Factor VIII response to vasopressin in nephrogenic diabetes insipidus

gested that the factor VIII response to DDAVP is a useful test for diagnosing NDI and for identifying carriers. Subsequently, Ohzeki et al., 2 however, showed strong FVIIIC and FVIIIR:Ag responses after DDAVP stimulus of a neonate with NDI. We studied the increase in the levels of FVIIIR:Ag and FVIIIC after DDAVP stimulation in two NDI patients, respectively aged 2 and 5 years, and their obligate carrier mothers. DDAVP (0.30 #g/kg; maximum dose, 24 ~g) was diluted to a final concentration of 0.5 ~g/ml in physiologic saline solution and infused intravenously for 20 minutes. Venous blood samples were collected just before and 1 hour after infusion. FVIIIR:Ag was assayed by quantitative immunoeleetrophoresis with commercial monospecific antiserum (Clottimmune, aggregated human 3,-globulin-associated protein, Behringwerke, Marburg, Germany). FVIIIC was assayed in fresh samples by a one-stage method based on the partial thromboplastin time, with factor VIII-deficient plasma (Instrumentation Laboratories, Lexington, Ky.) used as substrate. Factor VIII responses were compared with mean _ 2 SD for the control group (z score). As shown in the Table, after DDAVP stimulation the first patient had no marked increase in either FVIIIC or FVIIIR:Ag levels; the second patient had a normal increase in the FVIIIC level but no FVII1R:Ag response. In the two obligate carriers, as in the second patient, there was a normal increase of FVIIIC after stimulus but no increase of FVIIIR:Ag. Our results partially differ from those of Kobrinsky. A high response of FVIIIR:Ag and FVIIIC to DDAVP stimulus was also found in the patient reported by Ohzeki. In the obligate carriers whom we studied, the FVIIIC response to DDAVP did not significantly differ from that of control subjects, but the FVIIIR:Ag response was significantly reduced in the first carrier (10% of reference values) and was completely absent in the second. On the basis of these results, one can assume NDI to be a heterogeneous illness, at least regarding the FVIII response to DDDAVP stimulus. Caution should therefore be exercised in using the test for identifying carriers or diagnosing the illness.