Our bodies consist of muscle, tissue, and organs, connected by a rich and diverse network of vascular highways delivering an essential component to our survival; blood. It is the facilitator of oxygen transfer, nutrient deliverance, and waste disposal that our bodies depend on to live. Yet it is all too common for a cut or wound to allow this essential life sustaining fluid to ooze out potentially putting your life at risk. We’ve all experienced minor cuts from time to time, retracting at the sight of blood leaking out from the newly broken skin, but due to the effect of platelets in our blood stream, the blood starts to curdle, congealing into a vascular plug, putting a stop to excessive blood escaping from the body, essentially saving our lives, as without platelets we would continue to bleed without end. Although this innate feature of the human body is imperative for survival in this rough and tumble world, it can sometimes work out of our favor, such as in the development of clots that can travel to vital organs of the body such as the brain, leading to potentially fatal consequences like strokes. In this article, we will discuss how modern antiplatelet therapy is implemented in a clinical setting, learn the science behind how do antiplatelets work, as well as go over some differences between antiplatelet VS anticoagulant medications. A commonly used antiplatelet drugs list will also give a better understanding on why certain therapies are chosen over others.
Stopping and preventing excessive blood loss is something the human body is incredibly good at, as it has innate mechanisms in place to recognize vessel injury and immediately start the repair process if required. Our blood plays an important part in this repairing process as it carries many of the factors and blood constituents that act to limit blood loss and facilitate vessel repair, with platelets being at the forefront of this action.
During an event where vessel injury occurs, platelets (thrombocytes) are the first to spring into action. Glycoproteins on the surface of platelets normally do not adhere to normal endothelial linings of blood vessels, however, if this blood vessel lining becomes injured in anyway, surface glycoproteins on platelets causes them to become sticky and adhere to the site of damage. By doing this, the vessel opening is plugged, not allowing further blood to continue leaking, much like repairing a leaky pipe. Once this process is started, platelets begin to secrete granules that contain multiple active factors such as ADP and Thromboxane A2which in turn attract more and more platelets to adhere to the damaged vessel forming a platelet plug. Is during this phase of blood clot formation, physicians can decide whether to choose antiplatelet vs anticoagulant medications to best suit the patient’s needs.
The next and equally important event to occur in blood clot formation is the coagulation cascade. This is where a series of coagulation factors sequentially trigger to ultimately produce a stable blood clot, helping preserve blood volume. It does that by utilizing over 50 different substances that become activated once a vessel injury occurs, with the ultimate goal of producing Fibrin; a tough fibrous protein that enhances the strength of the platelet plug formed prior, forming a clot that helpsstop blood loss. Once the healing process is completed, a process called fibrinolysis occurs; effectively breaking down and reabsorbing the clot that has served its purpose. During the coagulation cascade phase choosing antiplatelet VS anticoagulant medications errs on the side of the latter as the clot is now much later in its development.
The prevention of thrombus and emboli formation are the main reasons physicians employ medications that inhibit platelet and coagulation factors from becoming active in the first place. Modern medicine has allowed having the knowledge of how these complex processes work and thereby allow for the augmentation or promotion of a hypocoagulable state (less blood clotting environment) helping stroke risk patients increase their chances of survival. One such practice is the utilization of antiplatelet therapies for the treatment of cardiovascular disease by assessing stroke risk with the CHA2DS2 score. This risk assessment helps physician choose whether a patient will benefit from antiplatelet VS anticoagulant medication.
The CHA2DS2 score is a risk assessment to determine the likely chances of a stroke in individuals with atrial fibrillation and other serious heart arrhythmias associated with thromboembolic events. It helps physicians determine whether a patient will benefit from antiplatelet therapy, and if so when to best choose antiplatelet VS anticoagulant medications. Each letter in “CHADS” corresponds to an attribute that has been linked to the increased annual risk of developing a stroke, with appropriate points given if the patient in question were to exhibit such attributes, currently or in the past. This risk assessment has been further refined by adding additional criteria to make a more accurate prediction of the incidence of stroke in low-risk patients. By adding “VASc” to the existing acronym, we have now come to use the CHA2DS2-VASc score which has been shown to outperform the previous score assessment in multiple patients groups with atrial fibrillation and is recommended for physicians to follow by the American college of cardiology/American Heart Association Task Force.
C-Congestive Heart Failure: 1 point
H- Hypertension (treated or untreated): 1 point
A-Age ≥75 years: 2 points
D-Diabetes Mellitus: 1 point
S-Stroke or TIA or thromboembolism in the past: 2points
V-Vascular Disease (ex. Myocardial infarction, peripheral artery disease):1 point
A-Age (65-74 years):1 point
Sc-Sex Category (female gender): 1 point
A higher score corresponds to a greater risk of a stroke, with the opposite being true as well. Depending on the patient, choosing between antiplatelet VS anticoagulant medications can have substantial outcomes on overall survival, with anticoagulants being reserved for high-risk individuals. Guidelines set by The European Society of Cardiology (ESC) and the National Institute for Health and Care Excellence (NICE) recommend that any persons with a low-risk score (0 for males, and 1 for females) do not require any sort of anticoagulant to be implemented, but some physicians will prescribe low doseAspirin, an antiplatelet medication as a precaution. Patients with an intermediate score (1 for males, and 2 for females) are considered for anticoagulant medications based on overall health status, and patient preference for either Aspirin or Warfarin. Those considered at high risk (≥2 in males, and ≥3 in females) have been found to largely benefit from oral anticoagulation medication with warfarin being the anticoagulant of choice, with newer alternatives being available if approved. In patients who have recently been diagnosed with acute coronary syndrome (ACS), or have undergone percutaneous coronary intervention (PCI) don’t have to choose between antiplatelet VS anticoagulant medications, as they are often put on both for maximum stroke risk prevention.
By preventing the constituents that promote platelet aggregation; Thromboxane A2 and ADP, efficient anticoagulation can be achieved. All “blood thinning” medication carries a common side effect of bleeding if not used as instructed and knowing the science behind how do antiplatelets work gives physician’s knowledge to use them safely and effectively. The following is an antiplatelet drugs list of some of the most commonly used, and newer clot-preventing medications used today. They all have the primary purpose of slowing the body’s physiologic response to blood vessel injury and work towards the goal of preventing blood clots decreasing the risk of strokes.
Often used to treat a medical condition called Essential thrombocythemia (ET), whereby there is an overproduction of platelets being produced by the body, and in rare instances further develops into Acute Myeloid Leukemia or Myelofibrosis. The main complication of having ET is the development of blood clots due to the overabundance of platelets, among other symptoms such as visual disturbances, fainting, and headache. Anagrelide works by inhibiting the development of immature megakaryocytes into mature platelets found in the bone marrow, thereby reducing the overproduction of platelets in the body.
Also known as acetylsalicylic acid, it has multiple useful attributes, being commonly used as an antipyretic, for analgesia, an anti-inflammatory and can be used long term to help prevent heart attacks, strokes, and blood clots in high-risk patients due to its inhibitory action against platelet aggregation. It achieves many of these actions due to its effect on reducing the production of prostaglandins and thromboxane A2; which are primarily involved in inflammatory processes and clotting respectively. An unfortunate side effect of using Aspirin, however, is the increased risk of gastrointestinal bleeding, owing to its effects of mucosal erosion of the gastric lining.
Being hailed as of one of the most important medications by the World Health Organization (WHO), Clopidogrel is used to prevent heart attack and stroke in high-risk individuals, as well as helping maintain circulation in distal extremities in those suffering from Peripheral Vascular Disease. It is also used in combination with or alternative to Aspirin for thrombus prevention in individual having undergone coronary stent placement. It works by inhibiting platelet aggregation and stopping platelets from sticking to blood vessel walls or injured tissue by irreversibly blocking ADP receptors found on platelet cell membranes. Due to its limited effect on the gastric lining of the stomach, Clopidogrel is often recommended in those with Aspirin-induced gastric ulcers. It is also important to note that persons using proton pump inhibitors (a common adjunct medication to help prevent gastric ulcers in patients taking Asprin/NSAIDs) may increase adverse cardiac outcomes when taken in conjunction with Clopidogrel and is therefore not advisable.
Working in much the same way as Clopidogrel, Prasugrel is also an ADP receptor blocker helping reduce platelet aggregation. However, Prasugrel was found to be more effective, acting more rapidly, more consistency, and overall working to a greater extent when used in patients with Coronary Artery Disease, as well as having undergone PCIthan the aforementioned antiplatelet medication. Another advantage over Clopidogrel is its safe use with proton pump inhibitors, as there is little to no interaction leading to reduced antiplatelet effects.
Used to prevent thrombotic events such as stroke and heart attack, Ticagrelor also works in the same way as the medications mentioned above; blocking ADP receptors on platelet cell membranes. However, the binding site of this medication slightly different from the previous drugs making the blockage of ADP reversible helping combat excessive bleeding side effects of these types of medications. During clinical trials, it was found that Ticagrelor exhibited better mortality rates than Clopidogrel in treating patients with Acute Coronary Syndrome, but had a higher chance of developing non-lethal bleeding.
Approved for reducing the rate of thrombotic cardiovascular events such as myocardial infarction in patients with non-ST elevation acute coronary syndrome, and frequently used during PCI procedures, Tirofiban inhibits platelet aggregation by blocking glycoprotein IIb/IIIa receptors found on platelets. Much like most antiplatelet medications, the most common side effect is excessive bleeding.
Derived from himbacine, a natural product found in the bark of Australian magnolias, it was originally developed to be a muscarinic antagonist for use in Alzheimer’s patients but failed due to inadequate results. Later an analog of the substance was derived and found to have substantial benefit as a thrombin receptor antagonist; preventing platelet aggregation. Vorapaxar is indicated for use in patients with a history of myocardial infarction or peripheral arterial disease to prevent thrombotic cardiovascular events.
Dipyridamole works by inhibiting adenosine and phosphodiesterase enzymes, thereby increasing intracellular levels of cAMP, a cellular substance responsible for signal transduction, and in the case of platelets help block platelet aggregation when increased levels of cAMP are available. Another use is its ability todilate blood vessels to help improve circulation. It is often used in conjunction with aspirin in patients with a history of stroke to prevent future embolic events.