DDAVP challenge tests in boys with mild/moderate haemophilia A*

Abstract

Summary. 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 0AE01-0AE3 IU/ml who had a DDAVP challenge test (i.v. 0AE3 lg/kg) following diagnosis. A therapeutic response was defined as a 1 h post-FVIII:C increase at least twofold over baseline and > 0AE3 IU/ml. Of the total group, 29 (47%) boys responded to DDAVP, all of them with mild haemophilia (baseline FVIII:C ‡ 0AE05 IU/ml), yielding a response rate of 57% in this subgroup. Boys who responded to DDAVP had higher baseline FVIII:C levels (mean ± SEM, 0AE17 ± 0AE01 vs 0AE10 ± 0AE01 IU/ml, P < 0AE01) and were older (5AE2 ± 0AE8 vs 3 ± 0AE4 years, P ¼ 0AE02) 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 6AE3 years (median 4AE9, range 0AE5-12AE5), 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.

The use of desmopressin as a hemostatic agent: A concise review

“…While subcutaneous injection (0.3 mg/kg) produces a similar, although slower, response to that seen with intravenous infusion, intranasal inhalation (250 mg) of DDAVP elicits a slower and less marked response, with a maximum FVIII level of *2.5-times the baseline value. Thus, the subcutaneous or intravenous routes of administration should be preferred when a maximum response is required [24,25].…”

Molecular and clinical predictors of inhibitor risk and its prevention and treatment in mild hemophilia A

“…Young children often have markedly lower responses to desmopressin than adults, but they may become responsive at an older age. [27][28][29] The FVIII half-life, typically around 6 to 8 hours, is positively associated with basal and peak VWF antigen levels and patient age. 24 Some mutations are consistently associated with favorable responses (in particular, several of those at risk for inhibitor development; Table 1), whereas promoter, splicing, or intronic mutations respond poorly, and some missense mutations show a reduced FVIII survival 3,24-27 ( Figure 1).…”

“…Although there is a certain consistency of the response within the same mutation, the response to desmopressin is somehow heterogeneous. [24][25][26][27]29 Therefore, the individual response should always be assessed by a test infusion of desmopressin with FVIII measured at least 1 and 4 hours after its administration to ascertain the pattern of response and the rate of clearance.…”

Response to desmopressin in patients with mild hemophilia A caused by the F8 c.1910A>G, p.Asn637Ser mutation

“…If this had been the case, lower increases in FVIII levels after desmopressin infusion would have been seen. In a Canadian study of boys with hemophilia in whom the FVIII response initially failed after desmopressin treatment, a response was seen when they were rechallenged after a mean of 6.3 years [8]. Seary et al [9] found, in their study of 74 boys with 38 different mutations causing moderate or mild hemophilia, that age and FVIII level were strong predictors of response to desmopressin.…”

“…While both the plasma-and platelet-derived molecules can form a functional complex, several studies demonstrate that the two cofactor pools are physically and functionally distinct [2][3][4][5][6][7]. Despite these differences, the entire platelet-derived pool of the procofactor, FV, is endocytosed from the plasma by megakaryocytes [4,8] via a two-receptor system consisting of a specific, unknown FV receptor and low density lipoprotein (LDL) receptor-related protein-1 (LRP-1) [9], an endocytic receptor belonging to a superfamily of proteins related to the LDL receptor [10]. Flow cytometric analyses and fluorescence microscopy indicate that all megakaryocytes express LRP-1 [9,11].…”