Deficiency of vWF, cause mixed platelet and coagulation disorders

Epidemiology

Most common congenital bleeding disorder.

Etiology

Lymphoproliferative and myeloproliferative diseases (e.g., multiple myeloma, monoclonal gammopathies, lymphoma, essential thrombocythemia)
Autoimmune diseases (e.g., SLE)
Cardiovascular defects (e.g., ventricular septal defect, aortic stenosis)
- These conditions lead to increased shear stress in blood vessel which can result in increased degradation of vWF.
Hypothyroidism
Side effects of certain drugs (e.g., valproic acid)

Von Willebrand factor (vWF): plasma protein that is synthesized by and stored in endothelial cells (in Weibel-Palade bodies) and platelets (in α-granules)
- Mediates platelet adhesion and aggregation
- Binds factor VIII (and thereby prevents its degradation)

Deficiency or dysfunction of vWF leads to:

Dysfunctional platelet adhesion → impaired primary hemostasis
Reduced binding of factor VIII → increased degradation → ↓ factor VIII activity → impaired intrinsic pathway of secondary hemostasis

Predominantly mucocutaneous bleeding.
Common Sx: Epistaxis (nosebleeds), gingival bleeding, easy bruising, petechiae.
Menorrhagia (heavy menstrual bleeding) is very common in female pts.
Prolonged bleeding after minor cuts, dental procedures, or surgery.
Severe forms (Type 3) can present similarly to hemophilia with hemarthrosis (joint bleeding) and soft tissue hematomas.

Platelet Count: Normal. The defect is in platelet function (adhesion), not number.
Bleeding Time: Increased due to impaired platelet plug formation.
Prothrombin Time (PT): Normal, as the extrinsic pathway is unaffected.
Partial Thromboplastin Time (PTT): Normal or Increased. PTT may be elevated because ↓ vWF leads to ↓ Factor VIII levels.
- The PTT test is relatively insensitive to mild deficiencies of clotting factors. For the PTT to become prolonged, Factor VIII activity must typically drop below 30-40% of normal.
Definitive Tests:
- Ristocetin Cofactor Assay: This is the key functional test. It measures vWF’s ability to agglutinate platelets in the presence of the antibiotic ristocetin. In vWD, there is ↓ or absent agglutination. This test is abnormal in all types except 2N.
- vWF Antigen: Measures the quantity of vWF protein.
- Factor VIII Activity: Often decreased.

Desmopressin (DDAVP): stimulates vWF release from endothelial cells
- Best initial treatment for mild or moderate symptoms (typically type 1 and, sometimes, type 2)
- Not effective for type 3
- Has a minimal effect on the V1 vasopressin receptor. Therefore won’t cause vasoconstriction.
Concentrates containing vWF and factor VIII: indicated for severe bleeding, as prophylaxis for surgical procedures and if DDAVP treatment is ineffective