VWF Activity to Antigen Ratio Calculator
VWF Activity to Antigen Ratio Calculator
Divide von Willebrand factor activity by von Willebrand factor antigen. A ratio below 0.7 says the factor present is not working properly — a qualitative type 2 defect rather than simply having too little of it, which changes the treatment.
VWF activity : antigen ratio
Activity ÷ antigenVWF:RCo 38 IU/dL, VWF:Ag 70 IU/dL
Formula
Below 0.7 on a platelet-dependent activity assay suggests type 2 von Willebrand disease
- VWF activity
- a functional measurement — ristocetin cofactor (VWF:RCo), or the recombinant glycoprotein Ib assays VWF:GPIbM and VWF:GPIbR, which are more precise and are preferred where available
- VWF:Ag
- an immunological measurement of how much von Willebrand factor protein is present, functional or not
- 0.7, not 0.5
- the ASH ISTH NHF WFH 2021 guideline suggests against the older 0.5 cut-off and recommends 0.7, which raises sensitivity for type 2 disease from around 58–79% to about 90%
- the units cancel
- both results are reported in IU/dL or as a percentage of normal, so the ratio is dimensionless. Make sure both are in the same unit before dividing
- what the ratio does not tell you
- whether the levels are low at all. A ratio of 1.0 with both values at 20 IU/dL is severe type 1 disease; a ratio of 1.0 with both at 100 is normal. Read the ratio and the absolute levels together
Worked example
VWF:RCo 38 IU/dL, VWF:Ag 70 IU/dL
38 ÷ 70 = 0.54
Below the 0.7 cut-off, so the factor present is not functioning normally
Note that the antigen at 70 IU/dL is within the normal range — the quantity is fine and the quality is not
A ratio calculation that looked only at the antigen would have called this patient normal
Next: repeat on a fresh sample, then multimer analysis and ristocetin-induced platelet aggregation to separate type 2A, 2B and 2M
Reading the ratio alongside the levels
| VWF:Ag | Activity : antigen ratio | Interpretation |
|---|---|---|
| Below 30 IU/dL | 0.7 or above | Type 1 von Willebrand disease — a quantitative deficiency, diagnosed at this level regardless of bleeding symptoms |
| 30 to 50 IU/dL | 0.7 or above | Type 1 disease where abnormal bleeding is documented; otherwise low von Willebrand factor, which is a risk factor rather than a diagnosis |
| Any level | Below 0.7 | A qualitative defect — type 2 disease. Subtype with multimers and ristocetin-induced platelet aggregation before choosing treatment |
| Below 3 IU/dL, activity undetectable | Not calculable | Type 3 disease — essentially no von Willebrand factor. Factor VIII is also markedly low, and bleeding resembles moderate haemophilia |
| Normal | 0.7 or above | No von Willebrand defect on this testing. If the bleeding history is convincing, repeat: a single normal set of results does not exclude the diagnosis |
Why a normal result does not settle it
| Influence | Effect on VWF | Practical consequence |
|---|---|---|
| Blood group O | Levels roughly 20–30% lower than groups A, B and AB | The commonest reason for a borderline result. The 2021 guideline nevertheless says ABO-specific reference ranges are not required for diagnosis, so do not explain away a low level on blood group alone |
| Acute-phase response — infection, inflammation, surgery, trauma | Rises, sometimes into the normal range | A sample taken during or shortly after an acute illness can be falsely reassuring. Repeat when well |
| Pregnancy | Rises progressively, often two- to threefold by the third trimester | Testing in pregnancy can miss type 1 disease entirely. Levels fall again within days of delivery, which is when postpartum haemorrhage occurs |
| Oestrogen-containing contraception and hormone replacement | Raises levels | Note what the patient is taking when the sample is interpreted |
| Stress, exercise, a difficult venepuncture, adrenaline | Raises levels acutely | A screaming child or a struggled draw can normalise a result on the spot |
| Age | Rises steadily through adult life | A diagnosis made in youth may not be reproducible on levels alone in later life, though the bleeding phenotype persists |
How much there is, and whether it works
Von Willebrand disease is diagnosed by asking two separate questions, and the ratio on this page answers the second. The antigen assay measures how much von Willebrand factor protein is present. The activity assay — ristocetin cofactor traditionally, or one of the newer recombinant glycoprotein Ib assays — measures how well that protein does its job of binding platelet glycoprotein Ib. Dividing one by the other separates a patient who simply has too little normal factor, which is type 1 disease, from one who has a reasonable quantity of a factor that does not work, which is type 2. That distinction changes management: desmopressin releases stored von Willebrand factor and works well in most type 1 disease, but it is unhelpful in type 2M, of limited value in type 2A, and can worsen the thrombocytopenia of type 2B.
The threshold moved recently and it is worth knowing which one your laboratory is using. The 2021 ASH, ISTH, NHF and WFH joint guideline suggests against the long-standing cut-off of 0.5 and recommends 0.7 instead, on the evidence that 0.5 has a sensitivity for type 2 disease of only about 58 to 79% against roughly 90% at 0.7. The higher threshold means more patients are investigated further, which the panel accepted as the better error: missing a qualitative defect means treating a patient with a drug that will not work for them, sometimes on the morning of surgery.
The ratio is only as good as the activity assay underneath it. Ristocetin cofactor is imprecise, with a coefficient of variation often around 20 to 30% and a lower limit of quantitation that makes ratios unreliable when activity is genuinely low. It is also falsely reduced by the D1472H sequence variant, which is commoner in Black populations and causes no bleeding tendency at all — a well documented route to over-diagnosis. The recombinant glycoprotein Ib assays, VWF:GPIbM and VWF:GPIbR, avoid that interference and are more reproducible, and the guideline prefers them where they are available. A collagen-binding ratio is a different tool again, used to detect loss of high-molecular-weight multimers in types 2A and 2B, and the 0.7 cut-off does not transfer to it.
Finally, the result has to be read in the knowledge that von Willebrand factor is an acute-phase reactant. It rises with infection, inflammation, surgery, trauma, exercise, adrenaline, oestrogen and pregnancy — by two- to threefold at term, which is why testing in pregnancy misses type 1 disease and why the postpartum haemorrhage arrives after the levels have fallen again. In the other direction, blood group O carries physiologically lower levels, roughly 20 to 30% below groups A, B and AB, and is by far the commonest reason a result sits just below a reference limit. The 2021 guideline is deliberately careful here: it says ABO-specific reference ranges are not required for diagnosis, which means a low level in a group O patient with a bleeding history is not to be dismissed as constitutional. A single normal set of results does not exclude the diagnosis, and a convincing bleeding history — measured with a validated bleeding assessment tool rather than an impression — is reason to repeat.
Frequently asked questions
What VWF activity to antigen ratio suggests type 2 von Willebrand disease?
Below 0.7 on a platelet-dependent activity assay. The 2021 ASH ISTH NHF WFH guideline recommends this cut-off in preference to the older 0.5, because 0.5 has a sensitivity for type 2 disease of only around 58 to 79% against about 90% at 0.7. Confirm on a repeat sample before committing to the subtype workup.
Which activity assay should be used?
A recombinant glycoprotein Ib assay, VWF:GPIbM or VWF:GPIbR, where it is available. Ristocetin cofactor has a coefficient of variation of roughly 20 to 30%, performs poorly at low activity, and is falsely reduced by the D1472H variant, which is commoner in Black populations and causes no bleeding disorder. Collagen binding answers a different question.
Does blood group O cause low von Willebrand factor?
Yes. Group O individuals have levels roughly 20 to 30% lower than groups A, B and AB, which is the commonest reason for a borderline result. The 2021 guideline nonetheless says ABO-specific reference ranges are not required for diagnosis, so a low level with a bleeding history should be investigated rather than attributed to blood group.
Can normal results exclude von Willebrand disease?
Not from a single sample. Von Willebrand factor is an acute-phase reactant and rises with infection, inflammation, surgery, stress, exercise, oestrogen and pregnancy. Testing during or shortly after any of these can give a falsely normal result. Where the bleeding history is convincing, repeat when the patient is well and off oestrogen.
What does the ratio not tell you?
Whether the levels are low at all. A ratio of 1.0 is normal whether both values sit at 100 IU/dL or at 20 IU/dL, and the second patient has severe type 1 disease. Read the ratio alongside the absolute antigen and activity levels and the bleeding history, never on its own.
Related calculators
References
- James PD, Connell NT, Ameer B, et al. ASH ISTH NHF WFH 2021 guidelines on the diagnosis of von Willebrand disease. Blood Adv. 2021;5(1):280–300.
- Flood VH, Gill JC, Morateck PA, et al. Common VWF exon 28 polymorphisms in African Americans affecting the VWF activity assay by ristocetin cofactor. Blood. 2010;116(2):280–286.
- Gill JC, Endres-Brooks J, Bauer PJ, Marks WJ, Montgomery RR. The effect of ABO blood group on the diagnosis of von Willebrand disease. Blood. 1987;69(6):1691–1695.
Medical Disclaimer: The tools and content provided here are for educational and reference purposes only. They are not intended to substitute for professional medical advice, diagnosis, or treatment. Clinical decisions should always be based on the comprehensive assessment of a qualified healthcare professional.