The coagulation cascade.<unk>  usually occurs three to five days after drug therapy is begun, and a high initial dose increases the risk of its development.<unk> -induced<unk>  can develop both at sites of local injection and - when infused intravenously - in a widespread pattern. In<unk> 's initial stages of action, inhibition of protein C and Factor VII is stronger than inhibition of the other vitamin K-dependent coagulation factors II, IX, and X. This results from the fact that these proteins have different half-lives: 1.5 to six hours for factor VII and eight hours for protein C, versus one day for factor IX, two days for factor X and two to five days for factor II. The larger the initial dose of vitamin K-antagonist, the more pronounced these differences are. This coagulation factor imbalance leads to paradoxical activation of coagulation, resulting in a hypercoagulable state and thrombosis. The blood clots interrupt the blood supply to the skin, causing<unk> . Protein C is an innate anticoagulant, and as<unk>  further decreases protein C levels, it can lead to massive thrombosis with<unk>  and gangrene of limbs. Notably, the prothrombin time (or international normalized ratio, INR) used to test the effect of<unk>  is highly dependent on factor VII, which explains why patients can have a therapeutic INR (indicating good anticoagulant effect) but still be in a hypercoagulable state. In one third of cases,<unk>  occurs in patients with an underlying, innate and previously unknown deficiency of protein C. The condition is related to purpura fulminans, a complication in infants with sepsis which also involves skin<unk> . These infants often have protein C deficiency as well. There have also been cases in patients with other deficiency, including protein S deficiency, activated protein C resistance (Factor V Leiden) and antithrombin III deficiency. Although the above hypothesis is the most commonly accepted, others believe that it is a hypersensitivity reaction or a direct toxic effect.
Warfarin necrosis
Fibrinolysis syndrome
Anemic infarct
Reperfusion injury
Coronary steal
Post-thrombotic syndrome
Gas gangrene
Ischemia