OOA (Old Order Amish)

Inheritance: autosomal recessive, autosomal dominant
Genes: VFW

VMD
Von Willebrand factor deficiency
Factor VIII-von Willebrand factor
F8VWF

Hemorrhage
Bleeding
Factor VIII
Von Willebrand factor
Platelet defect

von Willebrand Disease

Clinical Characteristics

General description (for patients):

Von Willebrand disease is a hereditary bleeding disorder.  Many subtypes are known but the defect in all involves the inability for platelets in the blood to plug holes in ruptured blood vessels.  Thus, bleeding following trauma is prolonged.  Nosebleeds, easy bruising, and troublesome bleeding following tooth extractions or minor cuts are symptoms.

Medical description:  

The primary clotting problem in this disorder is due to limited platelet aggregation and clot retraction caused by a genetic defect in von Willebrand factor.  Hence, bleeding time is prolonged, often complicating minor trauma or dental extractions.  Easy bruising and prolonged epistaxis are often features as well.  Transfusions of normal plasma have an extended beneficial effect, longer than in hemophilia.  Factor VIII levels are severely reduced and a VIII-rich cryoprecipitate can have the same therapeutic effect.

Genetics:

The von Willebrand factor gene (VFW) is located on chromosome 12 (12p13.3).  Many mutations and variants have been described.  A large Amish kindred with Type 2M disease (4120C>T) has been reported in the Midwest.  Both autosomal dominant and recessive inheritance exist, with the majority of cases (including the Amish kindred) following the former pattern.

Treatment:

Transfusions of whole blood and of factor VIII-rich cryoprecipitates have a prolonged beneficial effect. Intranasal desmopressin (DDAVP) (Stimate) and subcutaneous administration can be temporarily helpful as well, albeit with limited protection for major bleeding or invasive surgical procedures.

Prognosis:

Excellent longevity with appropriate interventional treatment as required.

Ancillary treatments and support:

Avoidance of major trauma and prophylactic infusions (such as Humate-P) prior to major surgical procedures.

Specialists and specialty centers:

Hematologist.

References:

Sharthkumar, A, Greit, A., Di Paola, J., Winay, J., Roberson, C., Heiman, M.,  Herbert, S., Parameswaran, R., and Shapiro, A.:  Biologic response to subcutaneous and intranasal therapy with desmopressin in a large Amish kindred with Type 2M von Willebrand disease.  Haemophilia 14: 539-548, 2008.  PubMed ID: 18312368

Mannucci, P.M.:  Treatment of von Willebrand’s disease.  New Eng. J. Med. 351: 683-694, 2004.  PubMed ID: 15306670

Federici, A.B., and Mannucci, P.M.:  Management of inherited von Willebrand disease in 2007.  Ann. Med. 39: 346-358, 2007.  PubMed ID: 17701477

Resources:

National Hemophilia Foundation
All About Bleeding

Associated Graphics