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Difficulty: HardFormulating a Differential Diagnosis

A 28-year-old woman presents to the outpatient clinic for evaluation of easy bruising and heavy menstrual bleeding over the past six months. She reports that her menses now last for 8 days and require changing a super-absorbent pad every 2 hours during the heaviest days. Two weeks ago, she underwent a dental extraction that was complicated by persistent bleeding requiring packing and tranexamic acid mouthwash. She has no chronic medical conditions and takes no daily medications, though she occasionally uses ibuprofen for menstrual cramps. Family history is notable for her mother having a "bleeding problem" after childbirth.

Vital signs are within normal limits. Physical examination reveals scattered ecchymoses on her bilateral lower extremities, measuring up to 3 cm in diameter. There is no hepatosplenomegaly, joint swelling, or deformity.

Laboratory evaluation reveals the following:

Laboratory TestResultReference Range
Hemoglobin11.2 g/dL12.0 - 16.0 g/dL
Mean corpuscular volume78 fL80 - 100 fL
Platelet count240,000/µL150,000 - 400,000/µL
Prothrombin time (PT)12 seconds11 - 15 seconds
Activated partial thromboplastin time (aPTT)46 seconds25 - 40 seconds
Bleeding time10 minutes2 - 7 minutes

A mixing study is performed, and the patient's aPTT corrects to 32 seconds when mixed 1:1 with normal pooled plasma.

Which of the following is the most likely diagnosis in this patient?

  1. A
    Immune thrombocytopenic purpura
  2. B
    Hemophilia A
  3. von Willebrand diseaseAnswer
  4. D
    Antiphospholipid syndrome
  5. E
    NSAID-induced platelet dysfunction

Answer

von Willebrand disease
The correct answer is von Willebrand disease (vWD), the most common inherited bleeding disorder. vWD is caused by a quantitative or qualitative deficiency of von Willebrand factor (vWF). vWF serves two critical hemostatic roles: it bridges platelets to exposed subendothelial collagen (facilitating primary hemostasis) and it acts as a carrier protein for Factor VIII, protecting it from rapid proteolytic degradation (facilitating secondary hemostasis). Consequently, patients with vWD typically present with mucocutaneous bleeding, such as menorrhagia, epistaxis, or excessive bleeding following minor surgical procedures (e.g., dental extractions). Laboratory evaluation classically demonstrates a prolonged bleeding time (or prolonged PFA-100 closure time) due to the primary hemostasis defect, and a prolonged aPTT due to the secondary decline in Factor VIII levels. Because this represents a true factor deficiency, the aPTT will correct when the patient's plasma is mixed with normal pooled plasma.

Step-by-Step Solution

1
Analyze the patient's clinical presentation and demographic profile.
A young woman with a history of mucocutaneous bleeding (heavy menses, prolonged bleeding after extraction) and a family history of bleeding issues.
To establish the primary clinical syndrome, which strongly points toward an inherited defect in primary hemostasis.
2
Interpret the basic coagulation panel and complete blood count.
The platelet count and PT are normal, but both the aPTT and the bleeding time are prolonged.
To categorize the hemostatic defect. The prolonged bleeding time confirms a primary hemostasis defect, while the prolonged aPTT indicates a concurrent secondary hemostasis issue within the intrinsic pathway.
3
Interpret the results of the mixing study.
The prolonged aPTT completely corrects upon 1:1 mixing with normal pooled plasma.
To differentiate between a coagulation factor deficiency (which corrects upon mixing) and the presence of an inhibitor (which does not correct).
4
Synthesize the findings to formulate the most likely differential diagnosis.
A combined defect of primary hemostasis (platelet function) and a specific factor deficiency (intrinsic pathway) is most consistent with von Willebrand disease.
von Willebrand factor is uniquely responsible for both mediating platelet adhesion and stabilizing Factor VIII in the plasma.

Key Concept

von Willebrand disease presents with both primary and secondary hemostatic defects due to impaired platelet adhesion and a decreased half-life of Factor VIII, leading to a prolonged bleeding time and a prolonged aPTT that corrects on a mixing study.
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Topics

Formulating a Differential Diagnosis

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