Bleeding The only common side effect of<unk>  is bleeding. The risk of severe bleeding is small but definite (a typical yearly rate of 1–3% has been reported), and any benefit needs to outweigh this risk when<unk>  is considered. All types of bleeding occur more commonly, but the most severe ones are those involving the brain (intracerebral hemorrhage/hemorrhagic stroke) and the spinal cord. Risk of bleeding is increased if the INR is out of range (due to accidental or deliberate overdose or due to interactions). This risk increases greatly once the INR exceeds 4.5. A number of risk scores exist to predict bleeding in people using<unk>  and similar anticoagulants. A commonly used score (HAS-BLED) includes known predictors of<unk> -related bleeding: uncontrolled high blood pressure (H), abnormal kidney function (A), previous stroke (S), known previous bleeding condition (B), previous labile INR when on anticoagulation (L), elderly as defined by age over 65 (E), and drugs associated with bleeding (e.g., aspirin) or alcohol misuse (D). While their use is recommended in clinical practice guidelines, they are only moderately effective in predicting bleeding risk and do not perform well in predicting hemorrhagic stroke. Bleeding risk may be increased in people on hemodialysis. Another score used to assess bleeding risk on anticoagulation, specifically<unk>  or Coumadin, is the ATRIA score, which uses a weighted additive scale of clinical findings to determine bleeding risk stratification. The risks of bleeding are increased further when<unk>  is combined with antiplatelet drugs such as clopidogrel, aspirin, or nonsteroidal anti-inflammatory drugs.<unk>  necrosis A rare but serious complication resulting from treatment with<unk>  is<unk>  necrosis, which occurs more frequently shortly after commencing treatment in patients with a deficiency of protein C. Protein C is an innate anticoagulant that, like the procoagulant factors whose synthesis<unk>  inhibits, requires vitamin K-dependent carboxylation for its activity. Since<unk>  initially decreases protein C levels faster than the coagulation factors, it can paradoxically increase the blood's tendency to coagulate when treatment is first begun (many patients when starting on<unk>  are given heparin in parallel to combat this), leading to massive thrombosis with skin necrosis and gangrene of limbs. Its natural counterpart, purpura fulminans, occurs in children who are homozygous for certain protein C mutations. Osteoporosis After initial reports that<unk>  could reduce bone mineral density, several studies demonstrated a link between<unk>  use and osteoporosis-related fracture. A 1999 study in 572 women taking<unk>  for deep venous thrombosis, risk of vertebral fracture and rib fracture was increased; other fracture types did not occur more commonly. A 2002 study looking at a randomly selected selection of 1,523 patients with osteoporotic fracture found no increased exposure to anticoagulants compared to controls, and neither did stratification of the duration of anticoagulation reveal a trend towards fracture. A 2006 retrospective study of 14,564 Medicare recipients showed that<unk>  use for more than one year was linked with a 60% increased risk of osteoporosis-related fracture in men; there was no association in women. The mechanism was thought to be a combination of reduced intake of vitamin K (a vitamin necessary for bone health) and inhibition by<unk>  of vitamin K-mediated carboxylation of certain bone proteins, rendering them nonfunctional. Purple toe syndrome Another rare complication that may occur early during<unk>  treatment (usually within 3 to 8 weeks of commencement) is purple toe syndrome. This condition is thought to result from small deposits of cholesterol breaking loose and causing embolisms in blood vessels in the skin of the feet, which causes a blueish-purple colour and may be painful. It is typically thought to affect the big toe, but it affects other parts of the feet as well, including the bottom of the foot (plantar surface). The occurrence of purple toe syndrome may require discontinuation of<unk> . Calcification Several studies have also implicated<unk>  use in valvular and vascular calcification. No specific treatment is available, but some modalities are under investigation.
Warfarin
Palladin
Clopidogrel
Ticlopidine
Apixaban
Ticagrelor
Heparin
Dabigatran