Von Willebrand Disease Type 3
Based on the laboratory values provided (VWF:Ag 19%, VWF activity 17%, and Factor VIII 47%), this patient has von Willebrand disease Type 3. 1, 2, 3
Diagnostic Reasoning
The classification is determined by analyzing the pattern of all three test results together:
VWF:Ag of 19% is severely reduced (normal range 50-200 IU/dL), indicating a profound quantitative deficiency of von Willebrand factor protein 1, 2
VWF activity (ristocetin cofactor) of 17% is severely reduced and proportionally matches the VWF:Ag level, confirming this is a quantitative rather than qualitative defect 1, 2
The VWF:RCo/VWF:Ag ratio is approximately 0.89 (17/19), which is >0.7, indicating the von Willebrand factor that is present functions normally - this rules out Type 2 variants 2, 4
Factor VIII activity of 47% is moderately reduced but not as severely as the VWF levels, which is characteristic of Type 3 VWD where some Factor VIII activity is preserved despite near-absent VWF 1, 3
Type 3 VWD Characteristics
Type 3 represents the most severe form of von Willebrand disease:
VWF:RCo levels <30 IU/dL establish a definitive diagnosis of VWD, and levels this low (17%) are consistent with Type 3 2
Type 3 VWD is caused by homozygosity or compound heterozygosity for null mutations in the VWF gene, resulting in virtually absent VWF protein 3
Factor VIII levels are typically reduced to 5-20% in Type 3, though this patient's level of 47% is higher than typical - this may represent a severe Type 1 rather than true Type 3, but the extremely low VWF levels favor Type 3 3
Distinguishing from Type 1
The distinction between severe Type 1 and Type 3 can be nuanced:
Type 1 VWD shows proportionally low VWF:Ag, VWF:RCo, and Factor VIII with normal VWF:RCo/VWF:Ag ratios (>0.5-0.7), similar to this patient 2, 4
However, VWF levels <20% typically indicate Type 3 rather than Type 1, making Type 3 the most likely diagnosis here 2, 3
The relatively preserved Factor VIII at 47% is unusual for Type 3 but can occur, and may suggest this represents the severe end of Type 1 or a mild Type 3 3
Confirmatory Testing Needed
Additional specialized testing should be performed:
VWF multimer analysis is essential to confirm the diagnosis - Type 3 shows absent or barely detectable multimers, while severe Type 1 shows all multimers present but in reduced amounts 2, 3
Genetic testing of the VWF gene can identify homozygous or compound heterozygous null mutations confirming Type 3, versus missense mutations suggesting severe Type 1 3
DDAVP challenge testing will show no response in Type 3 (very poor or non-responsive) versus potential partial response in severe Type 1 3
Critical Management Implications
The distinction between Type 3 and severe Type 1 has major therapeutic consequences:
Type 3 patients require VWF/Factor VIII concentrate replacement therapy for bleeding episodes and surgical prophylaxis, as DDAVP will be ineffective 3
Referral to a hemostasis specialist is mandatory for patients with VWF:RCo <30 IU/dL to guide subtyping, genetic counseling, and treatment planning 2
These patients are at high risk for severe bleeding including joint and muscle hemorrhages similar to hemophilia, requiring comprehensive bleeding disorder management 3