Von Willebrand Disease

VWD usually produces mucocutaneous bleeding, including epistaxis, oral bleeding, heavy menstrual bleeding, and excess bleeding after trauma or surgery. Postpartum hemorrhage is a recurrent high-risk setting. Hemarthrosis is uncommon and should prompt consideration of severe VWD, especially type 3 disease, or an alternative coagulation disorder. BMJBMJVon Willebrand disease - Symptoms, diagnosis and treatment | BMJ Best Practice US

For serious or life-threatening bleeding, use a VWF-containing product rather than desmopressin because the desmopressin-induced rise in VWF is transient and may not provide adequate hemostasis. U.S.-approved plasma-derived VWF products include Humate-P, Alphanate, and Wilate; these products contain both VWF and factor VIII in differing ratios. ccjmccjmvon Willebrand disease: A guide for the internist | Cleveland Clinic Journal of medicine

Use tranexamic acid for mucosal bleeding when not contraindicated; it can be administered orally, intravenously, or as mouthwash and can be combined with desmopressin or VWF-containing products. Avoid antifibrinolytic therapy in patients with significant hematuria because clot retention can obstruct the urinary tract, and avoid it in patients with prior thromboembolic disease. ccjmccjmvon Willebrand disease: A guide for the internist | Cleveland Clinic Journal of medicine

Obtain a structured personal bleeding history and family bleeding history, then measure VWF antigen (VWF:Ag), platelet-binding VWF activity, and factor VIII activity (FVIII:C). VWF activity assays include ristocetin cofactor activity (VWF:RCo), recombinant GPIb assays with ristocetin (VWF:GPIbR), and gain-of-function recombinant GPIb assays without ristocetin (VWF:GPIbM). Collagen-binding activity (VWF:CB) evaluates a separate functional interaction. Wiley+2WileyClassification of von Willebrand disease in the context of modern contemporary von Willebrand factor testing methodologies - Favaloro - 2020 - Research and Practice in Thrombosis and Haemostasis - Wiley Online LibraryWileyEstablishment and characterization of a new and stable collagen‐binding assay for the assessment of von Willebrand factor activity - Ni - 2013 - International Journal of Laboratory Hematology - Wiley Online LibraryScienceDirectDiagnosis of von Willebrand disease

PT, aPTT, platelet count, and bleeding time do not establish or exclude VWD. In a comparative pediatric series, bleeding time was abnormal in only 43% of affected patients; diagnosis instead required a compatible personal and family bleeding history plus an abnormal VWF activity or antigen result. PubMedPubMedRelative value of diagnostic studies for von Willebrand disease - PubMed

Interpret low VWF measurements in the context of the bleeding phenotype and repeated laboratory assessment. VWF values from 0.30 to 0.60 IU/mL can be associated with bleeding, whereas a baseline VWF activity below 0.30 IU/mL is a threshold specifically used by the management guideline to support a desmopressin trial when that agent is a potential treatment option. BMJ+1BMJguided dosing of desmopressin and von Willebrand factor - BMJ OpenASHASH ISTH NHF WFH 2021 guidelines on the management of von Willebrand disease | Blood Advances | American Society of Hematology

Desmopressin is primarily a treatment option for type 1 VWD. For patients with baseline VWF below 0.30 IU/mL in whom desmopressin is otherwise appropriate, perform a trial and use the measured response to guide therapy rather than treating empirically with tranexamic acid or factor concentrate. ASHASHASH ISTH NHF WFH 2021 guidelines on the management of von Willebrand disease | Blood Advances | American Society of Hematology

Do not extrapolate a desmopressin response across all VWD phenotypes. Large interpatient differences in desmopressin response occur, and pharmacokinetics of both desmopressin and VWF-containing concentrates vary within and between patients. Record the peak and duration of VWF activity and FVIII response from the trial in the chart available to procedural and obstetric teams. BMJBMJIs pharmacokinetic-guided dosing of desmopressin and von Willebrand factor-containing concentrates in individuals with von Willebrand disease or low von Willebrand factor reliable and feasible? A protocol for a multicentre, non-randomised, open label cohort trial, the OPTI-CLOT: to WiN study

Monitor for hyponatremia, headache, vasodilation, hypotension, tachycardia, flushing, and rare thrombosis during desmopressin use. Tachyphylaxis can develop within days because endothelial VWF stores become depleted; repeated use should therefore not substitute for factor replacement when sustained hemostatic levels are required. ccjmccjmvon Willebrand disease: A guide for the internist | Cleveland Clinic Journal of medicine

For minor surgery or a minor invasive procedure, the guideline suggests raising VWF activity to at least 0.50 IU/mL with desmopressin or factor concentrate and adding tranexamic acid rather than using desmopressin or factor concentrate alone. This strategy applies when a hemostatic VWF increase is needed and should be individualized by procedure site, bleeding history, and prior treatment response. ASHASHASH ISTH NHF WFH 2021 guidelines on the management of von Willebrand disease | Blood Advances | American Society of Hematology

For patients with type 1 VWD, baseline VWF activity above 0.30 IU/mL, and a mild bleeding phenotype who are undergoing a minor mucosal procedure, tranexamic acid alone is suggested over actively raising VWF activity to at least 0.50 IU/mL. This exception should not be extended to severe phenotypes, major surgery, or patients without a reliable prior assessment of bleeding risk. ASHASHASH ISTH NHF WFH 2021 guidelines on the management of von Willebrand disease | Blood Advances | American Society of Hematology

Major surgery requires planned VWF and FVIII monitoring. A cited Dutch perioperative framework targets FVIII:C and VWF activity above 0.80 IU/mL before surgery and 36 hours postoperatively, then FVIII:C above 0.50 IU/mL for 7 to 10 days after major surgery; these values illustrate the need for sustained postoperative factor management rather than a single preoperative dose. BMJBMJguided dosing of desmopressin and von Willebrand factor - BMJ Open

Heavy menstrual bleeding and postpartum hemorrhage are common VWD manifestations. Tranexamic acid is particularly useful for menstrual and postpartum mucosal bleeding and can be used alone or with desmopressin or VWF-containing products when contraindications are absent. BMJ+1BMJVon Willebrand disease - Symptoms, diagnosis and treatment | BMJ Best Practice USccjmvon Willebrand disease: A guide for the internist | Cleveland Clinic Journal of medicine

For pregnancy, obtain a documented hemostatic plan that addresses delivery, neuraxial anesthesia, postpartum treatment, and factor-level monitoring. The VWD management guideline specifically addresses neuraxial anesthesia during labor and delivery and postpartum management, supporting planned multidisciplinary care rather than relying on historic nonpregnant VWF values. ASHASHASH ISTH NHF WFH 2021 guidelines on the management of von Willebrand disease | Blood Advances | American Society of Hematology

Postpartum bleeding risk warrants explicit discharge instructions and a treatment-access plan because postpartum hemorrhage is a common VWD complication. Select antifibrinolytic therapy cautiously when thromboembolic history or significant hematuria is present. BMJ+1BMJVon Willebrand disease - Symptoms, diagnosis and treatment | BMJ Best Practice USccjmvon Willebrand disease: A guide for the internist | Cleveland Clinic Journal of medicine