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DDAVP response in moderate hemophilia A
lifetime lowest FVIII:C is inversely associated. This is most likely due to the reciprocal effect of higher pre-DDAVP FVIII:C on the relative increase, since it is the denominator of our outcome variable. There may be an effect of stress- induced increase of FVIII, depicted in Table 2B by a differ- ence between lowest lifetime and pre-DDAVP FVIII:C. However, we did not adjust for age and mutation, as the effect of age on FVIII:C is dependent on mutation.33
The variation in the incremental response was explained
for only 29% by the four identified predictors. This is less than the explained variation in peak response (65%). We believe that further analyses of different mutation groups might help to reveal the observed discrepancy in explained variance.
Mutation analysis
Two studies presented the DDAVP response for different mutations in non-severe patients.15,16 All moderate patients
Figure 2. Mutations and associated response to 1-Deamino-8-D- ArgininVasoPressin (desmopressin; DDAVP). All mutations were present in three patients, except for the Pro149Arg and Arg2169His mutation (n=6 and n=21, respectively). The size of the diagrams reflects the number of patients.
Table 4A. Multiple linear regression model of predictors of peak factor VIII (FVIII:C) explaining 65% of peak FVIII:C.
Table 4B. Multiple linear regression model of incremental response (peak factor VIII [FVIII:C]/pre-1-Deamino-8-D-ArgininVasoPressin [desmopressin; DDAVP] FVIII:C) explaining 29% of incremental response.
95% Confidence Interval
Unstandardized 95%Confidence
β
Interval
5.88 2.7 0.18 -0.09 -0.01 -0.46
Coefficients
3.7 1.52 2.51 2.33 0.17 0.15 -0.12 -0.14 -0.03 -0.04 -2.74 -5.02
Unstandardized
Intravenous administration Pre-DDAVP FVIII:C (IU/dL) DVWF:Ag (IU/dL)
Pre- DDAVP VWF:Ag (IU/dL) Peak VWF:Act (IU/dL)
Age (log, in yrs)*
β
Coefficients
DVWF:Ag (IU/dL) 0.05 0.04 Pre-DDAVP VWF:Ag (IU/dL) -0.03 -0.04 Lifetime lowest FVIII:C (IU/dL) -1.47 -1.87 Interaction term -0.19 -0.25 (age*pre-DDAVP FVIII:C)
0.05 -0.15 -1.07 -0.13
*All predictors had a P-value <0.001, except for that of age (P=0.019). Peak FVIII:C increases 2.5 IU/dL for every unit increase in pre-1-Deamino-8-D-ArgininVasoPressin (desmopressin; DDAVP) FVIII:C and 0.165 IU/dL for every unit increase in D von Willebrand factor antigen (VWF:Ag). In comparison to subcutaneous or intranasal administration, the response after intravenous administration appears to be 3.7-fold higher, although this is not statistically significant due to low patient numbers. For every unit increase in baseline VWF:Ag, peak von Willebrand factor activity (VWF:Act) and age, peak FVIII:C decreases by 0.12 IU/dL, 0.03 IU/dL and 2.74 log years, respectively.
*All predictors had a P-value <0.001. For every unit increase in D von Willebrand fac- tor antigen (VWF:Ag),the incremental response increases by 0.047 IU/dL,whereas for every unit increase of pre-DDAVP VWF:Ag, lifetime lowest FVIII:C, and the interaction term, incremental response decreases by 0.026 IU/dL, 1.469 IU/dL, and 0.187 year*IU/dL, respectively.
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