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DDAVP challenge tests in boys with mild/moderate haemophilia A
Shoshana Revel-Vilk1, Victor S Blanchette, Cathy Sparling
1Department of Paediatrics, The Hospital for Sick Children and the University of Toronto, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada.
Abstract:
Desmopressin (DDAVP) increases plasma factor VIII coagulant activity (FVIII:C) levels in patients with mild/moderate haemophilia A. In some subjects, FVIII can be increased to haemostatic levels, thereby avoiding use of factor VIII concentrates. We reviewed our hospital's experience with 62 boys with FVIII:C levels 0.01-0.3 IU/ml who had a DDAVP challenge test (i.v. 0.3 microg/kg) following diagnosis. A therapeutic response was defined as a 1 h post-FVIII:C increase at least twofold over baseline and > 0.3 IU/ml. Of the total group, 29 (47%) boys responded to DDAVP, all of them with mild haemophilia (baseline FVIII:C > or = 0.05 IU/ml), yielding a response rate of 57% in this subgroup. Boys who responded to DDAVP had higher baseline FVIII:C levels (mean +/- SEM, 0.17 +/- 0.01 vs 0.10 +/- 0.01 IU/ml, P < 0.01) and were older (5.2 +/- 0.8 vs 3 +/- 0.4 years, P = 0.02) than those who failed to do so. The association between DDAVP response and age, however, remains unclear: seven boys who failed the initial challenge test responded to re-challenge after a mean of 6.3 years (median 4.9, range 0.5-12.5), increasing the response rate in boys with mild haemophilia to 71%. Age and FVIII:C association with DDAVP response are both important in boys with mild/moderate haemophilia A. Absence of response to DDAVP should therefore be confirmed by later re-challenge.
Insights
Desmopressin (DDAVP) can increase factor VIII levels in boys with mild/moderate hemophilia A, potentially avoiding factor concentrates. Response is linked to higher baseline factor VIII and older age, with re-challenge confirming efficacy.
Area of Science:
- Hematology
- Pediatric Medicine
- Pharmacology
Background:
- Hemophilia A is a bleeding disorder characterized by low levels of factor VIII (FVIII).
- Desmopressin (DDAVP) is a synthetic analog of vasopressin used to increase FVIII levels.
- Mild/moderate hemophilia A patients may benefit from DDAVP to achieve hemostatic FVIII levels, avoiding factor concentrates.
Purpose of the Study:
- To evaluate the efficacy of desmopressin (DDAVP) in increasing plasma factor VIII coagulant activity (FVIII:C) in boys with mild/moderate hemophilia A.
- To identify factors influencing DDAVP response in this patient population.
- To determine the optimal strategy for assessing DDAVP efficacy, including the role of re-challenge.
Main Methods:
- A retrospective review of 62 boys with mild/moderate hemophilia A who underwent a DDAVP challenge test (intravenous 0.3 microg/kg).
- Therapeutic response defined as a twofold increase in FVIII:C to > 0.3 IU/ml within 1 hour post-administration.
- Analysis of baseline FVIII:C levels, age, and response to initial and subsequent DDAVP challenges.
Main Results:
- 29 out of 62 boys (47%) showed a therapeutic response to DDAVP.
- All responders had mild hemophilia (baseline FVIII:C >= 0.05 IU/ml), with a subgroup response rate of 57%.
- Responders had significantly higher baseline FVIII:C (0.17 vs 0.10 IU/ml) and were older (5.2 vs 3 years) than non-responders.
- Seven boys who initially failed DDAVP responded upon re-challenge, increasing the mild hemophilia response rate to 71%.
Conclusions:
- DDAVP is effective in a significant proportion of boys with mild/moderate hemophilia A, particularly those with higher baseline FVIII:C and older age.
- Age and baseline FVIII:C are important predictors of DDAVP response.
- Absence of response to an initial DDAVP challenge should be confirmed by a later re-challenge to maximize the identification of potential responders.