[1] It arises from a deficiency in the quality or quantity of von Willebrand factor (VWF), a multimeric protein that is required for platelet adhesion.

Deficiency of VWF, therefore, shows primarily in organs with extensive small vessels, such as skin, gastrointestinal tract, and uterus.

In angiodysplasia, a form of telangiectasia of the colon, shear stress is much higher than in average capillaries, and the risk of bleeding is increased concomitantly.

In milder cases of type 1 VWD, a complex spectrum of molecular pathology may exist in addition to polymorphisms of the VWF gene alone.

[15] Basic tests performed in any patient with bleeding problems are a complete blood count-CBC (especially platelet counts), activated partial thromboplastin time-APTT, prothrombin time with International Normalized Ratio-PTINR, thrombin time-TT, and fibrinogen level.

Patients with von Willebrand disease typically display a normal prothrombin time and a variable prolongation of APTT, depending on whether sufficient VWF is available to perform its carrier function for factor VIII.

Normal levels do not exclude all forms of VWD, particularly type 2, which may only be revealed by investigating platelet interaction with subendothelium under flow, a highly specialized coagulation study not routinely performed in most medical laboratories.

Ristocetin-induced platelet agglutination (RIPA), collagen binding, and/or VWF multimer assays may be performed to follow up abnormal screening tests.

To increase the probability of a proper diagnosis, testing should be done at a facility with immediate on-site processing in a specialized coagulation laboratory.

Most cases of low VWF are never diagnosed due to its asymptomatic or mild presentation, and most people with type I VWD end up leading a normal life free of complications, with many being unaware that they have the disorder.

Trouble may, however, arise in some patients in the form of bleeding following surgery (including dental procedures), noticeable easy bruising, or menorrhagia (heavy menstrual periods).

Type 1C VWD indicates patients with quantitative deficiency due to an enhanced VWF clearance, accounting for ~15% to 20% of cases.

[6] The ristocetin cofactor activity is low when the patient's platelet-poor plasma is assayed against formalin-fixed, normal donor platelets.

However, when the assay is performed with the patient's own platelets (platelet-rich plasma), a lower-than-normal amount of ristocetin causes aggregation to occur.

Patients with this subtype are unable to use desmopressin as a treatment for bleeding, because it can lead to unwanted platelet aggregation and aggravation of thrombocytopenia.

Conversely, in VWD Type 2A, high molecular weight multimers are either absent or present in very low quantities.

It occurs in individuals who are homozygous for the defective gene, resulting in a severe quantitative deficiency or complete absence of von Willebrand factor (VWF) production.

The inheritance pattern of VWD type 3 is autosomal recessive, meaning that both parents must carry the defective gene for their child to be affected.

The defect lies in the qualitatively altered GPIb receptor on the platelet membrane which increases its affinity to bind to the VWF.

[27] A form of acquired VWD occurs in patients with aortic valve stenosis, leading to gastrointestinal bleeding (Heyde's syndrome).

Humate P, Alphanate, Wilate and Koate HP are commercially available for prophylaxis and treatment of VWD, and have varying levels of factor VIII.

Recombinant factor VIII products contain insignificant quantity of VWF, so are not clinically useful as standalone therapy for VWD.

[33] Vonicog alfa is a recombinant von Willebrand factor that was approved for use in the United States in December 2015, and for use in the European Union in August 2018.

[38] In 1924, a 5-year-old girl from Föglö, Åland, Finland, was brought to the Deaconess Hospital in Helsinki, where she was seen by Finnish physician Erik Adolf von Willebrand.

He ultimately assessed 66 members of her family and reported in a 1926 Swedish-language article that this was a previously undescribed bleeding disorder that differed from hemophilia.

[40] The eponymous name was assigned to the disease between the late 1930s and the early 1940s, in recognition of von Willebrand's extensive research.

The causal mutation for VWD type 1 was identified in dogs of the breeds Doberman Pinscher, German Pinscher, Bernese Mountain Dog, Manchester Terrier, Kerry Blue Terrier, Cardigan Welsh Corgi, Poodle, Coton de Tulear, Drentse Patrijshond, Papillon, and Stabyhoun.

[44] Mice affected by VWD type 3 were produced by genetic engineering to obtain a small sized model for the human disease.

Deposition of hemosiderin and other blood degradation products on the tooth surfaces turning them brown can occur with continuous oral bleeding over long periods.

The frequency of oral hemorrhage by location in people with deficiency of F VIII and F IX is: gingiva, 64%; dental pulp, 13%; tongue, 7.5%; lip, 7%; palate, 2% and buccal mucosa, 1%.