About This Calculator

The Von Willebrand Factor Dose Calculator is a clinical support tool designed to assist healthcare professionals in determining the appropriate dosage of VWF-containing concentrate for patients with Von Willebrand Disease (VWD). It bases its calculations on patient weight, clinical indication, baseline and target VWF activity levels, and the specific product being used. This guide provides an overview of the calculator’s functions, inputs, and outputs to ensure proper use.

Calculator Outputs Explained

Upon entering the required parameters, the calculator provides a detailed summary to guide administration:

• Calculated VWF Dose: The total required dose of Von Willebrand Factor Ristocetin Cofactor (VWF:RCo) in International Units (IU), calculated using the standard pharmacokinetic formula.
• Co-administered FVIII Dose: The amount of Factor VIII (FVIII) that will be delivered along with the VWF dose, based on the specific product’s VWF:FVIII ratio. This is critical for products that contain both factors.
• Vials to Administer: A practical recommendation for the combination of available vial sizes to achieve the target dose, aiming to minimize waste.
• Total Administered Dose: The final VWF:RCo and FVIII dose that will be administered based on the selected vial combination. This may be slightly higher than the calculated dose.
• Maintenance Recommendations: For major bleeding or surgery, the tool provides guidance on subsequent dosing to maintain therapeutic levels.

How to Use the Calculator

Follow these steps to obtain a dosing recommendation:

1. Enter Patient Weight: Input the patient’s weight and select the correct unit (kg or lbs). The calculator will convert lbs to kg for the formula.
2. Select Clinical Indication: Choose the reason for treatment from the dropdown menu (e.g., Minor Bleeding, Major Surgery). This automatically populates a recommended target VWF activity level.
3. Input Baseline VWF: Enter the patient’s most recent VWF:RCo activity level (in IU/dL or %). If unknown, you may leave it blank or enter 0.
4. Adjust Target VWF (Optional): The target VWF activity is pre-filled based on the indication but can be manually adjusted based on clinical judgment.
5. Select VWF Product: Choose the specific VWF-containing concentrate you plan to use (e.g., Humate-P, Vonvendi). This is crucial as different products have different VWF:FVIII ratios.
6. Confirm Vial Sizes: After selecting a product, check the boxes corresponding to the vial sizes you have available in your pharmacy.

Dosing Overview

The calculator employs a standard formula for VWF dosing:

Dose (IU) = Weight (kg) × (Target VWF% – Baseline VWF%) × 0.5

This formula is based on an assumed volume of distribution for VWF, where approximately 2 IU/kg of VWF:RCo is needed to raise the plasma level by 1 IU/dL (or 1%). For major bleeding events or surgery, an initial loading dose is calculated to achieve a peak level, followed by maintenance doses to maintain a therapeutic trough level (e.g., >50 IU/dL).

Switching Between Products

When switching between VWF concentrate products, clinicians must consider the different ratios of VWF:RCo to FVIII. For example, Humate-P has a higher VWF:FVIII ratio than Wilate. Switching can impact the amount of FVIII co-administered, which may be clinically significant. Recombinant VWF (Vonvendi) contains no FVIII and may require separate FVIII administration. Always consult a hematologist and product-specific guidelines when switching therapies.

Missed Dose

If a patient on a routine prophylaxis schedule misses a dose, they should contact their healthcare provider or hemophilia treatment center for instructions. The action required will depend on the time since the missed dose and the patient’s bleeding risk. Do not double the next dose to make up for a missed one unless specifically instructed to do so.

Safety Alerts

The calculator may display important clinical notes based on the calculation:

Frequently Asked Questions (FAQ)

Why is the target VWF activity pre-filled?

The calculator pre-fills a standard target VWF level based on established clinical guidelines for the selected indication (e.g., 50% for minor bleeding, 90-100% for major surgery). However, this is a suggestion and can be manually overridden based on institutional protocols or specific patient needs.

How does the calculator determine the best vial combination?

The tool uses a practical algorithm that prioritizes using the largest available vials first to meet the calculated dose, then adds smaller vials as needed to get as close as possible to the target dose without significant under-dosing. This approach aims to simplify administration and minimize waste.

What should I do if my patient’s baseline VWF is unknown?

If the baseline VWF:RCo level is unknown or not recently measured, you can enter ‘0’ or leave the field blank. The calculation will then be based on raising the level from a presumed baseline of zero to the target, which is a common and safe approach in emergency settings.

What does the VWF:FVIII ratio mean for different products?

This ratio indicates the relative amounts of VWF activity to FVIII activity in the concentrate. A product like Humate-P has a ratio of ~2.4:1 (more VWF than FVIII), while Wilate has a 1:1 ratio. This is critical for managing both VWF and FVIII levels appropriately.

Can I use this calculator for pediatric patients?

Yes, the dosing formula is weight-based and applicable to both adult and pediatric patients. However, pharmacokinetic parameters can vary, especially in very young children. All calculations for pediatric patients should be carefully reviewed by a specialist.

Why does Vonvendi need special consideration for FVIII?

Vonvendi is a recombinant VWF product and does not contain any Factor VIII. In VWD patients, low VWF often leads to secondarily low FVIII levels. While administering Vonvendi will eventually stabilize the patient’s own FVIII, co-administration of a separate recombinant FVIII product may be needed for initial hemostasis.

Is the dosing constant of 0.5 always accurate?

The value of 0.5 (or a recovery of 2 IU/dL per 1 IU/kg) is a widely accepted average. However, individual patient recovery can vary. Dosing should always be guided by clinical response and, when possible, laboratory monitoring of VWF levels.

What happens if I enter the patient’s weight in pounds (lbs)?

The calculator will automatically convert the weight from pounds to kilograms using the standard conversion factor (1 kg ≈ 2.20462 lbs) before applying the dosing formula, ensuring the calculation is accurate regardless of the unit selected.

References

• CSL Behring. (2023). Humate-P Prescribing Information. U.S. Food and Drug Administration. View FDA Label
• Octapharma. (2023). Wilate Prescribing Information. U.S. Food and Drug Administration. View FDA Label
• Grifols. (2023). Alphanate Prescribing Information. U.S. Food and Drug Administration. View FDA Label
• Takeda Pharmaceuticals. (2022). Vonvendi Prescribing Information. U.S. Food and Drug Administration. View FDA Label
• Nichols, W. L., Hultin, M. B., James, A. H., et al. (2008). von Willebrand disease (VWD): evidence-based diagnosis and management guidelines, the National Heart, Lung, and Blood Institute (NHLBI) Expert Panel report (USA). Haemophilia, 14(2), 171–232. View on PubMed