Clinical Efficacy and Safety Versus Biological Response of Desmopressin (DDAVP) In Inherited Von Willebrand Disease (VWD) Types 1 and 2: Initial Results From the International Study Group on DDAVP In VWD In a Cohort of 229 Patients
Bibliographic record
Abstract
Abstract Abstract 238 Background: Desmopressin (DDAVP) is the treatment of choice for most patients with mild-moderate forms of von Willebrand Disease (VWD) because it can induce the release of von Willebrand Factor (VWF) from cellular compartments. However, despite the widespread use of DDAVP since 1977, there are only a few prospective clinical trials aimed at determining benefits and limits of this approach. Aims and design of the study: To correlate efficacy and safety with biological response of DDAVP in a large cohort of VWD1 and VWD2 patients followed-up for 24 months in a prospective observational study organized on behalf of the Working Party on DDAVP in VWD of the ISTH-SSC on VWF and of Italian Association of Hemophilia Centers (AICE). The study is registered at the EMEA with number EudraCT-2005-004496-38. Patients and Methods: VWD patients were enrolled after obtaining Ethical approval from local IRB. Inclusion criteria: inherited VWD without any age restriction, with previous diagnosis of VWD1 and VWD2 according to ISTH recommendations. Biological response: At enrollment patients were exposed to 0.3 ug/kg DDAVP intravenous injection and to blood withdrawal for measuring VWF/FVIII activities before and after 0.5, 1, 2 and 4 hours. Complete: both VWF:RCo and FVIII:C >50 IU/dL at 2 hours; partial: VWF:RCo or FVIII:C <50 IU/dL but increased at least 3-fold; absent: neither criterion. Clinical Response. Excellent: no excessive bleeding; Good: excess bleeding without need for VWF concentrate; Poor: excess bleeding with need for VWF concentrate. Statistical analyses were performed only on confirmed patients after the blind and independent evaluation by 2 members of the Steering Committee on these criteria: VWD=baseline levels of VWF:RCo <55 U/dL; VWD2= baseline VWF:RCo/Ag ratio≤ 0.6; VWD1 accelerated clearance: rapid increase of VWF:RCo/FVIII after 0.5–1 hrs with return to baseline levels after 2–4 hrs. Results: 229/268 (85%) patients enrolled at 13 participating Centers in Argentina, Brazil, Canada, Germany, Italy and Hungary were found to meet the inclusion criteria. Demographic data and lab tests (mean+SD) at baseline were as follows: Among VWD2, VWD2A(n=15), VWD2B(n=1), VWD2M(n=12), VWD2N(n=3) were identified. Biological response was complete, partial and absent in 89%, 10% and 1% of VWD and correlated with baseline levels of VWF:RCo<30 U/dL (Fisher's exact =0.001). Among VWD1, those (n=15) with C1130F and R1205H mutations showed accelerated clearance. During the 24-month follow-up, 62/86 (72%) patients received >1 injection of DDAVP for bleedings (n=102), deliveries (n=13), dental extractions (n=27), minor/major surgeries (n=46). Total number of injections was 652 with median, range/episode during bleedings (2,1-12), deliveries (3,1-3), dental extractions (1,1-6), surgeries (3.6,1-11). Clinical efficacy was excellent/good in bleedings (92%), deliveries (85%), dental extractions (100%), surgeries (91%). Poor efficacy was observed in 6 cases with VWD2A (n=4) during GI bleedings (n=3) or abdominal surgery (n=1) and VWD1 (n=2) during deliveries and surgery. Side effects observed in 16 patients were mainly minor, such as headache, facial flushing and tachycardia; water retention was reported in 2 cases (1 delivery, 1 surgery) only after >6 injections of the drug. Conclusions: Based on the results of this prospective clinical trial, we confirm that DDAVP is an effective and safe drug at low costs for managing patients with VWD1 and VWD2 once tested for their biological response: therefore it should be always considered as the first approach during bleedings and major/minor surgeries in responsive VWD patients. Disclosures: Federici: CSL Behring: Honoraria, Research Funding.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".