Von Willebrand disease, pharmacokinetics, treatment, bleeding, surgery
Conditions
Interventions
A. In patients needing to undergo a DDAVP-test, no intervention will be implemented.
B. In patients requiring treatment with DDAVP and/or VWF-containing concentrate during an elective dental or surgi
Sponsors
Erasmus University Medical Center - Sophia Children's Hospital, University Medical Center Rotterdam
Eligibility
Inclusion criteria
Inclusion criteria: - No minimum or maximum age at inclusion date; - Hemorrhagic symptoms or a family history of von Willebrand disease or low VWF with historically lowest levels of VWF:Ag and/or VWF:Act and/or VWF:Cb <0.60 IU/ml and/or FVIII <0.40 IU/ml (only in type 2N); - Need for DDAVP-testing; and/or - Need for a medical procedure requiring DDAVP and/or VWF replacement therapy during the procedure; or - Bleeding requiring DDAVP and/or VWF replacement therapy; or - Frequent bleeding requiring prophylaxis with VWF-containing concentrate. - Written informed consent in patients 12 years and older, and written parental consent in patients <16 years
Exclusion criteria
Exclusion criteria: - Any other known hemostatic abnormalities; - Acquired VWD; - Presence of VWF antibodies (>0.2 BU) - Withdrawal of (parental) informed consent.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| A. In case of DDAVP-testing: predictive performance of the DDAVP population PK model: reliability of predicted VWF:Act and FVIII levels (IU/ml), defined as difference (%) between predicted and actual VWF:Act and FVIII levels (IU/ml). B. In case of elective procedures and treatment with DDAVP or VWF-containing concentrate: predictive performance of the Bayesian adaptive approach using the population PK model for either DDAVP or VWF-containing concentrate: reliability of predicted VWF:Act and FVIII levels (IU/ml) , defined as difference (%) between predicted and actual VWF:Act and FVIII levels (IU/ml) achieved after dosing according to target levels stated by consensus and treating physician. C. In case of treatment of a bleeding episode with DDAVP or VWF-containing concentrate: predictive performance of the respective population PK models: reliability of predicted VWF:Act and FVIII levels (IU/ml), defined as difference (%) between predicted and actual VWF:Act and FVIII levels (IU/ml) achieved after dosing. D. In patients receiving prophylaxis with a VWF-containing concentrate: predictive performance of the respective population PK models: reliability of predicted VWF:Act and FVIII levels (IU/ml), defined as difference (%) between predicted and actual VWF:Act and FVIII levels (IU/ml) achieved after dosing. | — |
Secondary
| Measure | Time frame |
|---|---|
| Only applicable in B, C and D: 1. Number and timing of DDAVP infusions and/or timing and dosing (IU/kg) of VWF-containing concentrate infusions. 2. Hemostasis as quantified by hemoglobin values pre- and postoperatively, amount of blood loss (ml), incidence of bleeding and thrombosis, and need for blood transfusion and/or (re)-operation. 3. Duration of hospitalization (days), number of outpatient clinic visits. 4. Feasibility of intervention with regard to patient and physician satisfaction and economic impact. Only applicable in case of DDAVP-testing or treatment with DDAVP. 5. DDAVP plasma concentrations (pg/ml). | — |
Contacts
Public ContactWala Al Arashi
Erasmus MC - Sophia Children's Hospital, University Medical Center Rotterdam
Outcome results
None listed