Antiplatelet (30-100 mg/day): Thromboxane• Inhibit platelet aggregation, prolong bleeding time; have

anticoagulant effects

Learning objective 3: Aspirin effects

• Gastrointestinal symptoms

• CNS toxicity

• Allergic reaction (urticaria, angioneurotic edema, aspirin asthma, occasionally anaphylactic shock)

• Salicylate reaction (CNS reaction)

• Renal damage

• Hematologic effects

• Metabolic acidosis stimulates medullary respiratory center respiratory alkalosis

Learning objective 3: Aspirin Side effects

Risks• Interruption of aspirin therapy may expose these patients

to the risk of developing thromboembolism, myocardial infarction or cerebrovascular accident

Purpose of the study• This study was initiated to measure the effect of low-dose

aspirin therapy on intraoperative and postoperative bleeding in patients undergoing oral surgery.

• In addition, the authors compared the relationship between clinical hemorrhagic complications and the tested bleeding time

Low Dose Aspirin Regimens• Continuous low-dose aspirin regimens have become

popular in the last decease for treating cardiovascular and peripheral vascular diseases, patients are reluctant to stop their regular therapy before undergoing surgical procedures

Fuster et al. Prog Cardiovasc Dis 1987

Materials and Methods• The study group was composed of 39 patients• Mean age: 62 +/- 13.2 years• Age Range: 39 to 89 years• 15 women/24 men

• All patients were receiving 100 mg of aspirin per day on a long-term basis as a secondary preventive drug for cardiovascular or peripheral vascular diseases

M & M continued• Patients were randomly divided into an experimental group

and a control group• Patients in the control group continued aspirin therapy • Patients in the experimental group stopped aspirin therapy

seven days before their extraction and did not resume until the day after the procedure

Bleeding time• Bleeding time is a medical test done on someone to assess

their platelets function. It involves making a patient bleed then timing how long it takes for them to stop bleeding

• Bleeding normally stops within 1 to 9 minutes.• ** However, values may vary from lab to lab.

M & M• Surgical procedures were divided into three categories• Simple extractions• Compound procedures• Complex procedures

• Before all procedures, patients received only local anesthetic (3% mepivacaine)

Intraoperative bleeding time• Measured by subtracting the volume of irrigation fluid from

the volume of blood accumulated in the suction trap

Results• Discontinued aspirin therapy • 1.8 +/- 0.47 minutes

• Continued aspirin therapy • 3.1 +/- 0.65 minutes

• P value = 0.004• Statistically significant

• But both groups were still within the normal bleeding time range of 1 to 4.5 minutes

Results continued

• In 33 of the 39 patients, intraoperative bleeding was controlled with suturing, and local hemostasis with direct packing of gauze

• 6 patients received 10% tranexamic acid, an antifibrolytic agent that stabilizes the blood clot by inhibiting plasmin, was added to the local packing

• No episodes of uncontrolled bleeding reported during the week after surgery

Discussion• Until the early 1980’s, aspirin was used as an anti-

inflammatory, analgesic, and antipyretic drug for a short period of time

• Major side affects, mainly, gastrointestinal irritation and ulcers

Controversy • With the increase use of low-dose aspirin, this has

presented dentists with the dilemma of whether to advise patients to discontinue aspirin therapy prior to surgical procedures.

• Controversy currently exists in the literature

Conclusion• In contrast to other studies which involved high dose

aspirin therapy, their study was a prospective study that examined the bleeding tendency of patients receiving regular low dose aspirin therapy.

• They suggest there is no need to expose patients to the risk thromboembolism, cerebrovascular accident or myocardial infraction undergoing dental extractions

Bottom Line• Patients should continue with low-dose aspirin therapy

prior to dental extractions during the preoperative phase