Which of the following is the primary defect in von Willebrand disease type 1?
A. Quantitative deficiency of von Willebrand factor (reduced level of structurally normal vWF)
B. Absence of the largest multimers of von Willebrand factor due to ADAMTS13 deficiency
C. Qualitative defect in von Willebrand factor with normal or near-normal quantity
D. Deficiency of factor VIII with normal von Willebrand factor level
Explanation
Von Willebrand Disease: Classification and Pathophysiology
Key Point
Von Willebrand disease (vWD) is the most common inherited bleeding disorder. Type 1 is characterized by proportionate reduction in both quantity and function of von Willebrand factor (vWF), reflecting a quantitative deficiency.
Classification of von Willebrand Disease
Table
Type
Defect
vWF Level
vWF:RCo/vWF:GPIbM
Factor VIII
Inheritance
Frequency
Type 1
Quantitative (partial deficiency)
↓ (20–80% of normal)
Normal ratio
↓ (parallel to vWF)
Autosomal dominant
~75% of vWD
Type 2
Qualitative (dysfunctional)
Normal/↓
Disproportionately ↓
Normal/↓
Autosomal dominant
~20% of vWD
Type 3
Quantitative (complete deficiency)
Absent (< 3%)
Absent
↓↓ (< 10%)
Autosomal recessive
~5% of vWD
Type 2N
Defective Factor VIII binding
Normal/↓
Normal
↓↓
Autosomal recessive
Rare
Mnemonic
"Type 1 = Proportionate" — In type 1 vWD, vWF antigen (vWF:Ag), ristocetin cofactor activity (vWF:RCo), and Factor VIII all decrease proportionally. The ratio vWF:RCo/vWF:Ag remains ≥ 0.6 (normal).
Type 1 vWD: Pathophysiology
1.
Quantitative deficiency — Reduced synthesis or increased clearance of structurally normal vWF
2.
Proportional reduction — Both vWF:Ag and vWF:RCo are reduced equally
3.
Secondary Factor VIII deficiency — Because vWF stabilizes Factor VIII, low vWF → low Factor VIII
Autosomal dominant inheritance — Heterozygous carriers; homozygotes are rare
High-YieldNEET PG
Type 1 vWD is often missed or underdiagnosed because:
vWF levels fluctuate with stress, exercise, estrogen, and blood type (type O individuals have 25–30% lower vWF)
Mild symptoms may be attributed to other causes
Diagnosis requires serial testing on different occasions
Clinical Pearl
In type 1 vWD, desmopressin (DDAVP) is the first-line treatment because it stimulates endothelial cells to release stored vWF, raising levels 2–3 fold. This works in type 1 (where vWF is present but reduced) but NOT in type 3 (where vWF is absent).
Contrast with Type 2 vWD
In type 2 vWD (qualitative defect), vWF:RCo is disproportionately reduced compared to vWF:Ag, giving a ratio < 0.6. This indicates dysfunctional vWF that is present but does not bind platelets normally.
Harrison 21e Ch 181; Robbins 10e Ch 4
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