von Willebrand disease: A guide for the internist

Varinder Kaur; Omar Elghawy; Saarang Deshpande; David Riley

doi:10.3949/ccjm.91a.22033

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TABLE 1

International Society of Thrombosis and Haemostasis classification of von Willebrand disease

Type Subtype	VWD type 1		VWD type 2				VWD type 3
Type Subtype	Classic	1C	2A	2B	2M	2N	VWD type 3
Frequency	Common (70% of cases)		Uncommon (25% of cases)				Rare (5% of cases)
Pathophysiology	Mutations result in partial quantitative deficiency of functionally normal VWF		Qualitative defects in VWF				Almost complete quantitative deficiency of VWF
Specific mechanism	Decreased synthesis of VWF due to various genetic mutations	Increased clearance of available VWF in circulation	Mutations result in fewer glycoprotein Ib binding sites and less effective platelet clot formation	Mutations increase affinity of glycoprotein Ib binding site and clearance of high-molecular-weight multimers	Mutations decrease affinity of glycoprotein Ib site or decrease VWF-collagen interaction	Mutation in factor VIII binding site decreases affinity of VWF for factor VIII	Almost complete quantitative deficiency of VWF
Inheritance	Autosomal dominant	Autosomal dominant	Autosomal dominant	Autosomal dominant	Autosomal dominant	Autosomal recessive	Autosomal recessive
Clinical phenotype	Mild to moderate mucocutaneous bleeding	Mild to moderate mucocutaneous bleeding	Moderate to severe mucocutaneous bleeding	Moderate to severe mucocutaneous bleeding	Severe mucocutaneous bleeding	Hemophilialike bleeding	Severe mucocutaneous and hemophilia-like bleeding
Response to desmopressin	Very effective in treating minor bleeding episodes	Used to diagnose type 1C (> 30% decrease in VWF 4 hours after infusion) Ineffective in treatment of type 1C VWD	May respond to desmopressin Recommend challenge before therapeutic administration	Desmopressin usually contraindicated due to thrombocytopenia	May respond to desmopressin Recommend challenge before therapeutic administration	May respond to depression Recommend challenge before therapeutic administration	Recommend avoiding desmopressin

VWD = von Willebrand disease; VWF = von Willebrand factor
Data adapted from reference 13.

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TABLE 2

Diagnostic laboratory criteria for each type of von Willebrand disease

Type Subtype	VWD type 1		VWD type 2				VWD type 3
Type Subtype	Classic	1C	2A	2B	2M	2N	VWD type 3
Ratio of VWF activity to VWF antigen	Normal (about 1)		< 0.6				Markedly low or undetectable VWF activity and antigen levels
Factor VIII levels	Normal or mildly low	Normal or mildly low	Normal or mildly low	Normal or mildly low	Normal or mildly low	Moderately low relative to VWF antigen	Very low
VWF multimer analysis	Full spectrum of multimers, but all at low level	Full spectrum of multimers, but all at low level	Absence of high- and intermediate-molecular-weight multimers	Absence of high-molecular-weight multimers	Normal multimer pattern	Normal multimer pattern	Minimal or complete absence of VWF multimers
Specific testing to diagnose subtype	None	Elevated ratio of VWF propeptide to VWF antigen > 30% decrease in VWF 4 hours after infusion of desmopressin	Genetic testing	Increased ristocetin-induced platelet aggregation Sensitivity to low-dose ristocetin Genetic testing	Decreased ristocetin-induced platelet aggregation Low VWF-collagen binding capacity Genetic testing	Decreased binding of VWF to factor VIII Prolonged partial thromboplastin time Genetic testing	None