Anticoagulant

Anticoagulants, often called blood thinners, are substances that slow down or stop blood from clotting, which extends the time it takes for a clot to form. Some of these occur naturally in animals that feed on blood, like leeches and mosquitoes, allowing their bites to stay open and unclotted long enough for them to feed. As a group of drugs, anticoagulants are used to treat conditions involving unwanted blood clots. They work by interfering with specific steps in the coagulation cascade—the chain of events that happens after platelets first clump together, before fibrin and stable clots form. This sets them apart from antiplatelet drugs, which stop platelets from clumping, and thrombolytic drugs, which break up existing clots. Common examples include warfarin and heparin. Warfarin was originally approved as a rat poison before becoming a medical treatment.

Deciding to use anticoagulants involves weighing the benefits against the risks. The main risk is increased bleeding. For healthy people, this risk is small, but it can be too high for those who have recently had surgery, have cerebral aneurysms, or other conditions. The benefit is preventing or slowing the progression of thromboembolic diseases. Conditions where anticoagulation is known to help include atrial fibrillation (which often creates clots in the heart’s atrial appendage), coronary artery disease, deep vein thrombosis (which can lead to a pulmonary embolism), ischemic stroke, hypercoagulable states like Factor V Leiden, mechanical heart valves, myocardial infarction, pulmonary embolism, restenosis from stents, cardiopulmonary bypass or other surgeries requiring temporary aortic occlusion, and heart failure. In these cases, the therapy stops dangerous clots from forming or growing. Doctors often use bleeding risk tools like HAS-BLED, ATRIA, HEMORR2HAGES, and CHA2DS2-VASc to assess the risk of bleeding before starting treatment, then compare that risk to the risk of clotting to decide if the therapy is worthwhile. For people with cerebral small vessel disease who do not have dementia, adding anticoagulants to standard care does not appear to help and raises the chance of bleeding.

The most common and serious side effects of anticoagulants are bleeding events, both minor and major. How likely bleeding is depends on the specific drug, the patient’s age, and their other health conditions. Warfarin causes bleeding in about 15–20% of patients per year, with life-threatening bleeding in 1–3% per year. Newer non-vitamin K antagonist oral anticoagulants seem to cause fewer life-threatening bleeds than warfarin. Patients aged 80 or older are especially vulnerable, with about 13 bleeds per 100 person-years. Bleeding risk is particularly important for patients with kidney problems taking NOACs, since these drugs are partly cleared by the kidneys. In people with cancer, one review found that warfarin did not lower death rates or the risk of clots, but it did increase major bleeding by 107 cases per 1,000 people and minor bleeding by 167 per 1,000. Apixaban, based on a single study, had no effect on death, clot recurrence, or major or minor bleeding.

Non-bleeding side effects are less common but still need monitoring. Warfarin can cause skin necrosis, limb gangrene, and purple toe syndrome. Skin necrosis and limb gangrene usually appear three to eight days after starting treatment, likely because warfarin blocks the production of proteins C and S. Purple toe syndrome typically develops three to eight weeks after starting warfarin. Warfarin also depletes vitamin K, which can interfere with G1a proteins and growth arrest-specific gene 6, raising the risk of arterial calcification and heart valve problems, especially if too much vitamin D is present. This interference with G1a proteins has also been linked to abnormal fetal bone development in pregnant women treated with warfarin. Long-term use of warfarin and heparin is associated with osteoporosis. Another serious complication from heparin is heparin-induced thrombocytopenia (HIT), which comes in two types: immune-mediated and non-immune-mediated. Immune-mediated HIT usually appears five to ten days after starting heparin, and it is thought to be caused by heparin-dependent antibodies.