von Willebrand Disease| CSL Behring Medical Affairs

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von Willebrand Disease

Disease Background

Von Willebrand Disease (VWD) is an autosomal inherited bleeding disorder caused by a deficiency or dysfunction of von Willebrand factor (VWF) and is the most common bleeding disorder, found in up to 1% of the US population.

VWF, along with factor VIII (FVIII), is a key molecule in platelet aggregation and adhesion and is critical to prevent bleeding via blood clotting.

Typical symptoms of VWD include easy bruising, epistaxis, gingival bleeding, surgical bleeding, and heavy menstrual bleeding.

Characteristics of Types of VWD

Type	Classification	Description	Bleeding	Incidence³
1	Quantitative	Partial deficiency of VWF	Variable from mild to moderate	~85%
2A	Qualitative	Defects in multimerization	Variable from moderate to severe	10-15%
2B	Qualitative	Increase in spontaneous platelet binding	Variable from moderate to severe	10-15%
2M	Qualitative	Defects in ligand binding with intact multimers	Variable from moderate to severe	10-15%
2N	Qualitative	Defects in FVIII binding	Variable from moderate to severe	10-15%
3	Quantitative	Severe deficiency of VWF	Severe	<1%

VWF, von Willebrand factor

Diagnostic Process

The National Institute of Health recommends that assessments for diagnosis of VWD occur in two main stages:

1. Evaluation of clinical history

Family history and personal bleeding history (spontaneity and severity, sites of bleeding, duration of bleeding, type of injury associated with bleeding, ease with which bleeding can be stopped)

2. Laboratory evaluations

chart of diagnositic process to determine von Willebrand Disease

^aplatelet-dependent VWF activity

Treatment Options1,3,4,5

VWD Type	Recommended Treatment
1	Desmopressin (if unresponsive to desmopressin use VWF/FVIII concentrates)
2	VWF/FVIII concentrates
3	VWF/FVIII concentrates

VWF concentrate dosing recommendation¹

Major surgery/bleeding:

Loading dose	Maintenance dose	Therapeutic goal
40-60 U/kg	20-40 U/kg every 8 to 24 hours	Trough VWF:RCo and FVIII>50 IU/dL for 7-14 days

Minor surgery/bleeding:

Loading dose	Maintenance dose	Therapeutic goal
30-60 U/kg	20-40 U/kg every 12 to 48 hours	Trough VWF:RCo and FVIII>50 IU/dL for 3-5 days

* Antifibinolytic agents in combination with topical agents, or with desmopressin and VWF/FVIII concentrates, can also be used¹

Treatment Guidelines

ASH ISTH NHF WFH 2021 Guidelines on the Diagnosis and Management of von Willebrand Disease

NHLBI 2008 Guidelines

1.Nichols WL, Hultin MB, James AH, et al. Von Willebrand Disease. Haemophilia 2008;14(2):171–232.2.Data and statistics on von Willebrand disease. Available from: https://www.cdc.gov/ncbddd/vwd/data.html 3.Sharma R, Flood VH. Advances in the diagnosis and treatment of Von Willebrand Disease. Hematology Am Soc Hematol Educ Program. 2017(1):379–384. 4.Ng C, Motto DG, Di Paola J. Diagnostic Approach to VWD. Blood 2015; 125(13):2029–2037. 5. Federici A. Management of inherited Von Willebrand Disease in 2006.. Semin Thrombosis Hemostasis. 2006; 32:616–620.