aspirin resistance

بسم الله الرحمن الرحيم : 

بسم الله الرحمن الرحيم وقل رب زدني علما صدق الله العظيم

Aspirin Resistance : 

Aspirin Resistance By A.Abdellatif.A.Syliman Internal Medicine department Qena University Hospital

What is aspirin? : 

What is aspirin? Aspirin belongs to a class of drugs called non-steroidal anti-inflammatory drugs (NSAIDs). They work by inhibiting the enzymes that make prostaglandins, chemicals that promote inflammation, pain and fever, and are necessary for blood clotting.

History of Aspirin : 

History of Aspirin Charles Frederic Gerhardt, was the first to prepare acetylsalicylic acid in 1853 Six years later, in 1859, von Gilm obtained analytically pure acetylsalicylic acid In 1897, scientists at the drug began investigating acetylsalicylic acid 1899, Aspirin was selling it around the world The name Aspirin is derived from A = Acetyl and . " Spirsäure" = an old (German) name for salicylic acid

Pharmacology of aspirin : 

Pharmacology of aspirin Low-dose aspirin (as low as 81 mg) irreversibly inhibits the COX-1 enzyme, by acetylating the serine residue at position 529, consequently impairing the transformation of arachidonic acid to prostaglandin (G2/H2), and TX A2, which is a potent mediator of platelet aggregation and activation. This effect explains the clinical benefit of aspirin in patients with high risk vascular disease Aspirin's effect on COX-2 is minimal in doses <1200 mg

Who Should Take Aspirin ? : 

Who Should Take Aspirin ? Aspirin used as, Analgesic &Antipyretic Rheumatic fever &Rheumatoid Arthritis External applications corns & calluses Colon cancer Cardiovascular applications prophylactically to decrease the incidence of ischemic attacks & unstable angina

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Who Should DEFINITELY Not Take Aspirin? : 

Who Should DEFINITELY Not Take Aspirin? People with active peptic ulcers Those with poor kidney or liver function Patients taking anticoagulant medications Asthma patients

Definition of Aspirin resistance : 

Definition of Aspirin resistance Failure to work clinical aspirin resistance.The inability of aspirin to protect a person from cardiovascular events such as heart attacks and strokes.

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NO WAY

pharmacological Mechanism of Resistance : 

pharmacological Mechanism of Resistance COX-1 activity is not blocked in aspirin-resistant patients but reasons for this had remained unclear A trial with 19 aspirin-sensitive and 19 aspirin-resistant patients who had experienced recent acute coronary ischemia looking at different blood-serum proteins expressed by the two patient groups. aspirin-resistant patients' serum contained raised levels of a vitamin D-binding protein (DBP) . When this protein was incubated with blood from healthy volunteers, it significantly reduced aspirin's inhibitory effect on platelet thromboxane A2 production..

this suggests a completely new mechanism for aspirin resistance : 

this suggests a completely new mechanism for aspirin resistance 1) DBP might directly reduce aspirin's ability to acetylate COX-1's active site OR 2) DBP might bind platelet cytoskeleton proteins that change COX-1's structure making its active site less accessible to aspirin.'  ,

Other mechanisms of resistance : 

Other mechanisms of resistance 1)concomitant intake of other NSAIDs as ibuprofen 2)Genetic polymorphism of enzymes like COX-1, COX-2 or thromboxane A2 synthase 3)Increased reactivity of platelets towards other aggregating factors 4)Increased rate of entry of new platelets into the circulation 5)Alternate pathways of thromboxane synthesis 6)Poor patient compliance

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High risk group: : 

High risk group: 1)Race:

2)Alcoholics : 

2)Alcoholics 3) Drug abuse 4)Patient with a history of heart failure 5)Renal insufficiency 6)Higher prothrombin time and partial thromboplastin time 7) women, the elderly and those taking lower doses of aspirin most likely to be aspirin resistant.

Diagnosis of AR : 

Diagnosis of AR Platelet-Function Testing 1)light transmittance aggregometry (LTA) This assay measures the increase in light transmittance across platelet-rich plasma and development of clumps in response to different agonists (ADP, collagen, arachidonic acid). AR is ≥20% platelet aggregation with 1 mg/mL arachidonic acid and ≥70% aggregation with 10 mol/l ADP despite regular intake of aspirin

2)platelet function analyzer PFA-100 device : 

2)platelet function analyzer PFA-100 device acts like an injured artery, where high shear stress conditions are present. Hence, platelet function is evaluated by the time needed to form a platelet plug to occlude the gap present in this device. Using this test, AR is generally defined as a closure time of <164 s despite regular aspirin intake.

3)TX A2 pathway measures : 

3)TX A2 pathway measures serum TX B2 urine 11-dehydroTX B2

Management1st step : 

Management1st step Increasing the aspirin dose Adding omega-3 fatty acids Mediterranean-style diet Next: Take steps to reduce your risk for cardiovascular disease. Risk is determined by age, gender, family and medical history, ­smoking, cholesterol levels and other cardiovascular risk markers, blood pressure, weight and whether you have diabetes. Follow up by monitor fibrinogen levels

2nd step : 

2nd step For those who don't have heart disease and want to prevent it, take fish oil, vitamin E and bromelain For those with atherosclerosis (fatty buildup in the arteries), take nattokinase and fish oil. For those with elevated fibrinogen, take nattokinase and fish oil, and then add vitamin E and bromelain if lab tests indicate fibrinogen has not decreased after two months.

Fish oil : 

Fish oil Research has shown that patients with coronary artery disease (plaque in the arteries of the heart) who were given fish oil supplements had a mild-to-moderate regression of atherosclerosis as measured by angiography. . Best fish sources: Oily, cold-water fish (salmon, herring, sardines, mackerel, anchovies), Vitamin E. 800 international units (IU) to 1,200 IU daily. this antioxidant has natural blood-thinning properties. Bromelain . Found in pineapples Take 500 mg three times daily

Nattokinase : 

Nattokinase this enzyme is made from fermented soybeans. With its strong fibrin-dissolving effect 2,000 fibrinolytic units (FU) to 4,000 FU of a nattokinase supplement twice daily

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Home taking points : 

Home taking points Long-term aspirin administration in patients at high risk of occlusive vascular events reduced up to 34% of nonfatal myocardial infarction (MI), 25% of nonfatal stroke, and 18% of all-cause mortality Failure of Aspirin to work is AR Unstable angina, stroke and cardiac death. Of patients, 22.2% (n = 52) were aspirin resistant by PFA-100. the clinical implications of aspirin resistance are explored in various cardiovascular disease states, including diabetes mellitus, hypertension, heart failure, and other similar disorders where platelet reactivity is enhanced. Pt with AR is poorly asymptomatic diagnosed by PFT& TX A2 pathway measures Facing the problem by increasing dose ,vit E,&Omega3

For attention : 

For attention THANK YOU