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 warfarin 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 warfarin is combined with antiplatelet drugs such as clopidogrel, aspirin, or nonsteroidal anti-inflammatory drugs. warfarin necrosis main article: warfarin necrosis a rare but serious complication resulting from treatment with warfarin is warfarin necrosis, which occurs more frequently shortly after commencing treatment in patients with a deficiency of protein c, an innate anticoagulant that, like the procoagulant factors whose synthesis warfarin inhibits, requires vitamin k-dependent carboxylation for its activity. since warfarin 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 warfarin 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 warfarin could reduce bone mineral density, several studies demonstrated a link between warfarin use and osteoporosis-related fracture. a 1999 study in 572 women taking warfarin 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 warfarin use for more than one year was linked with a 60% increased risk of osteoporosis-related fracture in men, but no association in women was seen. the mechanism was thought to be a combination of reduced intake of vitamin k (a vitamin necessary for bone health) and inhibition by warfarin of vitamin k-mediated carboxylation of certain bone proteins, rendering them nonfunctional. purple toe syndrome