Aspirin thrombosis

Vane, J. R. Botting, R M. The Mechanism of Action of Aspirin Thrombosis Research 2003, 110, 255-258. Moncada, S. Vane, J. R. Mode of Action of Aspirin-like Drugs Advances in Internal Medicine 1979, 24, 1-22. 

Aspirin has been remarkably successful in the treatment of the pain and swelling of inflammatory disease and in fact, an estimated 45,000 tons of aspirin are still consumed each year. This success resulted in the syntheses of many other aspirin-like drugs , now referred to as NSAIDs. Aspirin, however, continues to have a unique use in the prevention of thrombosis. Since it produces irreversible inhibition of COX-1 by acetylation of serine at position 530 in the active site, a daily low dose of aspirin will cause a cumulative inhibition of COX-1 in platelets, in the portal circulation. A gradual inhibition of platelet aggregation occurs, reducing the possibility of occlusion of coronary or cerebral vessels by platelet thrombi. However, there are no systemic... 

Roth GJ, Calverley DC Aspirin, platelets, and thrombosis theory and practice. Blood 1994 83 885. 

The ACCP Conference on Antithrombotic Therapy recommended against the use of aspirin as the primary method of VTE prophylaxis.2 Antiplatelet drugs clearly reduce the risk of coronary artery and cerebrovascular events in patients with arterial disease, but aspirin produces a very modest reduction in VTE following orthopedic surgeries of the lower extremities. The relative contribution of venous stasis in the pathogenesis of venous thrombosis compared with that of platelets in arterial thrombosis likely explains the reason for this difference. 

For patients undergoing primary PCI, clopidogrel is administered as a 300-to 600-mg loading dose followed by a 75 mg/day maintenance dose, in combination with aspirin 325 mg once daily, to prevent subacute stent thrombosis and long-term cardiovascular events. 

BP, blood pressure CBC, complete blood count DVT, deep vein thrombosis ECG, electrocardiogram ERDP/ASA, extended-release dipyridamole plus aspirin Hb, hemoglobin Hd, hematocrit ICP, intracranial pressure ICU, intensive care unit INR, international normalized ratio SAH, subarachnoid hemorrhage. 

One of the significant factors promoting late stent thrombosis has been found to be premature discontinuation of dual antiplatelet therapy (aspirin and clopidrogel). In an analysis of 4,666 of patients undergoing initial PCI with BMS or DES, researchers from the Duke Heart center reported that longterm risk for death and major cardiac events was significantly increased among patients in the DES... 

Unstable angina, non -wave MI Subcutaneous 120 international units/kg ql2h (maximum 10,000 international units/dose) given with aspirin until clinically stable. Prevention of deep vein thrombosis (DVT) or pulmonary edema in the acutely ill patient Subcutaneous 5000 international units once a day. 

The reported incidence of resistance to these drugs varies greatly, from less than 5% to 75%. In part this tremendous variation in incidence reflects the definition of resistance (recurrent thrombosis while on antiplatelet therapy vs in vitro testing), methods by which drug response is measured, and patient compliance. Several methods for testing aspirin and clopidogrel resistance in vitro are now FDA-approved however, their utility outside of clinical trials remains controversial. 

Aspirin decreases the incidence of transient ischemic attacks, unstable angina, coronary artery thrombosis with myocardial infarction, and thrombosis after coronary artery bypass grafting (see Chapter 34). 

ASPIRIN. [CAS 50-78-2]. A drug used for nearly a century to relieve headaches and geneial aches and pains and to leduce the swelling and pain associated with joints (gout, ague, rheumatoid arthritis). In recent years, attention to aspirin for its apparent role m reducing heart attacks (coronary thrombosis) and strokes has increased, Trial studies also are underway for its use in reducing the risk of fatal colon cancer. 

Finally, aspirin has also been used to prevent thrombus formation in peripheral veins (deep vein thrombosis [DVT]), and aspirin is sometimes used as an adjunct or alternative to anticoagulants (heparin, warfarin) that are routinely used to treat DVTs.8 Aspirin can likewise be administered to prevent thromboembolism following surgical procedures such as coronary artery bypass, arterial grafts, endarterectomy, and valve replacement 45,78 By preventing platelet-induced thrombogenesis, aspirin helps maintain patency and prevent reocclusion of vessels following these procedures. 

Dipyridamole (Persantine) is a vasodilator that, in combination with warfarin, inhibits embolization from prosthetic heart valves and, in combination with aspirin, reduces thrombosis in patients with thrombotic diseases. Dipyridamole by itself has little or no benefit in fact, in trials where a regimen of dipyridamole plus aspirin was compared with aspirin alone, dipyridamole provided no additional beneficial effect. Dipyridamole interferes with platelet function by increasing the cellular concentration of adenosine 3, 5 -monophosphate (cyclic AMP). This effect is mediated by inhibition of cyclic nucleotide phosphodiesterase and by blockade of uptake of adenosine, which acts at A2 receptors for adenosine to stimulate platelet adenylyl cyclase. The only current recommended use of dipyridamole is for primary prophylaxis of thromboemboli in patients with prosthetic heart valves the drug is given in combination with warfarin. 

Full-dose heparin therapy, beginning with an intravenous bolus of 10,000 U and continued for 4 to 24 h, is standard practice in patients undergoing angioplasty. Aspirin begun 1 d prior to surgery reduces periprocedural thrombosis and should be continued indefinitely due to its beneficial effect on coronary artery disease. 

In view of the perceived benefit of aspirin in the secondary prevention of stroke and myocardial infarction, two large trials involving physicians as subjects were initiated to study the effect of aspirin in the primary prevention of arterial thrombosis. In the American study, 22,000 volunteers (age 40 to 84 years) were randomly assigned to take 325 mg of aspirin every other day or placebo. The trial was halted early, after a mean follow-up of 5 years, when a 45% reduction in the incidence of myocardial infarction and a 72% reduction in the incidence of fatal myocardial infarction were noted with aspirin treatment. However, total mortality was reduced only 4% in the aspirin group, a difference that was not statistically significant, and there was a trend for a greater risk of hemorrhagic stroke with aspirin. Thus, the prophylactic use of aspirin in an apparently healthy population is not recommended at this time, unless there are risk factors for cardiovascular disease. 

As noted above, eicosanoids are involved in thrombosis because TXA2 promotes platelet aggregation and PGI2 inhibits it. Aspirin inhibits platelet COX to produce a mild clotting defect. 

Activation of platelets is considered an essential process for arterial thrombosis. Thus, treatment with platelet-inhibiting drugs such as aspirin and ticlopidine or clopidogrel is indicated in patients with transient ischemic attacks and strokes or unstable angina and acute myocardial infarction. In angina and infarction, these drugs are often used in conjunction with -blockers, calcium channel blockers, and fibrinolytic drugs. 

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