deamino-arginine-vasopressin and Hemophilia-B

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

Haemophilia A and B are the most common of the inherited bleeding disorders. Haemophilia in the newborn presents a number of challenges in terms of both diagnosis and management which reflect features unique to this age group. In the presence of a family history of haemophilia optimal management requires close co-operation between three individual specialist groups - obstetricians, haematologists and neonatologists, who each have an important role to play in ensuring a safe outcome for these infants. More problematic is where a family history is absent or has not been adequately elucidated in which case the diagnosis of haemophilia in the neonate will be unsuspected. Diagnostic difficulties may then arise due to failure to recognise the presence of abnormal bleeding, which is often different from that typically observed in older children with haemophilia. In addition, diagnostic investigations are complicated by physiological differences in the neonatal haemostatic system. Although major bleeding is relatively uncommon, the incidence of intracranial haemorrhage is higher during the first few days of life than at any other stage in childhood, which relates to the trauma of delivery. Controversy, however, remains on optimal strategies for both prevention and management of this potentially devastating complication.

Topics: Deamino Arginine Vasopressin; Factor IX; Factor VIII; Hemophilia A; Hemophilia B; Hemorrhage; Hemostatics; Humans; Infant, Newborn; Male; Pedigree; Vitamin K; Vitamin K Deficiency Bleeding

Topics: Combined Modality Therapy; Deamino Arginine Vasopressin; Female; Hemophilia A; Hemophilia B; Humans; Male; Perioperative Nursing; Preoperative Care; Prognosis; Quality of Life; Risk Assessment; Severity of Illness Index; United Kingdom

Over the last 4 decades, there have been very significant advances in the treatment of haemophilia. Plasma products first became available in the 1960s, beginning with cryoprecipitate and then intermediate-purity plasma concentrates, for the treatment of haemophilia A and B. The disasters of viral infections amongst people with haemophilia in the 1980s served to stimulate both the development of techniques of viral inactivation of concentrates and the manufacture of purer products. We therefore now have safe plasma products that are also pure in that they are concentrates of only the deficient protein responsible for the congenital coagulopathy. Preparations of specific coagulation proteins obtained using recombinant biotechnology techniques have been available since 1995. By contrast, pharmacological options for the treatment of the haemophilia remain very limited. The only therapeutic alternatives of real practical value which have been available in the last 30 years for the treatment of haemophilic patients are desmopressin, antifibrinolytic agents, aprotinin, concentrated oestrogens, and local haemostatic agents such as topical thrombin or fibrin glue. This article aims to assess the pharmacological basis and accumulated experience relating to these drugs when used for the prevention and treatment of bleeding in patients with haemorrhagic disorders.

Topics: Antifibrinolytic Agents; Contraindications; Deamino Arginine Vasopressin; Hemophilia A; Hemophilia B; Hemorrhage; Humans

Recent years have witnessed advances in the treatment of haemophilia such as the introduction of prophylaxis, continuous infusion and pharmacological treatment with desmopressin (DDAVP). Prophylactic treatment on a long-term basis appears to be effective in preventing the development of arthropathy in severe haemophilia. The largest body of experience is that from Sweden, where prophylaxis is started at the age of 1-2 years. The dosage used is 25-40 U factor VIII/IX per kilogram bodyweight given three times or twice weekly, respectively. In some cases an intravenous access device has to be used during the first years of treatment. The patients grow up like normal boys and can live virtually normal lives. The beneficial psychological impact of prophylaxis on the family cannot be overestimated. Side-effects are not more frequent with prophylaxis than with on-demand treatment. The feasibility of continuous infusion of factor VIII/IX concentrates during bleeding episodes, or as cover for surgery, has been documented. This mode of delivery increases convenience and the cost-benefit ratio of the treatment, with savings in postoperative replacement of factor concentrate of about 50-75%. Many modern concentrates are stable enough for the purpose, and several pump systems, including portable ones, are available. The haemostatic drug DDAVP can be effectively used in most cases of mild haemophilia A. Intravenous administration is to be preferred as cover for surgery or in the case of severe bleeds. There is an effective nasal spray which can also be used for home therapy in mild or moderate bleedings.

Topics: Adolescent; Catheterization, Central Venous; Catheterization, Peripheral; Child; Child, Preschool; Deamino Arginine Vasopressin; Factor IX; Factor VIII; Female; Hemarthrosis; Hemophilia A; Hemophilia B; Hemorrhage; Hemostatics; Humans; Infant; Infusions, Intravenous; Injections, Intravenous; Male; Practice Guidelines as Topic; Treatment Outcome; World Health Organization

Hemophilias A and B are inherited disorders of clotting-factor production that are characterized by low levels of factor VIII- or IX-coagulant activity. The clinical course of patients with hemophilia is marked by episodes of hemorrhage, some spontaneous and some related to trauma or medical procedures. The physical well-being of patients with hemophilia is maintained by the prevention of bleeding when possible and by prompt, effective treatment of bleeding when it occurs. Factor-replacement therapy continues to be the mainstay of hemophilia treatment, but like pharmacotherapy for other disease states, it is most effective when provided within the framework of a well-designed, individualized therapeutic plan. Currently available factor concentrates have a much greater safety profile than older products, but they are not free of adverse effects. Patients with inhibitors continue to present a challenge in restoring hemostasis. Pharmacists can play an important role in the pharmaceutical care of patients with hemophilia.

Topics: Antifibrinolytic Agents; Deamino Arginine Vasopressin; Factor VIII; Hemophilia A; Hemophilia B; Humans

Haemophilia is a congenital, life-long disorder that may cause major disabilities. The goal of comprehensive care is to prevent problems when possible, to treat early in order to minimize morbidity, and to restore function to disabled patients. The co-ordinated efforts of many experts are needed for success.

Topics: Aminocaproic Acid; Analgesics; Animals; Anti-Inflammatory Agents; Arthritis; Blood Coagulation Factors; Blood Transfusion; Deamino Arginine Vasopressin; Dental Care; Estrogens; Factor IX; Factor IXa; Factor VIII; Hemophilia A; Hemophilia B; Hemorrhage; Humans; Oral Hygiene; Plasma; Progesterone; Self Administration; Surgical Procedures, Operative; Swine; Synovitis

The treatment of haemophilia has been dramatically improved since the introduction of factor VIII and IX concentrates, however these concentrates have brought new problems such as hepatitis and A.I.D.S. An oral agent which could raise endogenous levels of factor VIII and IX would be of great benefit. Danazol, an anabolic steroid, has recently been shown to increase levels of factors VIII and IX in haemophilia. We therefore studied the effect of stanozolol, a closely related anabolic steroid, in 15 patients with haemophilia A or Christmas disease over a 2-4 week period. There was no consistent change in factor VIIIc or factor IX, and fibrinolysis was significantly enhanced. No effect was apparent on the incidence of spontaneous bleeds. However serum aminotransferases which were abnormal in 11 of the 15 patients at the start of the study fell significantly with stanozolol therapy. This raises the interesting possibility that anabolic steroids may be beneficial in patients with chronic liver diseases.

Topics: Blood Viscosity; Clinical Trials as Topic; Deamino Arginine Vasopressin; Factor IX; Factor VIII; Fibrinolysis; Hemophilia A; Hemophilia B; Humans; Kinetics; Male; Stanozolol

Topics: Deamino Arginine Vasopressin; Factor IX; Factor VIII; Hemophilia A; Hemophilia B; Hemostatics; Humans

A guide for the dental management of the three inherited bleeding disorders, von Willebrand's disease, haemophilia A and haemophilia B, was established jointly by the Institute of Medical and Veterinary Science Transfusion and Haemostasis Unit in conjunction with the Medically Compromised Dental Unit at the Adelaide Dental Hospital. This protocol was subjected to a successful trial for 24 months.

Topics: Adolescent; Adult; Aged; Antifibrinolytic Agents; Clinical Protocols; Deamino Arginine Vasopressin; Dental Care for Chronically Ill; Factor IX; Factor VIII; Hemophilia A; Hemophilia B; Hemostatics; Humans; Middle Aged; Oral Hemorrhage; Postoperative Care; Tranexamic Acid; von Willebrand Diseases

Topics: Blood Coagulation Tests; Child; Deamino Arginine Vasopressin; Hemophilia B; Hemostatics; Humans; Male; Tooth Extraction

We tested the response to desmopressin (1-deamino-cys-8-D-arginine-vasopressin; DDAVP) in four patients with haemophilia B [factor IX (F IX) at diagnosis 1.4-5%]. The activated partial thromboplastin time (aPTT) was significantly shortened in all patients. Although there was an up to 1.4-fold increase in F IX levels in three patients, maximal F IX activity remained below 10%. Much more prominent were the increases in F VIII (three- to fourfold), in von Willebrand factor antigen (VWF:Ag; 2.5-fold) and particularly in VWF collagen-binding activity (VWF:CBA; fivefold). These changes were reflected by the prophylactic efficacy of DDAVP for dental surgery. After pretesting, DDAVP could be a useful drug for reducing the need for plasma products for prevention of minor surgical bleeding in patients with mild to moderate haemophilia B.

Topics: Adolescent; Deamino Arginine Vasopressin; Dentistry, Operative; Factor IX; Factor VIII; Hemophilia B; Hemostatics; Humans; Male; Oral Hemorrhage; Partial Thromboplastin Time; Postoperative Hemorrhage; Premedication; von Willebrand Factor

Topics: Blood Transfusion; Contraindications; Deamino Arginine Vasopressin; Emergencies; Factor IX; Factor VIII; Hemophilia A; Hemophilia B; Hemorrhage; Hemostatics; Humans; Male; Risk Factors; Wounds and Injuries

Haemophilia is a rare and complex disorder and its successful management will depend upon the establishment of a network of 'comprehensive care' including the services of haematologists, orthopaedic surgeons, rheumatologists, dental surgeons, physiotherapists, specialised nurses and counsellors. One of the major lessons to be learned from the HIV epidemic in haemophilia is that it is critical to strive to obtain the safest and purest forms of blood products for these patients. The advent of clinically available recombinant factor VIII is expected soon; in the meantime there is a move towards treating all patients with high purity products.

Topics: Cerebral Hemorrhage; Deamino Arginine Vasopressin; Factor IX; Factor VIII; Genetic Counseling; Hemarthrosis; Hemophilia A; Hemophilia B; Humans; Male; Patient Care Team; Prevalence; Transfusion Reaction; Virus Diseases; von Willebrand Diseases

Topics: Deamino Arginine Vasopressin; Factor IX; Factor VIII; Hemophilia A; Hemophilia B; Humans; Mutation; von Willebrand Diseases; von Willebrand Factor

Topics: Adolescent; Adult; Blood Coagulation; Child; Deamino Arginine Vasopressin; Female; Fibrinolysis; Hemophilia A; Hemophilia B; Humans; Male; Middle Aged; Oral Hemorrhage; Tooth Extraction; von Willebrand Diseases; Wound Healing

Of 120 patients presenting with mild bleeding disorders, 63 were found to have a definite coagulopathy. The commonest disorders were haemophilia, Christmas disease and von Willebrand's disease (vWd), the latter being predominant. Diagnosis led to prophylactic treatment prior to surgery in 18 patients with prevention of excessive haemorrhage. Three patients who had received blood products developed hepatitis. DDAVP (desamino-cys-1-8-D-arginine vasopressin) is the treatment of choice in suitable mildly affected patients with haemophilia A and vWd. Examination of blood group distribution suggests an excess of group O among patients with bleeding disorders, especially those with vWd.

Topics: Adult; Arginine Vasopressin; Deamino Arginine Vasopressin; Female; Hemophilia A; Hemophilia B; Hemorrhage; Humans; Male; Middle Aged; Postoperative Complications; Tooth Extraction; von Willebrand Diseases

Topics: Administration, Intranasal; Adolescent; Adult; Arginine Vasopressin; Blood Donors; Child; Deamino Arginine Vasopressin; Factor VIII; Female; Hemophilia A; Hemophilia B; Humans; Injections, Intravenous; Male; Middle Aged; von Willebrand Diseases