Use of desmopressin (DDAVP) during early pregnancy in factor VIII–deficient women

Desmopressin (DDAVP) is being used with caution in the first 2 trimesters of pregnancy in women with bleeding disorders^1,2  because there is concern that the compound may cause placental insufficiency due to arterial vasoconstriction and increase the risks of miscarriage due to an oxytocic effect and to maternal and/or neonatal hyponatremia.³  The latter concern is in principle justified because desmopressin is a potent antidiuretic nonapeptide that acts thorough V2 vasopressin receptors.⁴  On the other hand, its potential for vasoconstriction and uterus contraction is negligible because the compound is practically devoid of these biologic activities related to the activation of V1 vasopressin receptors.⁴  Evidence of its safety during pregnancy in women with diabetes insipidus is available.³  Since the original description of its use for the treatment of mild hemophilia and von Willebrand disease (VWD),⁵  between 1988 and 2002 we used desmopressin in 32 pregnant women with low factor VIII levels in order to improve hemostasis at the time of invasive procedures.

Of 32 pregnant women, 27 were obligatory carriers of hemophilia with factor VIII deficiency, presumably due to extreme random inactivation of their normal X chromosome (lyonization), and 5 had type 1 VWD. Twenty women underwent chorionic villus sampling at gestational weeks 11 to 12 for prenatal diagnosis of hemophilia, the remaining 12 underwent amniocentesis at weeks 16 to 18 for prenatal diagnosis (7 hemophilia carriers) or karyotyping (5 women with type 1 VWD). In all women, factor VIII levels were low enough to engender an increased risk of bleeding (median value, 18 U/dL; range, 10-35 U/dL) and hence to justify the coverage of the procedure with a hemostatic agent. In 22 cases the treatment schedule was based upon the use of a single intravenous infusion of 0.3 μg/kg before the procedure because factor VIII levels attained after infusion were judged sufficient to avoid secondary bleeding. In the remaining 10 cases the same dose was repeated 2 to 3 times at intervals of 18 to 24 hours because factor VIII levels were not sufficient for hemostasis. No laboratory test other than factor VIII assays was carried out after desmopressin because this is the protocol routinely followed in our treated patients with mild hemophilia and VWD. As usual, however, women were advised to avoid excessive fluid intake and to control that their body weights did not increase. Sixty minutes after the infusion, factor VIII levels increased in average 3 times (median, 60 U/dL; range, 40-121 U/dL). In all 32 women there was no abnormal bleeding and in 20 of them pregnancies went successfully to term with the delivery of healthy newborns. In the remaining 12 cases, male fetuses affected by hemophilia on genotyping were aborted under coverage with additional doses of desmopressin. There was no side effect in the treated women other than mild facial flushing and headache and no significant increase in body weight.

This series shows that desmopressin can be used during the first and second trimester of pregnancy and that it is safe during invasive procedures that increase per se the risk of miscarriage. Electrolytes and osmolality were not measured because this is our routine protocol. However, there was no clinical sign of water intoxication or body weight increase in these women, who were warned to restrict fluid intake.