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Haemophilia : the Official Journal of... Jul 2018Desmopressin is commonly used to reduce bleeding in patients with mucocutaneous bleeding disorders and is available in both intravenous and intranasal forms. Given the...
INTRODUCTION
Desmopressin is commonly used to reduce bleeding in patients with mucocutaneous bleeding disorders and is available in both intravenous and intranasal forms. Given the variability in response to desmopressin at an individual level, its effectiveness should be assessed with a test dose prior to being advised for use. At this time, no trial has extensively compared the use of intranasal desmopressin to intravenous desmopressin.
AIMS
To determine whether both forms of desmopressin are equally effective in yielding a positive response in laboratory assays in paediatric patients with von Willebrand disease or probable von Willebrand disease.
METHODS
We evaluated medical record data for 58 patients who underwent desmopressin stimulation testing in our haematology clinic during a 1-year period. Data were collected on demographic information and haematologic laboratory assays prior to desmopressin administration and one hour following desmopressin.
RESULTS
There was an absolute increase in von Willebrand antigen to levels appropriate for haemostasis following both forms of desmopressin, although this increase was significantly greater in the intravenous group compared to the intranasal group. There was also a significant absolute increase in Ristocetin Cofactor and Factor VIII levels following desmopressin in both groups.
CONCLUSION
Both intravenous and intranasal forms of desmopressin produce a positive response during desmopressin stimulation testing and can be used to identify patients for whom this medication would be effective.
Topics: Administration, Intranasal; Administration, Intravenous; Child; Deamino Arginine Vasopressin; Female; Humans; Male; Treatment Outcome; von Willebrand Diseases
PubMed: 29578274
DOI: 10.1111/hae.13452 -
Clinical Pharmacokinetics Jan 2021Hemophilia A and B are bleeding disorders caused by a deficiency of clotting factor VIII and IX, respectively. Patients with severe hemophilia (< 0.01 IU mL) and some... (Review)
Review
Hemophilia A and B are bleeding disorders caused by a deficiency of clotting factor VIII and IX, respectively. Patients with severe hemophilia (< 0.01 IU mL) and some patients with moderate hemophilia (0.01-0.05 IU mL) administer clotting factor concentrates prophylactically. Desmopressin (D-amino D-arginine vasopressin) can be applied in patients with non-severe hemophilia A. The aim of administration of factor concentrates or desmopressin is the prevention or cessation of bleeding. Despite weight-based dosing, it has been demonstrated that factor concentrates still exhibit considerable pharmacokinetic variability. Population pharmacokinetic analyses, in which this variability is quantified and explained, are increasingly performed in hemophilia research. These analyses can assist in the identification of important patient characteristics and can be applied to perform patient-tailored dosing. This review aims to present and discuss the population pharmacokinetic analyses that have been conducted to develop population pharmacokinetic models describing factor levels after administration of factor VIII or factor IX concentrates or D-amino D-arginine vasopressin. In total, 33 publications were retrieved from the literature. Two approaches were applied to perform population pharmacokinetic analyses, the standard two-stage approach and non-linear mixed-effect modeling. Using the standard two-stage approach, four population pharmacokinetic models were established describing factor VIII levels. In the remaining 29 analyses, the non-linear mixed-effect modeling approach was applied. NONMEM was the preferred software to establish population pharmacokinetic models. In total, 18 population pharmacokinetic analyses were conducted on the basis of data from a single product. From all available population pharmacokinetic analyses, 27 studies also included data from pediatric patients. In the majority of the population pharmacokinetic models, the population pharmacokinetic parameters were allometrically scaled using actual body weight. In this review, the available methods used for constructing the models, key features of these models, patient population characteristics, and established covariate relationships are described in detail.
Topics: Blood Coagulation Factors; Child; Deamino Arginine Vasopressin; Hemophilia A; Humans
PubMed: 32936401
DOI: 10.1007/s40262-020-00936-5 -
Hematology. American Society of... Dec 2019The management of von Willebrand disease (VWD) is based upon the dual correction of the primary hemostasis defect, due to the inherited deficiency of von Willebrand... (Review)
Review
The management of von Willebrand disease (VWD) is based upon the dual correction of the primary hemostasis defect, due to the inherited deficiency of von Willebrand factor (VWF), and of the secondary defect of factor VIII coagulant activity (FVIII:C), due to the loss of binding and stabilization by VWF of this intrinsic coagulation factor in flowing blood. The traditional therapeutic weapons (the synthetic derivative of the antidiuretic hormone desmopressin and plasma-derived VWF/FVIII concentrates) are able to transiently correct both the defects. With the goal of tackling the primary deficiency in the disease, that is, VWF, but at the same time exploiting the normal capacity of patients to produce FVIII, the novel approach of replacing only VWF was implemented in the last 10 years. Following the manufacturing of a concentrate fractionated from human plasma and of one obtained by recombinant DNA technology, clinical studies have shown that VWF-only products correct not only the primary VWF deficiency but also the secondary FVIII:C deficiency. The demonstrated efficacy of these products in various clinical situations and, ultimately, in such a hemostasis-challenging context as surgery testifies to the effectiveness and safety of this approach. It remains to be seen whether VWF-only products are efficacious and safe in still-unexplored situations, such as use in children; the long-term use for prophylaxis; and in recurrent gastrointestinal (GI) bleeding due to angiodysplasia, a major therapeutic problem in VWD.
Topics: Aged; Deamino Arginine Vasopressin; Factor VIII; Female; Gastrointestinal Hemorrhage; Humans; von Willebrand Diseases; von Willebrand Factor
PubMed: 31808884
DOI: 10.1182/hematology.2019000368 -
Lower Urinary Tract Symptoms Jan 2020This study assessed the efficacy and safety of desmopressin orally disintegrating tablets (ODTs) in Japanese males (50 and 25 μg) and females (25 μg) with nocturia... (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy and safety of 25 and 50 μg desmopressin orally disintegrating tablets in Japanese patients with nocturia due to nocturnal polyuria: Results from two phase 3 studies of a multicenter randomized double-blind placebo-controlled parallel-group development program.
This study assessed the efficacy and safety of desmopressin orally disintegrating tablets (ODTs) in Japanese males (50 and 25 μg) and females (25 μg) with nocturia due to nocturnal polyuria (NP). Two Phase 3 randomized double-blind placebo-controlled studies of 342 males and 190 females with nocturia due to NP were conducted. The primary endpoint was change from baseline in mean number of nocturnal voids. In addition, time to first awakening to void, nocturnal urine volume, NP index (NPI), and quality of life were assessed during a 12-week treatment period. In males, 50 and 25 μg desmopressin ODTs significantly reduced the number of nocturnal voids by -1.21 (P < .0001) and - 0.96 (P = .0143), respectively, and significantly prolonged the time to first awakening to void by 117.60 minutes (P < .0001) and 93.37 minute (P = .0009), respectively, with no safety concerns. In females, 25 μg desmopressin ODT significantly prolonged the time to first awakening to void by 116.11 minutes (P = .0257), with no safety concerns. The reduction in the number of nocturnal voids (-1.11) was not significantly different compared with placebo (P = .0975). Desmopressin ODTs (50 and 25 μg) were an effective and well-tolerated treatment for nocturia due to NP in Japanese males, and desmopressin ODT 50 μg is an appropriate dose in these patients. For patients who are likely to experience hyponatremia, such as elderly males, starting with 25 μg desmopressin ODT should be considered.
Topics: Administration, Oral; Aged; Antidiuretic Agents; Deamino Arginine Vasopressin; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Japan; Male; Middle Aged; Nocturia; Polyuria; Tablets; Treatment Outcome
PubMed: 31397969
DOI: 10.1111/luts.12276 -
Medical Archives (Sarajevo, Bosnia and... Dec 2021One of the common pediatric issues is monosymptomatic nocturnal enuresis (MNE). MNE is involuntarily urine-voiding in night sleep without lower urinary tract symptoms,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
One of the common pediatric issues is monosymptomatic nocturnal enuresis (MNE). MNE is involuntarily urine-voiding in night sleep without lower urinary tract symptoms, such as daytime frequency, incontinence, or urgency. Alarm therapy and desmopressin have been used for treating MNE, but there is no clear comparison of the effectiveness of the two modalities.
OBJECTIVE
This study aimed to compare the efficacy of alarm therapy and desmopressin and strategies to improve the therapy.
METHODS
Study searches were conducted on PubMed, Embase, and Cochrane with a time span of 2010 to 2021. The keywords used were desmopressin, alarm therapy, pediatrics, and monosymptomatic enuresis. The study included an RCT in English, and no subjects were dropped out. Studies without a definite number of subjects were excluded.
RESULTS
As many as 12 studies were included in the meta-analysis, 9 of which looked for response rates, and 3 were for desmopressin-withdrawal optimization strategy. Alarm therapy was superior to desmopressin in well-motivated parents and patients (p=0.02), with a combined risk ratio of 1.10 in the low heterogeneity population (Z-score = 2.31; I = 32%). A strategy that could reduce the risk of desmopressin-withdrawal was a structured dose reduction rather than a sudden dose reduction (p=0.001; I=0%; Z-score = 3.26). However, therapy discontinuation based on time did not differ the risk (p=0.24; I=0%; Z-score = 1.17).
CONCLUSION
The meta-analysis shows that alarm therapy has a better response rate than desmopressin in proactive parents. However, desmopressin may be an option in the opposite subjects, and it is necessary to use structured strategies to optimize the treatment.
Topics: Child; Deamino Arginine Vasopressin; Humans; Nocturnal Enuresis; Urinary Incontinence
PubMed: 35169370
DOI: 10.5455/medarh.2021.75.431-435 -
In Vivo (Athens, Greece) 2023Effect predictors of desmopressin for nocturia associated with nocturnal polyuria are understudied. Herein, we investigated the effects of desmopressin on sleep and...
BACKGROUND/AIM
Effect predictors of desmopressin for nocturia associated with nocturnal polyuria are understudied. Herein, we investigated the effects of desmopressin on sleep and patient quality of life. We defined cases in which administration of desmopressin led to hours of undisturbed sleep (HUS) ≥3 hours as "marked response cases" and examined predictive factors of desmopressin treatment response.
PATIENTS AND METHODS
Our study included 129 patients who were administered desmopressin 50 μg for nocturia associated with nocturnal polyuria at our hospital. Efficacy and safety of desmopressin were examined using bladder diaries, International Prostate Symptom Score, Overactive Bladder Symptom Score, Athens Insomnia Scale, Patient Global Impression of Improvement (PGI-I) score, physical examinations, blood tests, and body composition analyzers, and the predictors of desmopressin efficacy were investigated.
RESULTS
Significant improvements in all endpoints were observed from the early stage onward after desmopressin treatment compared with before treatment. After treatment, HUS was significantly longer in patients with good PGI-I scores, which indicated patient satisfaction. Variation in nocturnal micturition frequency did not affect the improvement in patient satisfaction. Examination of cases defined as "marked response cases" showed that the mean night-time urine volume was an independent predictor of treatment response.
CONCLUSION
Desmopressin can improve patients' quality of life and sleep by extending HUS. This suggests that desmopressin may be effective in patients with high mean night-time urine volumes based on their bladder diary.
Topics: Male; Humans; Nocturia; Polyuria; Deamino Arginine Vasopressin; Antidiuretic Agents; Quality of Life
PubMed: 37905667
DOI: 10.21873/invivo.13383 -
The Cochrane Database of Systematic... Oct 2017Nocturia is the bothersome symptom of awakening one or more times per night to void. Desmopressin is a commonly used medication for treating nocturia. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Nocturia is the bothersome symptom of awakening one or more times per night to void. Desmopressin is a commonly used medication for treating nocturia.
OBJECTIVES
To assess the effects of desmopressin as compared to other interventions in the treatment of nocturia in men.
SEARCH METHODS
We performed a comprehensive search of medical literature with no restrictions on the language of publication or publication status. The date of the latest search of all databases was August 2017.
SELECTION CRITERIA
We included randomized or quasi-randomized trials. Inclusion criteria were men with nocturia defined as one or more voids per night. Trials of children, adults with primary or secondary enuresis or underlying distinct disorders were excluded.
DATA COLLECTION AND ANALYSIS
Two review authors independently classified studies and abstracted data from the included studies. We performed statistical analyses using a random-effects model and interpreted data according to the Cochrane Handbook for Systematic Reviews of Interventions.
MAIN RESULTS
We included 14 studies with 2966 randomized men across five comparisons. Desmopressin versus placebo: based on short-term follow-up (up to three months), desmopressin may have a similar effect on the number of nocturnal voids (mean difference (MD) -0.46, 95% confidence interval (CI) -0.94 to 0.01; low-quality evidence). We are uncertain about the effect of desmopressin on major adverse events at short-term follow-up (risk ratio (RR) 0.97, 95% CI 0.10 to 9.03; very low-quality evidence). For intermediate-term follow-up (three to 12 months), desmopressin may reduce the number of nocturnal voids in an appreciable number of participants (MD -0.85, 95% CI -1.17 to -0.53; low-quality evidence). Desmopressin may result in little or no difference in major adverse events at intermediate-term follow-up (RR 3.05, 95% CI 0.13 to 73.39; low-quality evidence). We found no evidence on quality of life. Subgroup analyses suggest a larger effect with oral, higher-dose formulations of desmopressin and in men with documented nocturnal polyuria. Desmopressin versus behavior modification: there were no data regarding the effect on the number of nocturnal voids, quality of life, or major adverse events. Desmopressin versus alpha-blocker: based on short-term follow-up, desmopressin likely has a similar effect on the number of nocturnal voids (MD 0.30, 95% CI -0.20 to 0.80; moderate-quality evidence) and quality of life (MD 0.00, 95% CI -0.35 to 0.35; moderate-quality evidence). There were no major adverse events in either study group. Desmopressin plus alpha-blocker versus alpha-blocker alone: based on short-term follow-up, combination therapy likely results in a small, unimportant reduction in the number of nocturnal voids (MD -0.47, 95% CI -0.73 to -0.21; moderate-quality evidence) and quality of life (MD -0.29, 95% CI -0.51 to -0.07; moderate-quality evidence). The risk of major adverse events may be similar (RR 0.30, 95% CI 0.01 to 7.32; low-quality evidence). Desmopressin plus alpha-blocker versus alpha-blocker plus an anticholinergic: based on short-term follow-up, combination therapy likely results in little or no difference in the number of nocturnal voids (MD -0.43, 95% CI -0.97 to 0.11; moderate-quality evidence). We found no evidence on quality of life. There were no major adverse events in either study group.
AUTHORS' CONCLUSIONS
Desmopressin may reduce the number of nocturnal voids in an appreciable number of participants compared to placebo in intermediate-term (three to 12 months) follow-up without increase in major adverse events. We found no evidence to compare its effects to behavior modification. The effect on the number of nocturnal voids is likely similar to that of alpha-blockers short-term with very infrequent major adverse events. There appears to be no added benefit in the combined use of desmopressin with an alpha-blocker or an anticholinergic. The findings of this review were limited by short-term follow-up, study limitations, and imprecision.
Topics: Adrenergic alpha-Antagonists; Aged; Antidiuretic Agents; Cholinergic Antagonists; Deamino Arginine Vasopressin; Drug Therapy, Combination; Humans; Male; Middle Aged; Nocturia; Quality of Life; Randomized Controlled Trials as Topic; Withholding Treatment
PubMed: 29055129
DOI: 10.1002/14651858.CD012059.pub2 -
Journal of Pediatric Urology Apr 2024The voiding chart is part of the initial evaluation of enuresis, since the data gathered this way are assumed to carry predictive information. However, there is little...
BACKGROUND
The voiding chart is part of the initial evaluation of enuresis, since the data gathered this way are assumed to carry predictive information. However, there is little evidence that the voiding chart actually does predict therapy response. Lundmark & Nevéus performed a pilot investigation in 2020 and found that anamnestic and voiding chart data did not predict response to second-line therapies. This study aims at evaluating whether these findings could be replicated.
PATIENTS AND METHODS
This is an evaluation of clinical practice. All patients in a tertiary outpatient clinic with enuresis resistant to first-line therapy (i.e. the enuresis alarm and desmopressin medication) during the evaluation period were included in the study. Baseline anamnestic data focused on bladder and bowel habits, were gathered and the families were instructed to complete a voiding chart including measurements of nocturnal urine production. The children were then treated in accordance with international guidelines, which are anticholinergics and antidepressants as second- and third-line treatment, respectively. Desmopressin was added if needed.
RESULTS
In total, 70 patients were included. At the end of the study 37 of these patients were dry, 11 patients were still wetting their beds and 22 patients were lost to follow-up. Of the dry patients 21 became dry on anticholinergics (and/or mirabegron, with or without desmopressin), five on tricyclic antidepressants (with or without desmopressin), seven after a new attempt with the alarm and five became dry spontaneously. The only statistically significant differences between responders and non-responders to the various treatments were that children responsive to anticholinergics had harder and more infrequent stools (p = 0.04 and p = 0.03, respectively).
CONCLUSION
This study found that anamnestic and voiding chart data do not predict response to treatment in children with therapy-resistant enuresis. Because of this and the fact that we lose some children who need our help by demanding that they complete a voiding chart before initiating treatment, we question the use of this instrument in the evaluation of therapy-resistant enuresis.
Topics: Child; Humans; Deamino Arginine Vasopressin; Enuresis; Nocturnal Enuresis; Urinary Bladder; Cholinergic Antagonists
PubMed: 37977907
DOI: 10.1016/j.jpurol.2023.10.036 -
Seminars in Thrombosis and Hemostasis Jul 2016Although in most cases von Willebrand disease (VWD) is a mild disorder, a subgroup of patients experience frequent bleeding. In contrast to severe hemophilia in which... (Review)
Review
Although in most cases von Willebrand disease (VWD) is a mild disorder, a subgroup of patients experience frequent bleeding. In contrast to severe hemophilia in which prophylaxis is the accepted standard of care, this is less frequently used in VWD. Most type 1 VWD patients can be adequately managed with episodic desmopressin and tranexamic acid. In patients with more severe disease, especially those with type 3 VWD, joint bleeds, epistaxis, menorrhagia, and gastrointestinal bleeding are problematic and usually require treatment with von Willebrand factor/factor VIII (VWF/FVIII) concentrate. While in the past these patients were managed with on-demand VWF/FVIII concentrate, several recent reports have demonstrated the value of prophylactic treatment. Despite some uncertainties about the economic impact of treatment of severe VWD, prophylaxis with VWF concentrate should now be considered as the standard of care for the more severe end of the spectrum of affected individuals. The recent introduction of recombinant VWF concentrate is likely to improve the acceptability of prophylaxis in VWD.
Topics: Deamino Arginine Vasopressin; Factor VIII; Humans; Tranexamic Acid; von Willebrand Disease, Type 1; von Willebrand Disease, Type 3; von Willebrand Factor
PubMed: 27253087
DOI: 10.1055/s-0036-1581106 -
Blood Mar 2018Type 2B von Willebrand disease (VWD) is an inherited bleeding disorder caused by changes in von Willebrand factor (VWF) that enhance binding of VWF to GPIb on platelets.... (Review)
Review
Type 2B von Willebrand disease (VWD) is an inherited bleeding disorder caused by changes in von Willebrand factor (VWF) that enhance binding of VWF to GPIb on platelets. Although this disorder is seemingly well defined because of this single molecular defect, in reality type 2B VWD is a clinically heterogeneous disorder that can be difficult to identify and manage. Diagnostic criteria include a history of mucocutaneous bleeding, laboratory studies showing enhanced VWF binding of platelets and/or a 2B VWD genetic variant, and a family history consistent with autosomal dominant inheritance. Thrombocytopenia, although not always present, is common and can be exacerbated by physiologic stressors such as pregnancy. The mainstay of therapy for type 2B VWD is VWF replacement therapy. Adjunct therapies useful in other types of VWD, such as antifibrinolytics, are also used in type 2B VWD. 1-Desamino-8-d-arginine vasopressin (DDAVP) is controversial because of exacerbation of thrombocytopenia, but is, in practice, sometimes used for minor bleeding. Here we review the available evidence and provide 3 clinical cases to illustrate the intricacies of diagnosing type 2B VWD to describe the response to DDAVP and to review complexities and management during pregnancy.
Topics: Antifibrinolytic Agents; Blood Platelets; Deamino Arginine Vasopressin; Humans; Platelet Glycoprotein GPIb-IX Complex; von Willebrand Disease, Type 2; von Willebrand Factor
PubMed: 29378695
DOI: 10.1182/blood-2017-06-742692