Examkin

Question

Difficulty: MediumHemodynamic and Coagulation Processes

A 23-year-old woman presents to the outpatient clinic with a 3-day history of swelling and a dull ache in her left calf. Her medical history is unremarkable, and she takes no medications other than an oral contraceptive pill that she started three months ago. Vital signs are within normal limits. Physical examination reveals a 3-cm increase in the circumference of the left calf compared to the right, along with localized tenderness along the deep venous system. A comprehensive metabolic panel and complete blood count are within normal limits. Doppler ultrasound confirms an occlusive thrombus in the left popliteal vein. Family history reveals that her maternal aunt developed a pulmonary embolism at age 30 during her first pregnancy. Which of the following best describes the underlying pathophysiologic mechanism of this patient's most likely condition?

  1. Resistance of a procoagulant factor to proteolytic cleavageAnswer
  2. B
    Increased mRNA transcription leading to elevated prothrombin levels
  3. C
    Decreased production of an endogenous serine protease inhibitor
  4. D
    Formation of immunoglobulins directed against phospholipid-binding proteins
  5. E
    Impaired synthesis of a vitamin K-dependent regulatory glycoprotein

Answer

The correct answer is the resistance of a procoagulant factor to proteolytic cleavage, which describes the mechanism of Factor V Leiden.
The patient's presentation of an unprovoked deep vein thrombosis at a young age, exacerbated by oral contraceptive use and accompanied by a strong family history of venous thromboembolism, is classic for an inherited thrombophilia. Factor V Leiden is the most common inherited hypercoagulable state. It is caused by a guanine-to-adenine point mutation in the F5 gene. This mutation substitutes glutamine for arginine at position 506, which alters the normal three-dimensional structure of the factor V protein. Specifically, it eliminates the primary cleavage site where activated protein C (APC) binds to degrade and inactivate factor Va. Because factor Va remains active longer than normal, it continuously acts as a cofactor for factor Xa to convert prothrombin to thrombin, resulting in a prothrombotic state due to resistance to proteolytic cleavage.

Step-by-Step Solution

1
Analyze the patient's demographic, clinical presentation, and risk factors.
A 23-year-old female taking oral contraceptives presents with an unprovoked deep vein thrombosis (DVT).
Identifying the clinical syndrome and acquired risk factors sets the context for an underlying predisposition.
2
Evaluate the family history.
The maternal aunt had a pulmonary embolism at a young age.
A strong family history of venous thromboembolism (VTE) at a young age strongly points to an inherited thrombophilia rather than a purely acquired condition.
3
Identify the most likely underlying condition.
Factor V Leiden is the most common inherited cause of hypercoagulability in Caucasian populations.
When presented with a young patient with an unprovoked VTE and a family history, the most statistically likely inherited defect must be selected.
4
Determine the molecular mechanism of the selected condition.
Factor V Leiden results from a point mutation altering the cleavage site of factor Va.
The mutation prevents activated protein C (APC) from cleaving and inactivating factor Va, leading to a state of resistance to proteolytic cleavage and unchecked coagulation.

Key Concept

Factor V Leiden Pathophysiology
Estimated Time:1m 15s
Rate this question

Topics

Hemodynamic and Coagulation Processes

More questions from this topic