Differential diagnosis of von Willebrand disease (VWD)

Condition	Cause	Laboratory testing
Platelet function disorders such as GT, BSS, and granule disorders	Pathogenic variants affecting platelet function genes	Platelet count showing thrombocytopenia in some cases and normal platelet count in others Blood smear review showing abnormal platelet morphology in some cases Platelet aggregometry showing a pattern specific to the syndrome
Platelet-type VWD^*	Pathogenic variants affecting the VWF receptor on platelets	Platelet count showing thrombocytopenia VWF activity reduced Low ratio of VWF activity to VWF antigen Loss of high molecular weight VWF multimers Increased aggregation with low concentrations of ristocetin
Mild hemophilia	Pathogenic variants affecting clotting factor genes (F8, F9, or F11)	aPTT may be prolonged in some cases and normal in others Factor activity level showing decrease in the relevant factor
Acquired factor inhibitors	Autoantibodies against clotting factor proteins	aPTT or PT may be prolonged (more commonly aPTT prolongation due to factor VIII inhibitors) Factor activity level showing decrease in the relevant factor Inhibitor testing showing failure of the aPTT or PT to correct with control plasma
Acquired von Willebrand syndrome (AVWS)	VWF destruction or impaired production due to various causes	VWF antigen and activity showing reductions
Bleeding disorder of unknown cause (BDUC)	Unknown after excluding other rare causes	Testing to exclude VWD and conditions listed above Testing for less common disorders such as: Connective tissue disorders Vascular disorders such as HHT Scurvy Rare disorders of clotting or fibrinolysis
Immune thrombocytopenia (ITP)	Autoantibodies against platelet antigens	Platelet count showing thrombocytopenia (NOTE: thrombocytopenia may be seen in type 2B VWD but is not typical of other VWD subtypes) Blood smear review showing decreased platelet number with normal morphology (may be larger than average but not giant)

Bleeding phenotypes may also differ among these disorders. Refer to UpToDate for clinical presentation and evaluation, including details and sequence of testing.

aPTT: activated partial thromboplastin time; BSS: Bernard-Soulier syndrome; GT: Glanzmann thrombasthenia; HHT: hereditary hemorrhagic telangiectasia; PT: prothrombin time; VWF: von Willebrand factor.

* Platelet-type VWD (also called pseudo-VWD) is a rare inherited platelet function disorder in which gain-of-function variants in gene encoding a component of the VWF receptor (glycoprotein [GP] Ib/IX/V) cause increased binding of VWF to platelets and rapid clearance of the GPIb/IX/V-VWF complex, leading to thrombocytopenia and low VWF activity in VWF functional assays.

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Differential diagnosis of von Willebrand disease (VWD)