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Von Willebrand disease

Background

Overview

Definition
vWD is an inherited bleeding disorder that results in defective platelet adhesion and aggregation.
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Pathophysiology
In most cases, vWD results from a mutation in the gene coding for vWF, a key glycoprotein in both primary and secondary hemostasis. Mutations may lead to a quantitative deficiency of vWF (70-80%), dysfunction of vWF (20%), or absence of vWF (< 5%).
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Epidemiology
Laboratory-defined vWD affects approximately 1% of the population. However, the symptomatic prevalence is estimated at 10 persons per 100,000 population.
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Disease course
Clinical manifestations of abnormal hemostasis may include epistaxis, bleeding from minor wounds, hematomas, menorrhagia, postpartum hemorrhage, increased bleeding after surgery or dental extractions, intra-articular bleeding and life-threatening gastrointestinal bleeding from angiodysplasia.
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Prognosis and risk of recurrence
Most patients with vWD have mild bleeding and require only episodic treatment. Women with vWD may have a higher risk of postpartum hemorrhage and peripartum mortality.
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Guidelines

Key sources

The following summarized guidelines for the evaluation and management of von Willebrand disease are prepared by our editorial team based on guidelines from the National Hemophilia Foundation (NHF/ISTH/WFH/ASH 2021) and the British Society for Haematology (BSH 2014).
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Screening and diagnosis

Indications for screening: as per ASH/ISTH/NHF/WFH 2021 guidelines, use a validated bleeding assessment tool as an initial screening test to determine patients requiring specific blood testing in patients with a low probability of vWD (such as seen in the primary care setting).
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  • Screening of family relatives

  • Diagnostic criteria

Diagnostic investigations

Clinical history: as per BSH 2014 guidelines, use a bleeding score (e.g. Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis bleeding assessment tool) to standardize history taking.
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  • Initial laboratory tests

  • Additional laboratory tests

  • Ristocetin-induced platelet aggregation testing

  • Multimer analysis

  • Genetic testing

Medical management

Desmopressin trial: as per ASH/ISTH/NHF/WFH 2021 guidelines, consider administering a trial of desmopressin and treating based on the results in patients with baseline vWF level of < 0.30 IU/mL, if desmopressin is a valid treatment option (primarily type 1 vWD). Avoid initiating desmopressin in the absence of desmopressin trial results in these patients.
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  • Management of acute bleeding

  • Prevention of recurrent bleeding

  • Antithrombotic therapy

Perioperative care

Perioperative care: as per ASH/ISTH/NHF/WFH 2021 guidelines, consider targeting both FVIII and vWF activity levels of ≥ 0.50 IU/mL for at least 3 days after major surgery. Avoid using only FVIII ≥ 0.50 IU/mL as a target level for at least 3 days after surgery.
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Specific circumstances

Pregnant patients: as per ASH/ISTH/NHF/WFH 2021 guidelines, avoid using desmopressin in patients with preeclampsia and with CVD.
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  • Patients with heavy menstrual bleeding

Patient education

General counseling
As per ASH/ISTH/NHF/WFH 2021 guidelines:
Counsel patients about desmopressin therapy including strategies to mitigate risks associated with hyponatremia (such as free water restriction and education about signs and symptoms of hyponatremia that should lead to prompt medical evaluation) and CVD.
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Educate patients about the risks and benefits of using antiplatelet agents or anticoagulant therapy to inform shared decision-making.
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