A 12-year-old boy has prolonged oral bleeding immediately after a tooth extraction. Despite several interventions, the bleeding persists for hours and stops only after desmopressin (DDAVP) administration. The patient has several dental caries due to excessive juice intake and inconsistent oral hygiene. He has no other medical problems and takes no medications. His father and paternal grandmother have also had excessive bleeding after dental procedures. Review of systems is positive for mild bruising on his legs. Which of the following is the most likely therapeutic mechanism of desmopressin for this patient's condition?

Question

A 12-year-old boy has prolonged oral bleeding immediately after a tooth extraction.  Despite several interventions, the bleeding persists for hours and stops only after desmopressin (DDAVP) administration.  The patient has several dental caries due to excessive juice intake and inconsistent oral hygiene.  He has no other medical problems and takes no medications.  His father and paternal grandmother have also had excessive bleeding after dental procedures.  Review of systems is positive for mild bruising on his legs.  Which of the following is the most likely therapeutic mechanism of desmopressin for this patient's condition?

Quizplus · Accepted Answer

11ec160b_3bec_5cb9_9249_99f9b68ccef8_MD0001_00 This patient likely has von Willebrand disease (vWD), an autosomal dominant deficiency of von Willebrand factor (vWF). vWF is secreted by endothelial cells and circulates in multimers that are non-covalently attached to clotting factor VIII, increasing its stability. vWF is also responsible for augmenting platelet binding at endothelial injury sites, which helps in the formation of the initial platelet plug. Patients have increased bruisability and mucosal bleeding (eg, oropharyngeal, gastrointestinal, uterine). Common manifestations include prolonged bleeding during dental procedures and heavy menstrual periods. Most patients do not require medical attention as vWD symptoms are typically mild. However, those who need treatment can receive desmopressin (or 1-desamino-8-d-arginine vasopressin [DDAVP]), a synthetic analog of vasopressin (ie, antidiuretic hormone [ADH]), which is normally released by the posterior pituitary. DDAVP increases vWF release from endothelial cells. DDAVP also raises factor VIII levels and is used for the treatment of mild hemophilia A. Hemophilia is an X-linked coagulation disorder and is unlikely in this patient given the clear autosomal dominant pattern of inheritance (father and paternal grandmother). (Choice A) DDAVP also acts as an ADH analogue by binding to V2 receptors in the renal tubular cells, which leads to increased aquaporin channels, increased water reabsorption, and decreased urine output. Due to this action, DDAVP can be used in the treatment of central diabetes insipidus and nocturnal enuresis. (Choice C) Although most clotting factors are synthesized in the liver, vWF and factor VIII are produced in endothelial cells. DDAVP has no known effect on liver protein synthesis. (Choice D) Inhibition of fibrinolysis (breaking down fibrin in blood clots) can decrease the rate of clot breakdown and potentially slow heavy bleeding. Aminocaproic acid is an anti-fibrinolytic medication used to treat excessive postoperative bleeding. DDAVP has no effect on the fibrinolytic system. (Choice E) Vascular smooth muscle cells are involved in blood pressure regulation, with contraction leading to higher blood pressure. Endogenous vasopressin acts via the V1 vasopressin receptor to raise blood pressure through vascular smooth muscle contraction. Although DDAVP is chemically similar to vasopressin, it has a minimal effect on the V1 vasopressin receptor. Educational objective: The von Willebrand factor (vWF) enhances clotting through both augmentation of platelet binding and stabilization of factor VIII. Patients with von Willebrand disease are deficient in functional vWF and present with increased bruisability and prolonged mucosal bleeding. Desmopressin can alleviate bleeding through endothelial release of vWF. __________ References: Desmopressin (DDAVP) in the management of patients with congenital bleeding disorders. (http://www.ncbi.nlm.nih.gov/pubmed/23937614)

A 12-Year-Old Boy Has Prolonged Oral Bleeding Immediately After a Tooth