Differences Between Type 2 von Willebrand Disease and Factor XIII Deficiency
Type 2 von Willebrand disease and Factor XIII deficiency are distinct bleeding disorders with different pathophysiologies, clinical presentations, laboratory findings, and treatment approaches.
Pathophysiology
Type 2 von Willebrand Disease
- Qualitative defect in von Willebrand factor (VWF) structure or function 1
- VWF is a multimeric plasma glycoprotein with dual roles:
- Mediates platelet adhesion and aggregation (primary hemostasis)
- Carries and stabilizes Factor VIII (secondary hemostasis) 1
- Further subdivided into subtypes (2A, 2B, 2M, 2N) based on specific functional abnormalities 2
- Predominantly inherited in an autosomal dominant pattern 1
Factor XIII Deficiency
- Deficiency of Factor XIII, which stabilizes fibrin clots by cross-linking fibrin molecules
- Much rarer than VWD (prevalence approximately 1/2 million) 3
- Autosomal recessive inheritance 3
Clinical Presentation
Type 2 von Willebrand Disease
- Primarily mucocutaneous bleeding:
- Nosebleeds
- Easy bruising
- Gingival bleeding
- Bleeding from small wounds
- Menorrhagia in women 1
- Intracranial hemorrhage (ICH) is extremely rare 3
- Some subtypes (2B) may present with thrombocytopenia 1
Factor XIII Deficiency
- More severe bleeding phenotype
- High rate (33%) of intracranial hemorrhage 3
- Delayed bleeding is characteristic (occurs hours to days after injury)
- Poor wound healing and recurrent miscarriages in women
- Umbilical cord bleeding in newborns
Laboratory Findings
Type 2 von Willebrand Disease
- Normal Prothrombin Time (PT) 1
- Normal or mildly prolonged Activated Partial Thromboplastin Time (aPTT) 1
- Disproportionately low VWF activity (VWF:RCo) relative to VWF antigen (VWF:Ag) 2
- Abnormal VWF multimer pattern depending on subtype:
- Type 2A and 2B: Absence of high molecular weight multimers
- Type 2M: Normal multimer pattern but decreased function
- Type 2N: Normal multimers but decreased FVIII binding 2
Factor XIII Deficiency
- Normal PT and aPTT (standard coagulation tests are typically normal) 3
- Positive clot solubility test in 5M urea 4
- Specific Factor XIII activity assays show decreased levels
Treatment Approaches
Type 2 von Willebrand Disease
- Desmopressin is generally not effective in Type 2 VWD (except in specific subtypes after documented response testing) 1
- VWF/FVIII concentrates are the primary treatment 1, 5
- Antifibrinolytic agents and hormone therapy as adjunctive treatments 1
Factor XIII Deficiency
- Factor XIII concentrate is the treatment of choice
- Prophylaxis is often recommended due to high risk of spontaneous life-threatening bleeds, especially ICH 3
- Fresh frozen plasma can be used if concentrate unavailable
Key Distinguishing Features
Prevalence: VWD is much more common (up to 1% of population) vs. Factor XIII deficiency (1/2 million) 3, 1
Bleeding Pattern:
- VWD: Predominantly mucocutaneous bleeding
- Factor XIII: Higher risk of deep tissue bleeding, ICH, and delayed bleeding
Laboratory Diagnosis:
- VWD: Abnormal VWF tests (VWF:Ag, VWF:RCo)
- Factor XIII: Normal basic coagulation tests but positive clot solubility test
Risk of ICH:
- VWD: Extremely rare
- Factor XIII deficiency: High risk (33%) 3
Treatment Response:
- Type 2 VWD: Generally requires VWF concentrates
- Factor XIII deficiency: Requires specific Factor XIII replacement
Clinical Pitfalls to Avoid
- Don't rely solely on basic coagulation tests (PT/aPTT) as they may be normal in both conditions 3, 1
- Don't assume all bleeding disorders present with immediate bleeding; Factor XIII deficiency characteristically presents with delayed bleeding
- Don't use desmopressin as first-line therapy for Type 2 VWD without documented response testing 1
- Remember that VWF is an acute phase reactant and levels can be falsely elevated during stress or inflammation, requiring repeat testing 3
- Consider that these disorders can rarely occur together, as reported in literature 4