For people who need rapid reversal of warfarin – such as due to serious bleeding – or who need emergency surgery, the effects of warfarin can be reversed with vitamin K, prothrombin complex concentrate (PCC), or fresh frozen plasma (FFP) Generally, four-factor PCC can be given more quickly than FFP, the amount needed is a smaller volume of fluid than FFP, and does not require ABO blood typing. Administration of PCCs results in rapid hemostasis, similar to that of FFP, namely, with comparable rates of thromboembolic events, but with reduced rates of volume overload. Blood products should not be routinely used to reverse warfarin overdose, when vitamin K could work alone. While PCC has been found in lab tests to be better than FFP, when rapid reversal is needed, as of 2018, whether a difference in outcomes such as death or disability exists is unclear.When warfarin is being given and INR is in therapeutic range, simple discontinuation of the drug for five days is usually enough to reverse the effect and cause INR to drop below 1.5. Interactions
Warfarin interacts with many commonly used drugs, and the metabolism of warfarin varies greatly between patients. Some foods have also been reported to interact with warfarin. Apart from the metabolic interactions, highly protein bound drugs can displace warfarin from serum albumin and cause an increase in the INR.
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 bloods 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.