The development of new and improved medication has been a boon to human civilization. The advancements in modern medicine have propelled the human race to live longer and have healthier lives, leaving behind the times when having an illness or experiencing a stroke spelled a negative outcome, frequently resulting in premature death more often than not. The field of anticoagulant medication research has also made great strides in improving the effectiveness and efficiency of the blood thinner class of medications, with the use Xarelto anticoagulant helping certain individuals prevent life-threatening complications from the likes of thrombosis and emboli. In this article, we will discuss anticoagulant medication use, specifically focusing on Xarelto also know by its generic name, Rivaroxaban; a relatively new anticoagulant medication on the market. We will go over its uses and mechanism of action, as well as detail Xarelto dosing, Xarelto indications, and the side effects of Xarelto.
The use of blood thinning medication has become standard protocol for the treatment and prevention of venous thromboembolisms over the last couple of decades, which includes the treatment of both deep vein thrombosis (DVT), and pulmonary embolisms (PE). While essentially two sides of the same coin, DVT is often the predecessor to PE, with the latter being the more serious and life threating of the two. Both stem from the body’s normal physiological response to vessel damage or injury, by the activation of platelets and the coagulation cascade. Here the body responds to signals meant to facilitate the repair of damaged vessels through the use of platelets and clotting factors, helping seal the area of endothelial damage, but due to extraordinary circumstances, this process can become over-exaggerated leading to excessive clotting, potentially becoming hazardous. It is estimated that the normal human body experiences thousands of vessel injuries every single day, but go entirely unnoticed, as the body can effectively utilize these blood constituents and the coagulation cascade to produce clots to stop excessive bleeding, and once repair is completed, the body effectively reabsorbs and recycles the leftover clot material, maintaining homeostasis.
What is Xarelto (Rivaroxaban)?
Developed and manufactured by the Bayer pharmaceutical company, who happens to also be the makers of the most popular brand of Aspirin on the market. Xarelto anticoagulant was the first orally active, direct factor Xa inhibitor available on the market, approved for use by Xarelto Canada health authorities in 2008 and the FDA in 2011. It works by directly inhibiting part of the coagulation cascade in order to prevent the formation of clots in the body. While other anticoagulants focus on inhibiting platelet aggregation and the cofactors that affect the coagulation cascade in an indirect manner, Xarelto dosing directly targets Factor Xa which is a vital step in the production of fibrous clots.
Producing clots is a multistep process, involving over 50 types of blood constituents composing of platelets and clotting factors that all work in concert to stop bleeding where necessary. Platelets are first to act, and with the help of Von Willebrand Factor begin sticking to exposed collagen that appears after endothelial vessel injury. Once attached to the site of injury these platelets begin to swell, increasing in size, as well as start to release granules including ADP and Thromboxane A2 signaling more platelets to come and plug the vessel opening. At this point, a platelet plug has formed but is currently unstable and can easily become dislodged if not properly secured to the exposed endothelium. This is when the coagulation cascade becomes initiated which come in two flavors, Intrinsic and Extrinsic pathways. While having different points of activation, they both have a common area of convergence which is the activation of Factor X to Factor Xa, which happens to be the main site for Xarelto dosing mechanism of action. From here newly activated Factor Xa promotes the activation of Prothrombin (aka Factor II) to Thrombin (aka Factor IIa), which in turn activates Fibrinogen (aka Factor I) to Fibrin, forming the clot. Initially this newly formed Fibrin mesh is weak and can easily be broken apart, as the fibrin fibres 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. If proper Xarelto dosing were to be implemented at this step, the entire process of blood coagulation would be reduced, adequately preventing the formation of potentially harmful blood clots or at the very least provide more time for physicians to implement lifesaving procedures.
There is, however, instances where certain individuals are more prone, compared to the general population, to developing clots that could potentially become harmful. These could be genetic factors, such as in the case of factor V Leiden mutation whereby over-activation of Factor V in their blood stream; responsible for aiding in the activating Factor Xa, leads to an increased tendency for abnormal and potentially dangerous blood clots to form. Patients recovering from surgical procedures are also at high risk for developing clots, whereby tissue injury due in part to the invasive nature of surgery can cause foreign material such as collagen and fat to be released into the blood stream, which are potential activators of platelets and the coagulation cascade. Also extended bed rest which is common after surgeries promote an environment of blood stasis, as muscle movement is required to continuously pump blood black to the heart, but instead pools in the legs, and explains why most blood clots found in bed bound post-surgical patients are found in the lower extremities in the form of deep vein thrombosis(DVT). Owing partly to the nature of gravity, blood furthest from the heart has a harder time reaching the rest of circulation and is more likely to become static, promoting the clotting process. Once a clot is formed in a lower extremity, it can prohibit adequate blood flow resulting in pain, swelling, and discoloration; the hallmarks of a DVT. The real threat is the ability for DVTs to dislodge becoming an emboli which have the potential to travel throughout the venous circulatory system, and is very likely to become lodged in the lung tissue, called a pulmonary embolus (PE). The lungs are vital for human survival, and blocking any portion of blood supply to them can result in shortness of break, chest pain, and even sudden death if not treated in time. The aforementioned phenomena correlate with the proposed pathogenesis of venous thrombosis called, Virchow’s Triad, whereby the combination of blood stasis, hypercoagulable states, and vessel injury all contribute to thrombosis, of which Xarelto dosing aims to remedy.
Xarelto dosing is currently approved by Xarelto Canada health authorities and the FDA for the prevention of blood clot formation in patients who have undergone knee or hip replacement, as well as for the prevention and treatment of blood clots that develop in the deep veins of the lower extremity; deep vein thrombosis (DVT), and also for its complication; pulmonary embolism (PE). Patients suffering from a cardiac condition called atrial fibrillation (non-valvular) are also approved for Xarelto dosing as blood clots can also be a consequence of this potentially fatal disorder. Atrial fibrillation is an ailment whereby the normal beats of the heart become out of sync and instead give an irregular heart rhythm known as an arrhythmia. Individuals with this irregularity have a substantial increase in their risk of ischemic stroke, about 3 to 5 times greater risk than those without atrial fibrillation, with an estimated 15% of all strokes being atrial fibrillation related. The reason behind this is linked to hearts ability to pump out blood, and its efficiency for doing so. In the typical atrial fibrillation patient, the heart has difficulty pushing the majority of its contents out through the aorta and instead leaves an abnormal amount of blood to pool in the heart chambers. It is this pooling of blood that is of concern to many practicing physicians, as blood not in motion has a tendency to begin clotting, leading to the development of blood clots which now have easy access to the arterial-venous system to potentially travel to other parts of the body such as the brain, leading to a stroke.
Xarelto INR/ Rivaroxaban INR
The scientific method for measuring the adequacy of anticoagulation in an at-risk patient for the better part of half a century has for the most part been measuring the INR; International Normalized Ratio. This method is under scrutiny as newer and more improved anticoagulants hit the market. Warfarin, an anticoagulant used since the 1950’s primarily used INR to measure a patient’s level of anticoagulation, owing to its Warfarin’s variable dosing and narrow therapeutic index, requiring frequent blood draws for testing. INR was tailored to determine the effectiveness and safety of vitamin K antagonists, of which Warfarin is, and therefore is meaningless for measuring Xarelto INR/Rivaroxaban INR as it affects a completely different pathway of the coagulation cascade. While obtaining Xarelto INR/Rivaroxaban INR is still possible, it fails to accurately predict the effectiveness of therapy, and can vary from case to case. However, if anticoagulation levels were to be required for a particular rivaroxaban dose, such as before urgent surgery or in suspected cases of overdose, a PT (prothrombin time) assay using a thromboplastin reagent sensitive to rivaroxaban may be useful it times of emergency, with an anti-Factor Xa chromogenic assay being the most suitable for quantitative assessment if time permits. While there isn’t currently a gold standard method for measuring the exact effectiveness of Xarelto dosing, more useful tests methodologies are currently under development. However, with the tests mentioned above, combined with fixed Xarelto dosing and its predictable anticoagulation activity, physicians can safely use this newer class of medication while still avoiding any potential side effects of Xarelto.
Xarelto side effects/ Rivaroxaban side effects
Most if not all pharmaceutical medication carries some sort of unwanted side effects that may make the individual using them feel unwell. All anticoagulants carry a common undue attribute that occurs if used improperly or is not metabolized efficiently by the host, and this holds true with Xarelto side effects as well. The occurrence of abnormal bleeding in the form of bleeding gums, prolonged bleeding from cuts, and bloody stools are some of the more common side effects seen in patients using this medication, however, some Xarelto side effects may not need any medical attention at all as they may disappear once the body gets use to the treatment. Using Xarelto in combination with other medications or substances may also exaggerate these side effects, as they may augment the level of medication found the blood stream. Diet considerations emphasized as with other anticoagulants such as Warfarin, doesn’t hold true with Xarelto, as it hasn’t been documented to have any adverse effects with any foods or drink, however, combinations such as Xarelto and alcohol may increase the risk of bleeding and should be discussed with a doctor before consuming large amounts. It is important to note that individuals who are prone to bleeding (ex. Inherited bleeding disorders), have uncontrolled high blood pressure or have recently experienced a hemorrhagic stroke should not be prescribed a rivaroxaban dose as uncontrolled bleeding is a serious consequence during these circumstances.
Common side effects
-Easy bruising or bleeding (nosebleeds, heavy menstrual bleeding, bleeding gums)
-Pain, swelling or draining from previous wound or needle injection
-Excessive bleeding from wounds that will not cease
-Discolored urine (Red, Pink, or Brown color)
-Headache, dizziness, fainting
-Muscle pain, Itching
-Pain/weakness in arms or legs
It is very important to speak to your primary care physician immediately if you are experiencing any of the listed Xarelto side effects/Rivaroxaban side effects as he/she may be able to help prevent or reduce their occurrence, otherwise, seek emergency medical care at the nearest clinic or hospital if your doctor is not available.
Xarelto Dosing Considerations
Xarelto is available in 10mg, 15mg, and 20mg formats, and there are many factors and considerations when prescribing an anticoagulant. Taking into account the patient’s overall health, such as measuring kidney and liver function are very important as most pharmaceuticals are cleared from the body this way. If an individual were to be prescribed a Xarelto dosing while simultaneously having a dysfunction in any of these organs it could potentially increase the risk of experiencing excessive bleeding due to higher therapeutic levels in the bloodstream. Here are the various indicated dosing regimens currently implemented.
Adult Dosing (Canadian Guidelines)
Stroke risk reduction in Non-valvular Atrial Fibrillation
-CrCl > 50ml/min: 20mg once a day with evening meal
-CrCl 30-49ml/min: 15mg once a day with evening meal
– CrCl <30ml/min: avoid use due to increased bleeding risk Treatment of DVT/PE -15mg twice a day with food for first 3 weeks, and then transition to 20mg once a day with food for the remainder of treatment period DVT/PE reduction in risk of reoccurrence -20mg once a day with food for duration of treatment period Post hip or knee replacement surgery DVT prophylaxis (initial dose to be taken 6-10 hours after surgery for stable patients) -Hip replacement: 10mg once a day for 35 days -Knee replacement: 10mg once a day for 12 days Missing a regularly scheduled dose of Xarelto can be dangerous, putting the individual at risk once again for a vascular event. It is important to stick to the regimen outlined by the prescribing physician and to take Xarelto as indicated. If Regularly Scheduled Dose Is Missed: -Patients taking 15mg twice a day: Take both pills (30mg) immedicably at the same time, and continue regularly scheduled doses -Patients taking 10mg, 15mg, or 20mg once a day: Take missed dose immediately, and continue regularly scheduled dose.