vwd can occur in patients with autoantibodies. in this case, the function of vwf is not inhibited, but the vwf-antibody complex is rapidly cleared from the circulation. a form of vwd occurs in patients with aortic valve stenosis, leading to gastrointestinal bleeding (heyde's syndrome). this form of acquired vwd may be more prevalent than is presently thought. in 2003, vincentelli et al. noted that patients with acquired vwd and aortic stenosis who underwent valve replacement experienced a correction of their hemostatic abnormalities, but that the hemostatic abnormalities can recur after 6 months when the prosthetic valve is a poor match with the patient. similarly, acquired vwd contributes to the bleeding tendency in people with an implant of a left ventricular assist device (a pump that pumps blood from the left ventricle of the heart into the aorta). treatment for patients with vwd type 1 and vwd type 2a, desmopressin is available as different preparations, recommended for use in cases of minor trauma, or in preparation for dental or minor surgical procedures. desmopressin stimulates the release of vwf from the weibel–palade bodies of endothelial cells, thereby increasing the levels of vwf (as well as coagulant factor viii) three- to five-fold. desmopressin is also available as a preparation for intranasal administration (stimate) and as a preparation for intravenous administration. desmopressin is contraindicated in vwd type 2b because of the risk of aggravated thrombocytopenia and thrombotic complications. desmopressin is probably not effective in vwd type 2m and is rarely effective in vwd type 2n. it is totally ineffective in vwd type 3. for women with heavy menstrual bleeding, estrogen-containing oral contraceptive medications are effective in reducing the frequency and duration of the menstrual periods. estrogen and progesterone compounds available for use in the correction of menorrhagia are ethinylestradiol and levonorgestrel (levona, nordette, lutera, trivora). administration of ethinylestradiol diminishes the secretion of luteinizing hormone and follicle-stimulating hormone from the pituitary, leading to stabilization of the endometrial surface of the uterus. desmopressin is a synthetic analog of the natural antidiuretic hormone vasopressin. its overuse can lead to water retention and dilutional hyponatremia with consequent convulsion. for patients with vwd scheduled for surgery and cases of vwd disease complicated by clinically significant hemorrhage, human-derived medium purity factor viii concentrates, which also contain von willebrand factors, are available for prophylaxis and treatment. humate p, alphanate, wilate and koate hp are commercially available for prophylaxis and treatment of vwd. monoclonally purified factor viii concentrates and recombinant factor viii concentrates contain insignificant quantity of vwf, so are not clinically useful. development of alloantibodies occurs in 10-15% of patients receiving human-derived medium-purity factor viii concentrates and the risk of allergic reactions including anaphylaxis must be considered when administering these preparations. administration of the latter is also associated with increased risk of venous thromboembolic complications. blood transfusions are given as needed to correct anemia and hypotension secondary to hypovolemia. infusion of platelet concentrates is recommended for correction of hemorrhage associated with platelet-type vwd. 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. epidemiology the prevalence of vwd is about one in 100 individuals. however, the majority of these people do not have symptoms. the prevalence of clinically significant cases is one per 10,000. because most forms are rather mild, they are detected more often in women, whose bleeding tendency shows during menstruation. it may be more severe or apparent in people with blood type o. history 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. he published another article on the disorder in 1931, in the german language, which attracted international attention in the disease. the eponymous name was assigned to the disease between the late 1930s and the early 1940s, in recognition of von willebrand's extensive research. in the 1950s, it became clear that a "plasma factor", factor viii, was decreased in these persons and that cohn fraction i-0 could correct both the plasma deficiency of fviii and the prolonged bleeding time. since this time, the factor causing the long bleeding time was called the "von willebrand factor" in honor of erik adolf von willebrand. variant forms of vwf were recognized in the 1970s, and these variations are now recognized as the result of synthesis of an abnormal protein. during the 1980s, molecular and cellular studies distinguished hemophilia a and vwd more precisely. persons who had vwd had a normal fviii gene on the x chromosome, and some had an abnormal vwf gene on chromosome 12. gene sequencing identified many of these persons as having a vwf gene mutation. the genetic causes of milder forms of low vwf are still under investigation, and these forms may not always be caused by an abnormal vwf gene. other animals vwd can also affect dogs, pigs, and mice. furthermore, cases have been reported in cats, horses, cattle, and rabbits. 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. causal mutations for type 2 were identified in dogs of the breeds german wirehaired pointer, german shorthaired pointer, and chinese crested; and for type 3 in dogs of the breeds kooikerhondje, scottish terrier and shetland sheepdog. in dogs affected by type 1 vwd, the causal mutation was the same across all breeds and the same mutation was also detected in some human vwd type 1 patients. in contrast, the mutations causing vwd type 3 in dogs are specific to each breed. genetic screening is offered for known breeds. in pigs, the causal mutation for vwd type 3 has also been identified. it is a large duplication within the vwf gene and causes serious damage to the gene function, so that virtually no vwf protein is produced. the clinical picture in pigs is most similar to that in humans with vwd type 3. therefore, those pigs are valuable models for clinical and pharmacological research. mice affected by vwd type 3 were produced by genetic engineering to obtain a small sized model for the human disease. in these strains, the vwf gene has been knocked out. in animals of other species affected by vwd, the causal mutations have not yet been identified. oral manifestations in the case of severe deficiency, there may be spontaneous gingival bleeding, ecchymosis, and epistaxis. symptoms of vwd include postoperative bleeding, bleeding after dental extraction, gingival bleeding, epistaxis and easy bruising. the intake of oral contraceptives as the first-line treatment for menorrhagia may lead to gingival enlargement and bleeding in women. platelet or coagulation disorders with severely altered hemostasis can cause spontaneous gingival bleeding, as seen in conjunction with hyperplastic hyperemic gingival enlargements in leukemic patients. 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 location of oral bleeds was as follows: labial frenum, 60%; tongue, 23%; buccal mucosa, 17% and gingiva and palate, 0.5%. severe hemophilia will have most frequent bleeding occurrences, followed by moderate and then mild hemophilia. they mostly come from traumatic injuries. bleeding will also be induced by iatrogenic factors and poor oral hygiene practices. 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%. dental considerations the protocols suggest the use of factor concentrate along with the use of local hemostatic techniques, such as suturing, and local measures, such as the use of oxidized cellulose, for example, surgicel or fibrin glue in conjunction with post-operatively administered antifibrinolytic agents where appropriate. the use of any non-steroidal anti-inflammatory drug (nsaid) must be discussed beforehand with the patient's hematologist because of their effect on platelet aggregation. there are no restrictions regarding the type of local anaesthetic agent used although those with vasoconstrictors may provide additional local hemostasis.