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Difficulty: EasyHemodynamic and Coagulation Processes

A 68-year-old woman is evaluated in the hospital for a deep vein thrombosis of the left lower extremity. She is prescribed oral warfarin. However, a bridging parenteral anticoagulant is not initiated. Three days later, the patient develops painful, well-demarcated, erythematous lesions on her abdomen and breasts that rapidly progress to purpuric necrosis and eschar formation. This patient's dermatologic complication is most directly caused by a precipitous decline in the plasma activity of which of the following?

  1. Protein CAnswer
  2. B
    Antithrombin
  3. C
    Factor II
  4. D
    Factor VIII
  5. E
    Platelets

Answer

Protein C
The correct answer is Protein C. Warfarin acts by inhibiting the enzyme vitamin K epoxide reductase, which prevents the gamma-carboxylation and activation of vitamin K-dependent clotting factors (II, VII, IX, and X) as well as the endogenous anticoagulant proteins C and S. Because Protein C has a much shorter half-life (approximately 8 hours) compared to the procoagulant factors like Factor II (approximately 60 hours), initiating warfarin without a bridging anticoagulant causes a transient, severe depletion of Protein C while procoagulant factors remain circulating. This imbalance creates a paradoxical hypercoagulable state, leading to microvascular thrombosis and the classic presentation of warfarin-induced skin necrosis.

Step-by-Step Solution

1
Identify the clinical presentation and context.
The patient developed rapid-onset skin necrosis three days after starting warfarin without parenteral bridging.
Recognizing the timeline and medication involved is essential to pinpoint the exact mechanism of the complication.
2
Recall the pharmacological mechanism of warfarin.
Warfarin inhibits vitamin K epoxide reductase, preventing the activation of factors II, VII, IX, X, and proteins C and S.
Understanding which endogenous molecules are affected isolates the potential answers.
3
Differentiate the half-lives of the affected molecules.
Protein C has a much shorter half-life (approximately 8 hours) compared to the procoagulant factors like Factor II (approximately 60 hours).
The differential half-lives explain the transient, paradoxical hypercoagulable state responsible for the microvascular thrombosis and necrosis.

Key Concept

Warfarin-induced skin necrosis due to early depletion of Protein C.
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Topics

Hemodynamic and Coagulation Processes

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