Lack of desmopressin (DDAVP) response in men with hemophilia A following liver transplantation

Summary.  Although hemophilia A, a congenital disorder caused by defective or deficient factor VIII:C (FVIII), is cured by liver transplantation, the exact site of hepatic FVIII production is unknown. Further, while intracellular co-localization of FVIII and von Willebrand factor (VWF) is required for in vitro FVIII secretion, whether it is required for in vivo FVIII secretion is not known. An ideal setting to study this problem is in individuals with hemophilia A following liver transplantation, as their FVIII is synthesized primarily in hepatic, but not extrahepatic endothelial cells, while VWF is synthesized primarily in extrahepatic vascular endothelium. Following liver transplantation for end-stage liver disease, three hemophilic men showed VWF, but no FVIII response to (DDAVP) infusion. By contrast, both VWF and FVIII increased in a non-hemophilic transplant recipient after DDAVP. These findings support a model in which intracellular co-localization of FVIII and VWF is necessary for in vivo FVIII secretion after DDAVP.     

Desmopressin to Prevent Rapid Sodium Correction in Severe Hyponatremia: A Systematic Review

Background

Hyponatremia is common among inpatients and is associated with severe adverse outcomes such as osmotic demyelination syndrome. Current guidelines recommend serum sodium concentration correction targets of no more than 8 mEq/L per day in patients at high risk of osmotic demyelination syndrome. Desmopressin is recommended to control high rates of serum sodium concentration correction in severe hyponatremia. However, recommendations are based on limited data. The objective of this study is to review current strategies for DDAVP use in severe hyponatremia.

Methods

Systematic literature search of 4 databases of peer-reviewed studies was performed and study quality was appraised.

Results

The literature search identified 17 observational studies with 80 patients. We found 3 strategies for desmopressin administration in hyponatremia: 1) proactive, where desmopressin is administered early based on initial serum sodium concentration; 2) reactive, where desmopressin is administered based on changes in serum sodium concentration or urine output; 3) rescue, where desmopressin is administered after serum sodium correction targets are exceeded or when osmotic demyelination appears imminent. A proactive strategy of desmopressin administration with hypertonic saline was associated with lower incidence of exceeding serum sodium concentration correction targets, although this evidence is derived from a small case series.

Conclusions

Three distinct strategies for desmopressin administration are described in the literature. Limitations in study design and sample size prevent definitive conclusions about the optimal strategy for desmopressin administration to correct hyponatremia. There is a pressing need for better quality research to guide clinicians in managing severe hyponatremia.     

DDAVP nasal spray for treatment of menorrhagia in women with inherited bleeding disorders: a randomized placebo-controlled crossover study

To assess DDAVP (1-deamino-8-d-arginine vasopressin; desmopressin) nasal spray in the management of menorrhagia in patients with inherited bleeding disorders, 39 women (aged 18-50 years) with menorrhagia were recruited and were randomized to start 2 months' therapy with placebo or DDAVP (300 micro g) spray in a double-blind crossover study. Twenty-eight and 24 completed first and second period of treatment, respectively. Menstrual loss was assessed using the pictorial blood assessment chart (PBAC) during each treatment period. The main outcome measure was comparison of PBAC scores following DDAVP and placebo treatments. The safety of DDAVP spray was also assessed by monitoring side-effects. Overall, PBAC scores were significantly lower in the second treatment period than the first (P = 0.01). After adjusting for this differences, mean PBAC scores were slightly lower (mean difference 8; 95% confidence interval of - 15.5 to 31.6) in women receiving DDAVP than when receiving placebo, although this difference was not statistically significant (P = 0.51). In conclusion, although there was an indication that menstrual bleeding was less heavy when women received DDAVP than when receiving placebo, the small sample size meant that this difference was not significant.     

Hermansky-Pudlak syndrome: correction of bleeding time by 1-desamino-8D-arginine vasopressin

The effect of the synthetic vasopressin derivative 1-desamino-8D-arginine vasopressin (DDAVP = desmopressin) on bleeding time was studied in three patients with Hermansky Pudlak syndrome. A good response was observed in this type of storage pool disease. DDAVP might be useful in managing the bleeding disorder found in patients with the Hermansky-Pudlak syndrome.     

The Effect of Intranasal DDAVP on Coagulation and Fibrinolytic Activity in Normal Persons

DDAVP (l-desamino-8-D-arginine vasopressin) was administered intranasally to 20 normal persons and blood was collected at various intervals up to 72 h. Plasma concentrations of VIILC, VIIIR:Ag and fibrinolytic activity were increased by DDAVP with peak levels observed 1 h after the administration. Factors V, IX, XI, XII, XIII, P-APT time, platelets, platelet factor 3, P&P, AT III, α₂AP, fibrinogen and FDP were unchanged by the treatment. No side effects or changes in plasma Na or osmolality were observed. The present data demonstrate the selectivity of the effect of DDAVP on the coagulation system and points towards the possibility of using DDAVP in blood donors to increase plasma contents of factor VIII.     

Effects of DDAVP,a vasopressin analog,on delayed matching behavior in the pigeon

Five pigeons were tested in a delayed matching-to-sample task after receiving an acute injection of DDAVP(1-desamino-8-D-arginine), scopolamine or d-amphetamine. A feeding test also was used to document non-specific drug effects. Scopolamine produced a marked dose-related decrement in accuracy of matching, regardless of delay, indicating that scopolamine impairs both discrimination and short-term memory. Neither DDAVP nor d-amphetamine produced consistent changes in delayed matching. Thus, an experimental model of short-term memory with pigeons did not confirm the findings of others of a positive effect of DDAVP upon cognitive performance in humans.     

去氨加压素在股骨头坏死手术中的应用

目的观察去氨加压素(DDAVP)对股骨头坏死手术中出血及凝血的影响,评价其临床实用价值。方法选择拟行骨瓣移植股骨头重建术或股骨头置换术病人62例,分为用药组及对照组,用药组手术开始前30min将0.3μg/kg的DDAVP稀释于100ml生理盐水中在15min内由静脉输入,对照组输入相同量生理盐水。测量2组病人用药前及用药后1h的血球压积(Hct)、血小板计数(PLT)、凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、纤维蛋白原(Fig)以及手术时间和术中失血总量。结果2组病例PLT、PT及Fig比较无显著性差异(P>0.05),用药组用药前后APTT有显著差异(P<0.05)。出血总量2组间差异显著(P<0.05),用药组出血量明显减少。结论去氨加压素可增强股骨头坏死手术患者的凝血功能,减少术中出血量。     

Evidence for vasopressin V1 receptors of rostrodiencephalic neurons: Iontophoretic studies in the in vivo rat. Responses to oxytocin and to angiotensin

Extracellular recordings were obtained in anaesthetized rats from single neurons located in various structures around the rostral end of the third ventricle, known to harbour integrative neurons sensing deficiencies in and originating corrective responses for water-electrolyte balance. Once arginine vasopressin (AVP) responsive neurons were located, a selective antidiuretic agonist (binding to V2 receptors) and either V1 (presser response related) or V2 (antidiuretic) antagonists were iontophoretically applied. Neurons in this region did not respond to the V2 agonist and only the VI antagonist was able to block the response to AVP. It is assessed that the investigated region has neurons equipped only with receptors of the VI type. Interestingly, a number of these neurons also responded to angiotensin II (All), oxytocin and to blood pressure changes. The integrative neuronal population of parasagittal rostrodiencephalic neurons seem therefore to sense indices of haemodynamic changes including their neuro-hormonal signals within the brain such as All and AVP which bind to V1 (pressor response related) receptors.