Our body consists of a rich vascular system that carries blood to tissues and organs imperative for our survival. Blood is abundant in oxygen and nutrients that provide the body with the energy needed in order to maintain their function, as without it vital organs will eventually shut down, inevitably causing us to die. The sudden loss of blood, however, isn’t the only manner our bodily organ can be starved of oxygen, for there are innate mechanisms in place that when activated can cause the developments of clots plugging up vascular pathways to the heart, lungs, and even the brain. Through the process of blood coagulation, factors in our blood stream come together to form thrombi or blood clots in an attempt to stop any internal bleeding the body senses. While this is a normal phenomenon happening every single day, under extreme circumstances these clots can break off wreaking havoc elsewhere in the body, or even cause death. In this article, we will discuss various anticoagulant medications, and explain how do anticoagulants work, and when to use anticoagulants. We will also shed some light on anticoagulant vs antiplatelet medications and their differences in practical use.
The Importance Of Coagulation
It is estimated the body experiences thousands of minute vascular ruptures daily due to naturally occurring wear and tear, but go unnoticed as coagulation factors activate preventing blood loss, granting the body time to repair the injury. It is this level of homeostasis (stable equilibrium) that speaks volumes of the progressive nature of the human body; an advanced level of automation that takes control complicated and grueling internal maintenance without even the slightest thought. Because homeostatic mechanisms are out of our direct control, there is room for the possibility for errors to occur unknowingly, potentially leading to detrimental consequences. Choosing anticoagulant VS antiplatelet medications is vital for patient survival, as choosing an ineffective treatment could result in patient death.
There are two main important mechanisms that need to occur in order for adequate cessation of blood to commence; platelet plug formation and blood coagulation.
Platelet plugs are the initial step for the repair of vascular openings. Platelets (also called thrombocytes) adhere to damaged vascular surfaces, immediately beginning to swell after contact with the endothelial lining of the vessel. This change in size helps stop bleeding and also facilitates the release of granules that contain multiple clotting factors that aid in making the platelets extra stickyand signaling the activation of nearby platelets by way of the enzyme thromboxane A2and ADP release. Platelets will continually call on more and more platelets until a platelet plug is formed, and is usually successful In blocking blood loss of small vascular opening, but can become dislodged unless the subsequent process of blood coagulation occurs,reinforcing the plug making it stable. During this phase choosing anticoagulant vs antiplatelet medications errs on the side of the latter as a preventative measure to clot induced disease.
Blood coagulation is the mechanism of blood clot creation and is a vital step in stopping excessive blood loss. A clot begins to form within seconds to minutes depending on the severity of the trauma to the blood vessel. Activator substances from platelets, blood proteins, and the damaged vascular wall all help initiate the clotting process. There are over 50 important substances that cause and affect blood coagulation found in blood and tissues. While some will promote coagulation to form blood clots, other promote the opposite, helping dissolve blood clots that have served their purpose. It is during this phase that many treatments forbloodclotrelated events such as pulmonary embolism and stroke are implemented helping reduce their occurrence. A protein called Prothrombin also known as Factor II, attaches to analogous receptors found on the platelet plug formed prior, and with the aid of Prothrombin Activator proteins, Prothrombin is converted to the protein enzyme Thrombin. This enzyme can now act on Fibrinogen, which has now embedded itself into the site of injury and is converted into Fibrin. Fibrinogen, also known as Factor I is essential in the clot formation process owing to its large molecular size and its polymerization into Fibrin forming the clot. Initially this newly formed Fibrin mesh is weak and can easily be broken apart, as the fibrin fibers are not cross-linked, but a substance called Fibrin-Stabilizing Factor present in blood plasma becomes activated helping to greatly strengthen the fibrin reticulum giving us a true clot composed of meshwork running in all directions entrapping blood cells, platelets, and plasma guaranteeing adherence to any vascular opening, preventing blood loss. Once the site of injury has been healed, the fibrin and other products of clot formation are broken down and cleared by the body by the process of fibrinolysis with the help of Plasmin protein, Factor V, Factor VIII, and Factor XII.It is this balance that helps keep homeostasis in check, and also gives physicians the knowledge to help augment these processes in patients considered at risk for excessive clot formation, such as the use of anticoagulation and atrial fibrillation clot risk patients. During this phase choosing between anticoagulant vs antiplatelet medications errs on the side of the former as inhibiting the coagulation cascade is the top priority.
Anticoagulation medications are considered invaluable for prevention and treatment in patients suffering the effects of ischemia due to blood clots; cellular tissue death as aresult of lack of oxygenated blood. Ischemia may occur due to emboli; a dislodged thrombus that is now circulating in the blood vasculature with the high probability of becoming lodged in the lungs causing a PE (pulmonary embolus), or even the brain causing a stroke. It is up to an experienced physician to recognize the signs of an impending emboli formation and weigh the benefits of anticoagulant vs antiplatelet medications to best suit the immediate needs of the patient.
With the use of anticoagulants, blood becomes less viscous by inhibiting the factors that promote clot formation, helping decrease the chances of tissue death due to rogue clots. There are many different types of anticoagulants all serving a similar purpose, but when to useanticoagulants is the real question as each comes with their own benefits and drawbacks depending on the condition of the patient. Knowing the science behind how do anticoagulants work and choosing the right time to implement anticoagulant vs antiplatelet medication gives physicians the knowledge of risks involved when tailoring a specific treatment plan for patients suffering from events such as a heart attack or stroke.
One of the most commonly used anticoagulant medications in North America whose origins can be traced back to the 1940s as a pesticide used against mice and rats,it wasn’t until in the early 1950s when it was discovered that warfarin exhibited unique properties that could be utilized safely and effectively as a medication for preventing blood clots. Warfarin for strokes and clots works by inhibiting vitamin K epoxide reductase, an enzyme that aids in the conversion of vitamin K found in leafy greens we ingest, into coagulation factors (II, VII, IX,X, Protein C &S) needed to create clots. Warfarin, however, has a few caveats for its use, as many commonly used medications as well as some foods can alter the effectiveness and safety of the drug, with the most common side effect being abnormal bleeding elsewhere in the body. Also, routine blood monitoring is required to ensure proper dosing and safety, but if used properly can be highly effective. Warfarin for anticoagulation and atrial fibrillation patients often go hand in hand, as the rhythm disorder promotes the formation of clots in the heart which can travel elsewhere in the body. When physicians are choosing anticoagulant vs antiplatelet medications for the prevention of life-threatening phenomenon such as strokes, warfarin has proven itself as a lifesaving medication.
Often used in conjunction with Warfarin as a bridging anticoagulant, as Heparin is faster acting in comparison. Warfarin may take a couple of days to reach therapeutic levels, therefore heparin is utilized to help bridge this gap ensuring adequate prevention of clot formation from the start of treatment. Heparin may be used alone as well for the prevention of clots and is actually preferred in some cases, such as in pregnant patients, as warfarin has been documented to cause birth defects. It works by binding to Anti-thrombin III and activating it. By doing this the clotting factor Xa and Thrombin become inactivated preventing clot formation.
A relatively new anticoagulant to the market that has approved by the FDA and Health Canada in 2010, and 2008. Pradaxa (Dabigatran) is often considered an alternative to Warfarin as it doesn’t require routine blood monitoring but offers similar results in terms of efficacy. It works by directly inhibiting thrombin, a key factor in clot formation and is approved for reducing the risk of strokes and in patients with atrial fibrillation.
Being first developed in Japan as an anticoagulant used in preventing clots post orthopedic surgery, Savaysa dosing has recently been approved by the FDA as of 2015 for also the prevention of stroke and systemic emboli in patients with non-valvular atrial fibrillation. Edoxaban works by inhibiting Factor Xa, and prothrombinase helping reduce thrombin formation in at-risk patients.
Similar in themechanism of action to the aforementioned anticoagulant, Rivaroxaban also works by directly inhibiting Factor Xa helping prevent clot formation. It was documented to have lower rates of serious and fatal bleeding event compared to warfarin use, but higher rates of gastrointestinal bleeding as a tradeoff. Rivaroxaban dosing is approved for patients suffering from non-valvular atrial fibrillation and prevention of venous thromboembolism in patients having undergone knee and hip surgery.
Approved for treatment and prophylaxis of deep vein thrombosis, as well as reduction of stroke risk and systemic embolism in patients with non-valvular atrial fibrillation, Apixaban also works by directly inhibiting factor Xa in thrombus formation. It has also proven beneficial in the treatment and prevention of pulmonary embolism, a potentially life-threatening condition resulting from emboli becoming stuck in the lung parenchyma, often leading to sudden death. It has been documented that Apixaban has similar efficacy to warfarin for anticoagulation and is associated with lower risk of intracranial bleeding.