Anticoagulant


An anticoagulant, commonly known as a blood thinner, is a chemical substance that prevents or reduces the coagulation of blood, prolonging the clotting time. Some occur naturally in blood-eating animals, such as leeches and mosquitoes, which help keep the bite area unclotted long enough for the animal to obtain blood.
As a class of medications, anticoagulants are used in therapy for thrombotic disorders. Oral anticoagulants are taken by many people in pill or tablet form, and various intravenous anticoagulant dosage forms are used in hospitals. Some anticoagulants are used in medical equipment, such as sample tubes, blood transfusion bags, heart–lung machines, and dialysis equipment. One of the first anticoagulants, warfarin, was initially approved as a rodenticide.
Anticoagulants are closely related to antiplatelet drugs and thrombolytic drugs by manipulating the various pathways of blood coagulation. Specifically, antiplatelet drugs inhibit platelet aggregation, whereas anticoagulants inhibit specific pathways of the coagulation cascade, which happens after the initial platelet aggregation but before the formation of fibrin and stable aggregated platelet products.
Common anticoagulants include warfarin and heparin.

Medical uses

The use of anticoagulants is a decision based on the risks and benefits of anticoagulation. The biggest risk of anticoagulation therapy is the increased risk of bleeding. In otherwise healthy people, the increased risk of bleeding is minimal, but those who have had recent surgery, cerebral aneurysms, and other conditions may have too great a risk of bleeding. Generally, the benefit of anticoagulation is preventing or reducing the progression of a thromboembolic disease. Some indications for anticoagulant therapy that are known to have benefit from therapy include:
In these cases, anticoagulation therapy prevents the formation or growth of dangerous clots.
The decision to begin therapeutic anticoagulation often involves the use of multiple bleeding risk predictable outcome tools as non-invasive pre-test stratifications due to the potential for bleeding while on blood thinning agents. Among these tools are HAS-BLED, ATRIA, HEMORR2HAGES, and CHA2DS2-VASc. The risk of bleeding using the risk assessment tools above must then be weighed against thrombotic risk to formally determine the patient's overall benefit in starting anticoagulation therapy.
There is no evidence to indicate that adding anticoagulant therapy to standard treatment has a benefit for people with cerebral small vessel disease but not dementia, and there is an increased risk of a person with this disease experiencing a bleed with this approach.

Adverse effects

The most serious and common adverse side effects associated with anticoagulants are increased risk of bleeding, both nonmajor and major bleeding events. The bleeding risk depends on the class of anticoagulant agent used, the patient's age, and pre-existing health conditions. Warfarin has an estimated incidence of bleeding of 15–20% per year and a life-threatening bleeding rate of 1–3% per year. Newer non-vitamin K antagonist oral anticoagulants appear to have fewer life-threatening bleeding events than warfarin. Additionally, patients aged 80 years or more may be especially susceptible to bleeding complications, with a rate of 13 bleeds per 100 person-years. Bleeding risk is especially important to consider in patients with renal impairment and NOAC therapy because all NOACs, to some extent, are excreted by the kidneys. Thus, patients with renal impairment may be at higher risk of increased bleeding.
In people with cancer, a systematic review has found warfarin had no effect on death rate or the risk of blood clots. However, it did increase the risk of major bleeding in 107 more people per 1000 population and minor bleeding in 167 more people per 1000 population. Apixaban had no effect on mortality, recurrence of blood clots in blood vessels, or major or minor bleeding. However, this finding comes only from one study.
Nonhemorrhagic adverse events are less common than hemorrhagic adverse events but should still be monitored closely. Nonhemorrhagic adverse events of warfarin include skin necrosis, limb gangrene, and purple toe syndrome. Skin necrosis and limb gangrene are most commonly observed on the third to eighth day of therapy. The exact pathogenesis of skin necrosis and limb gangrene is not completely understood but it is believed to be associated with warfarin's effect on inhibiting the production of protein C and protein S. Purple toe syndrome typically develops three to eight weeks after initiation of warfarin therapy. Other adverse effects of warfarin are associated with depletion of vitamin K, which can lead to inhibition of G1a proteins and growth arrest-specific gene 6, which can lead to increased risk of arterial calcification and heart valve, especially if too much Vitamin D is present. Warfarin's interference with G1a proteins has also been linked to abnormalities in fetal bone development in mothers who were treated with warfarin during pregnancy. Long-term warfarin and heparin usage have also been linked to osteoporosis.
Another potentially severe complication associated with heparin use is called heparin-induced thrombocytopenia immune-mediated and 2) non-immune-mediated. Immune-mediated HIT most commonly arises five to ten days after exposure to heparin. Pathogenesis of immune-mediated HIT is believed to be caused by heparin-dependent immunoglobulin antibodies binding to platelet factor 4/heparin complexes on platelets, leading to widespread platelet activation.

Interactions

Foods and food supplements with blood-thinning effects include nattokinase, lumbrokinase, beer, bilberry, celery, cranberries, fish oil, garlic, ginger, ginkgo, ginseng, green tea, horse chestnut, licorice, niacin, onion, papaya, pomegranate, red clover, soybean, St. John's wort, turmeric, wheatgrass, and willow bark. Many herbal supplements have blood-thinning properties, such as danshen and feverfew. Multivitamins that do not interact with clotting are available for patients on anticoagulants.
However, some foods and supplements encourage clotting. These include alfalfa, avocado, cat's claw, coenzyme Q10, and dark leafy greens such as spinach. Excessive intake of the food mentioned above should be avoided while taking anticoagulants, or if coagulability is being monitored, their intake should be kept approximately constant so that anticoagulant dosage can be maintained at a level high enough to counteract this effect without fluctuations in coagulability.
Grapefruit interferes with some anticoagulant drugs, increasing the time it takes for them to be metabolized out of the body, and should be eaten with caution when on anticoagulant drugs.
Anticoagulants are often used to treat acute deep-vein thrombosis. People using anticoagulants to treat this condition should avoid using bed rest as a complementary treatment because there are clinical benefits to continuing to walk and remaining mobile while using anticoagulants in this way. Bed rest while using anticoagulants can harm patients in circumstances in which it is not medically necessary.

Types

Several anticoagulants are available. Warfarin, other coumarins, and heparins have long been used. Since the 2000s, several agents have been introduced that are collectively referred to as direct oral anticoagulants, previously named novel oral anticoagulants or non-vitamin K antagonist oral anticoagulants. These agents include direct thrombin inhibitor and factor Xa inhibitor, and they have been shown to be as good or possibly better than the coumarins with less serious side effects. The newer anticoagulants are more expensive than the traditional ones and should be used in caring for patients with kidney problems.

Coumarins (vitamin K antagonists)

These oral anticoagulants are derived from coumarin found in many plants. A prominent member of this class, warfarin, was found to be the anticoagulant most prescribed in a large multispecialty practice. The anticoagulant effect takes at least 48 to 72 hours to develop. Where an immediate effect is required, heparin is given concomitantly. These anticoagulants are used to treat patients with deep-vein thrombosis and pulmonary embolism and to prevent emboli in patients with atrial fibrillation, and mechanical prosthetic heart valves. Other examples are acenocoumarol, phenprocoumon, atromentin, and phenindione.
The coumarins brodifacoum and difenacoum are used as mammalicides but are not used medically.

Heparin and derivative substances

Heparin is the most widely used intravenous clinical anticoagulant worldwide. Heparin is a naturally occurring glycosaminoglycan. There are three major categories of heparin: unfractionated heparin, low molecular weight heparin, and ultra-low-molecular weight heparin. Unfractionated heparin is usually derived from pig intestines and bovine lungs. UFH binds to the enzyme inhibitor antithrombin III, causing a conformational change that results in its activation. The activated AT then inactivates factor Xa, thrombin, and other coagulation factors. Heparin can be used in vivo, and also in vitro to prevent blood or plasma clotting in or on medical devices. In venipuncture, Vacutainer brand blood collecting tubes containing heparin usually have a green cap.

Low molecular weight heparin (LMWH)

is produced through a controlled depolymerization of unfractionated heparin. LMWH exhibits a higher anti-Xa/anti-IIa activity ratio and is useful as it does not require monitoring of the APTT coagulation parameter and has fewer side effects.