**Core Concept**
Warfarin skin necrosis is a rare but serious side effect of warfarin therapy, occurring due to the interruption of vitamin K-dependent coagulation factors. This condition is characterized by skin necrosis, typically in areas with high adipose tissue.

**Why the Correct Answer is Right**
Warfarin skin necrosis is primarily caused by the paradoxical decrease in protein C levels, which is a vitamin K-dependent anticoagulant protein. Before warfarin takes effect, protein C levels decrease much faster than prothrombin (factor II) levels, leading to a prothrombotic state. This condition is most commonly seen in areas with high adipose tissue, such as the breasts, thighs, and buttocks.

**Why Each Wrong Option is Incorrect**
**Option A:** This option is not relevant to the pathophysiology of warfarin skin necrosis.
**Option B:** Warfarin-induced skin necrosis is not primarily caused by the inhibition of vitamin K-dependent clotting factors, although it is related to their regulation.
**Option C:** This option is incorrect because warfarin skin necrosis is not a result of warfarin's direct toxic effects on skin tissue.

**Clinical Pearl / High-Yield Fact**
Warfarin skin necrosis often occurs within the first week of therapy and is more common in patients with normal to elevated protein C levels. To prevent this condition, it is essential to monitor international normalized ratio (INR) levels closely and consider bridging anticoagulation therapy with heparin in high-risk patients.

**Correct Answer: D. Decrease in protein C levels**