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Seminars in Thrombosis and Hemostasis Apr 2017von Willebrand factor (VWF) is an adhesive plasma protein that primarily acts to bridge platelets to sites of vascular injury and thus prevent bleeding. von Willebrand... (Review)
Review
von Willebrand factor (VWF) is an adhesive plasma protein that primarily acts to bridge platelets to sites of vascular injury and thus prevent bleeding. von Willebrand disease (VWD) is the most common inherited bleeding disorder and is caused by deficiency and/or defects of VWF, leading to low levels of plasma VWF or dysfunctional VWF. Factor VIII (FVIII) is also reduced in many patients with VWD, since VWF stabilizes and protects FVIII from degradation. Treatment of VWD primarily entails replacement of VWF, and sometimes FVIII, to protect against bleeding. This may entail use of VWF/FVIII concentrates, and/or desmopressin (1-deamino-8-d-arginine vasopressin) to release endogenous VWF in some patients. Adjunct therapies include antifibrinolytics and hormonal therapies in women. Optimal treatment of VWD entails measuring the effects of treatment, either as a trial before surgery or during therapeutic management. This is usually accomplished by performance of the same tests that are used to help diagnose VWD, although additional monitoring (clinically and/or by laboratory testing) may also be performed. The current review provides an overview of the treatment of VWD but is primarily focused on the monitoring of such therapy.
Topics: Coagulants; Deamino Arginine Vasopressin; Drug Combinations; Drug Monitoring; Factor VIII; Female; Hemostatics; Humans; Menorrhagia; Treatment Outcome; von Willebrand Diseases; von Willebrand Factor
PubMed: 27472426
DOI: 10.1055/s-0036-1585080 -
Pediatric Nephrology (Berlin, Germany) Feb 2017Most patients with monosymptomatic nocturnal enuresis can be effectively treated with an enuresis alarm or antidiuretic therapy (desmopressin), depending on the... (Review)
Review
Most patients with monosymptomatic nocturnal enuresis can be effectively treated with an enuresis alarm or antidiuretic therapy (desmopressin), depending on the pathophysiology of the condition in the individual patient. Desmopressin is first-line therapy for enuresis caused by nocturnal polyuria, an excessive urine output during the night. However, in a recent study, around one-third of patients thought to be resistant to desmopressin were subsequently treated effectively with desmopressin monotherapy in a specialist centre. The aim of this article is to review best practice in selecting patients for desmopressin treatment, as well as outline eight recommendations for maximizing the chances of treatment success in patients receiving desmopressin. The roles of formulation, dose, timing of administration, food and fluid intake, inter-individual variation in response, body weight, adherence, withdrawal strategies and combination therapies are discussed in light of the most recent research on desmopressin and enuresis. Possible reasons for suboptimal treatment response are explored and strategies to improve outcomes in patients for whom desmopressin is an appropriate therapy are presented. Through optimization of the treatment plan in primary and specialist care centres, the hope is that fewer patients with this distressing and often embarrassing condition will experience unnecessary delays in receiving appropriate care and achieving improvements.
Topics: Antidiuretic Agents; Child; Deamino Arginine Vasopressin; Drug Administration Schedule; Female; Humans; Male; Medication Adherence; Nocturnal Enuresis; Treatment Outcome
PubMed: 27071997
DOI: 10.1007/s00467-016-3376-7 -
European Journal of Haematology May 2023Intranasal, subcutaneous, or intravenous desmopressin can be utilized to release von Willebrand Factor and Factor VIII into circulation, enhance platelet adhesion and... (Review)
Review
Intranasal, subcutaneous, or intravenous desmopressin can be utilized to release von Willebrand Factor and Factor VIII into circulation, enhance platelet adhesion and shorten bleeding time. Due to these properties, desmopressin can be effective in controlling bleeding in mild hemophilia A, certain subtypes of von Willebrand disease and in acute bleeding from uremia, end stage renal disease, and liver disease. Its use, however, can be complicated by hyponatremia and rarely arterial thrombotic events. While desmopressin has also been used as a prophylactic blood sparing agent in orthopedic, renal, and hepatic procedures, clinical studies have shown limited benefit in these settings. The purpose of this article is to review the evidence for desmopressin in primary hematologic disorders, discuss its mechanism of action and evaluate its utility as a hemostatic and blood sparing product in various bleeding conditions.
Topics: Humans; Hemostatics; Deamino Arginine Vasopressin; Hemostasis; von Willebrand Diseases; Hemorrhage; von Willebrand Factor
PubMed: 36656570
DOI: 10.1111/ejh.13930 -
Neurocritical Care Feb 2022Desmopressin improves hemostasis through the release of factor VIII, von Willebrand factor, and tissue plasminogen activator, and increases platelet adhesion....
INTRODUCTION
Desmopressin improves hemostasis through the release of factor VIII, von Willebrand factor, and tissue plasminogen activator, and increases platelet adhesion. Neurocritical Care guidelines recommend consideration of desmopressin in antiplatelet-associated intracranial hemorrhage. Studies supporting its use have not evaluated the potential impact of desmopressin on serum sodium levels in patients receiving hypertonic saline therapy. The purpose of this study was to assess the impact of desmopressin on sodium levels and hypertonic saline effectiveness in intracranial hemorrhage.
METHODS
This was a single center retrospective observational chart review. Patients were included in the desmopressin group if they were diagnosed with intracranial hemorrhage, administered desmopressin, and received hypertonic saline infusion. Patients in the hypertonic saline alone group were then matched 1:1 to the patients in the desmopressin group. The primary end point was the effect of desmopressin on reaching a sodium goal of 145-155 mEq/L. The secondary end points included intensive care unit and hospital length of stay, change in sodium, time to reach sodium goal, thrombotic events, mortality, and a composite of increased cerebral edema, hematoma expansion, midline shift, herniation, need for neurosurgical intervention, and neurologic decompensation.
RESULTS
Of 112 patients screened, 25 patients met inclusion criteria for the desmopressin group, and 25 patients were matched with patients in the hypertonic saline alone group. The percentage of patients who reached goal sodium in the desmopressin group compared with hypertonic saline alone was similar (80% vs. 88%, respectively). There were no differences in the secondary end points. In the subgroup analysis, patients in the hypertonic saline group met the predefined sodium goal of 150-155 mEq/L within 48 h more often than those in the desmopressin group (82% vs. 60%, respectively, p = 0.042).
CONCLUSIONS
The use of desmopressin in intracranial hemorrhage does not appear to negatively impact the ability for patients to reach goal sodium of 145-155 mEq/L. However, in patients with higher sodium goals, desmopressin may decrease hypertonic saline effectiveness.
Topics: Deamino Arginine Vasopressin; Humans; Intracranial Hemorrhages; Retrospective Studies; Saline Solution, Hypertonic; Tissue Plasminogen Activator
PubMed: 34235613
DOI: 10.1007/s12028-021-01277-2 -
Paediatric Drugs Aug 2020Desmopressin is a synthetic analogue of the natural antidiuretic hormone arginine vasopressin. Over the years, it has been clinically used to manage nocturnal polyuria... (Review)
Review
Desmopressin is a synthetic analogue of the natural antidiuretic hormone arginine vasopressin. Over the years, it has been clinically used to manage nocturnal polyuria in children with enuresis. Various pharmaceutical formulations of desmopressin have been commercialized for this indication-nasal spray, nasal drops, oral tablet and oral lyophilizate. Despite the fact that desmopressin is a frequently prescribed drug in children, its use and posology is based on limited pediatric data. This review provides an overview of the current pediatric pharmacological data related to the different desmopressin formulations, including their pharmacokinetics, pharmacodynamics and adverse events. Regarding the pharmacokinetics, a profound food effect on the oral bioavailability was demonstrated as well as different plasma concentration-time profiles (double absorption peak) of the desmopressin lyophilizate between adults and children. Literature about maturational differences in distribution, metabolism and excretion of desmopressin is rather limited. Regarding the pharmacodynamics, formulation/dose/food effect and predictors of response were evaluated. The lyophilizate is the preferred formulation, but the claimed bioequivalence in adults (200 µg tablet and 120 µg lyophilizate), could not be readily extrapolated to children. Prescribing the standard flat-dose regimen to the entire pediatric population might be insufficient to attain response to desmopressin treatment, whereby dosing schemes based on age and weight were proposed. Moreover, response to desmopressin is variable, whereby complete-, partial- and non-responders are reported. Different reasons were enumerated that might explain the difference in response rate to desmopressin observed: different pathophysiological mechanisms, bladder capacity and other predictive factors (i.e. breast feeding, familial history, compliance, sex, etc.). Also, the relapse rate of desmopressin treatment was high, rendering it necessary to use a pragmatic approach for the treatment of enuresis, whereby careful consideration of the position of desmopressin within this treatment is required. Regarding the safety of the different desmopressin formulations, the use of desmopressin was generally considered safe, but additional measures should be taken to prevent severe hyponatremia. To conclude the review, to date, major knowledge gaps in pediatric pharmacological aspects of the different desmopressin formulations still remain. Additional information should be collected about the clinical relevance of the double absorption peak, the food effect, the bioequivalence/therapeutic equivalence, the pediatric adapted dosing regimens, the study endpoints and the difference between performing studies at daytime or at nighttime. To fill in these gaps, additional well designed pharmacokinetic and pharmacodynamic studies in children should be performed.
Topics: Antidiuretic Agents; Child; Deamino Arginine Vasopressin; Enuresis; Humans; Tablets
PubMed: 32507959
DOI: 10.1007/s40272-020-00401-7 -
Investigative and Clinical Urology Sep 2022Nocturia is the most bothersome of lower urinary tract symptoms in men. Desmopressin, a synthetic analog of the human hormone vasopressin, has been used for the... (Review)
Review
PURPOSE
Nocturia is the most bothersome of lower urinary tract symptoms in men. Desmopressin, a synthetic analog of the human hormone vasopressin, has been used for the treatment of nocturia. However, the guidelines include varying recommendations for the use of desmopressin for the management of nocturia in men. Therefore, the Korean Urological Association (KUA) developed recommendations for desmopressin for the treatment of nocturia in men.
MATERIALS AND METHODS
A rigorous systematic review was performed and Grading of Recommendations, Assessment, Development, and Evaluation methodology was used to rate the certainty of evidence for patient outcomes and to develop the evidence into recommendations. The steering group, guidelines development group, systematic review team, and external review group consisted of members of the Korean Continence Society, Korean Society of Geriatric Urological Care, and KUA, respectively, who were involved in the guidelines development process.
RESULTS
The guidelines address the benefits, harms, patients' values and preferences, costs, and resources related to desmopressin by using a single clinical question: What is the effectiveness of desmopressin compared to that of placebo, behavior modification, or other pharmacological therapies?
CONCLUSIONS
The guidelines development panel suggests desmopressin for men with nocturia instead of placebo, behavior modification, or alpha-blocker monotherapy (low certainty of evidence, weak recommendation). Additionally, the panel suggests desmopressin combination therapy with alpha-blockers for men with nocturia instead of alpha-blocker monotherapy or alpha-blocker combination therapy with anticholinergic agents (low certainty of evidence, weak recommendation).
Topics: Adrenergic alpha-Antagonists; Aged; Deamino Arginine Vasopressin; Humans; Lower Urinary Tract Symptoms; Male; Nocturia; Republic of Korea; Treatment Outcome
PubMed: 36067995
DOI: 10.4111/icu.20220165 -
Annales D'endocrinologie Jun 2016Diabetes insipidus (DI) is a rare complication of pregnancy. It is usually transient, being due to increased placental production of vasopressinase that inactivates... (Review)
Review
Diabetes insipidus (DI) is a rare complication of pregnancy. It is usually transient, being due to increased placental production of vasopressinase that inactivates circulating vasopressin. Gestational, transient DI occurs late in pregnancy and disappears few days after delivery. Acquired central DI can also occur during pregnancy, for example in a patient with hypophysitis or neuroinfundibulitis during late pregnancy or postpartum. Finally, pre-existing central or nephrogenic DI may occasionally be unmasked by pregnancy. Treatment with dDAVP (desmopressin, Minirin(®)) is very effective on transient DI of pregnancy and also on pre-existing or acquired central DI. Contrary to vasopressin, dDAVP is not degraded by vasopressinase. Nephrogenic DI is insensitive to dDAVP and is therefore more difficult to treat during pregnancy if fluid intake needs to be restricted.
Topics: Deamino Arginine Vasopressin; Diabetes Insipidus; Diabetes Insipidus, Neurogenic; Female; Humans; Pregnancy; Pregnancy Complications; Vasopressins
PubMed: 27172867
DOI: 10.1016/j.ando.2016.04.005 -
Therapeutic Drug Monitoring Apr 2019Hemophilia A and hemophilia B are hereditary bleeding disorders, caused by a deficiency of clotting factor VIII or clotting factor IX, respectively. To treat and prevent... (Review)
Review
Hemophilia A and hemophilia B are hereditary bleeding disorders, caused by a deficiency of clotting factor VIII or clotting factor IX, respectively. To treat and prevent bleedings, patients can administer clotting factor concentrates (hemophilia A and B) or desmopressin (hemophilia A). Both clotting factor concentrates and desmopressin are currently dosed according to the patients' body weight. However, clotting factor concentrates exhibit considerable pharmacokinetic (PK) variability. Therefore, several alternative dosing strategies to individualize dosing of clotting factor concentrates and desmopressin in hemophilia A and B have been proposed. In this study, a review of the existing literature on the individualization of dosing based on PK guidance was performed. In total, 79 articles were included. The methods to individualize dosing were divided into 3 categories: (1) methods using clinical parameters, (2) empirical individual PK-guided methods, and (3) maximum a posteriori (MAP) Bayesian estimation methods. The clinical parameter mainly used to individualize dosing is bleeding phenotype. Dosing based on bleeding phenotype may decrease clotting factor consumption. However, with this method, it is not possible to individualize on-demand dosing during bleeding events or in the perioperative setting. Empirical individual PK-guided methods can be used both for prevention and treatment of bleedings. These methods include dose individualization using a nomogram and individualized in vivo recovery. In the perioperative setting, adjustment of the rate of continuous infusion can be applied to obtain a specific target level. The final category, MAP Bayesian estimation methods, relies on the availability of a population PK model. In total, 22 population PK models describing clotting factor concentrate or desmopressin dosing are currently available in literature. MAP Bayesian estimates can be used to calculate the individualized doses required to achieve or maintain a target level in every setting. The application of PK-guided and pharmacodynamic-guided dosing of clotting factor concentrates and desmopressin seems promising, although further investigation is warranted. Prospective studies analyzing its potential benefit are on the way.
Topics: Blood Coagulation Factors; Deamino Arginine Vasopressin; Hemophilia A; Hemophilia B; Humans; Precision Medicine
PubMed: 30883513
DOI: 10.1097/FTD.0000000000000625 -
Neurourology and Urodynamics Jan 2024Evidence on the efficacy of desmopressin in nocturia in patients with neurological diseases is still very limited except for multiple sclerosis (MS). Our aim was to... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Evidence on the efficacy of desmopressin in nocturia in patients with neurological diseases is still very limited except for multiple sclerosis (MS). Our aim was to evaluate the efficacy and safety of desmopressin treatment on nocturia in patients with underlying neurological diseases.
METHODS
Studies were identified by electronic search of PubMed, Embase, Cochrane, CINAHL, and Google Scholar databases. Studies were considered if they provided information on the effectiveness and safety of desmopressin (1-desamino-8-d-arginine vasopressin, or DDAVP) in the treatment of nocturia and their participants had acquired neurological pathology. Two researchers independently extracted the articles using specified datasets, such as quality-of-study indicators. Statistical meta-analysis was carried out using Review Manager (RevMan) 5.4 statistical software (Cochrane Collaboration).
RESULTS
Of a total of 1042 articles in the initial search, 14 studies were included. Most of the published papers were related to MS (n = 7), two were on spinal cord injury, and other conditions were neural tube defect, myelodysplasia, Parkinson's disease, stroke, and multiple system atrophy. Overall, a total of 200 patients (mostly females) were enrolled. Thirteen studies evaluated the intranasal formulation of desmopressin and one study evaluated oral desmopressin. A significant decrease in nocturia episodes was reported in seven studies evaluating this topic. An increase in the maximum hours of uninterrupted sleep was reported in the three studies in which this outcome was assessed. A significant reduction in the volume of nocturnal incontinence was found in one study. Three studies were eligible to include in the meta-analysis. The results showed that desmopressin compared to placebo, significantly reduced nighttime urination (mean difference: -0.75, 95% CI: -1.10 to -0.41; p < 0.00001). The rate of adverse events ranged from 0% to 68.42%. The critical appraisal results for all trials showed that most of the studies had low or moderate quality.
CONCLUSIONS
Our results emphasized desmopressin's safety and efficacy in reducing nocturia episodes, with transient adverse effects on neurological patients. However, the data were achieved from low or medium-quality trials, and further well-designed randomized controlled trials are needed.
Topics: Female; Humans; Male; Nocturia; Deamino Arginine Vasopressin; Polyuria; Antidiuretic Agents; Treatment Outcome; Multiple Sclerosis
PubMed: 37746880
DOI: 10.1002/nau.25291 -
Drug and Therapeutics Bulletin Feb 2020Topics for DTB review articles are selected by DTB's editorial board to provide concise overviews of medicines and other treatments to help patients get the best care.... (Review)
Review
Topics for DTB review articles are selected by DTB's editorial board to provide concise overviews of medicines and other treatments to help patients get the best care. Articles include a summary of key points and a brief overview for patients. Articles may also have a series of multiple choice CME questions.
Topics: Age Factors; Antidepressive Agents, Tricyclic; Clinical Alarms; Comorbidity; Deamino Arginine Vasopressin; Humans; Muscarinic Antagonists; Nocturnal Enuresis
PubMed: 32001450
DOI: 10.1136/dtb.2018.000034