deamino-arginine-vasopressin and Menorrhagia

Unclassified bleeding disorders account for 2.6% of all new bleeding disorder registrations in the UK. The management of the bleeding phenotype associated with these disorders is poorly described. Systematic review and meta-analysis to determine the bleeding rates associated with tranexamic acid, desmopressin, platelet transfusion, plasma transfusion and recombinant activated factor VII, for patients with unclassified bleeding disorders undergoing surgery, childbirth or with menorrhagia. We searched for randomized controlled trials in MEDLINE, Embase, The Cochrane Central Register of Controlled Trials, PubMed, ISI Web of Science and the Transfusion Evidence Library from inception to 24 February 2020. Wherever appropriate, data were pooled using the metaprop function of STATA. Two studies with 157 participants with unclassified bleeding disorders were identified. The pooled risk of minor bleeding for patients undergoing surgery treated with peri-operative tranexamic acid was 11% (95% confidence interval 3--20%; n = 52; I2 = 0%); the risk for desmopressin and tranexamic acid in combination was 3% (95% confidence interval 0--7%; n = 71; I2 = 0%). There were no instances of major bleeding. In one procedure, 1 of 71 (1.4%), treated with a combination of desmopressin and tranexamic acid, the patient had a line-related deep vein thrombosis. There were too few patients treated to prevent postpartum haemorrhage or for menorrhagia to draw conclusions. The GRADE quality of evidence was very low suggesting considerable uncertainty over the results. However, both tranexamic acid, and the combination of tranexamic and desmopressin have high rates of haemostatic efficacy and have few adverse events.. PROSPERO CRD42020169727.

Topics: Antifibrinolytic Agents; Blood Component Transfusion; Deamino Arginine Vasopressin; Disease Management; Female; Hemorrhage; Hemorrhagic Disorders; Hemostatics; Humans; Menorrhagia; Postoperative Hemorrhage; Postpartum Hemorrhage; Pregnancy; Tranexamic Acid

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

von Willebrand disease (VWD) is the most common congenital bleeding disorder. In women, menorrhagia is the most common bleeding symptom, and is disabling with iron deficiency anaemia, high health cost and poor quality of life. Current hormonal and non-hormonal therapies are limited by ineffectiveness and intolerance. Few data exist regarding von Willebrand factor (VWF), typically prescribed when other treatments fail. The lack of effective therapy for menorrhagia remains the greatest unmet healthcare need in women with VWD. Better therapies are needed to treat women with menorrhagia.. We conducted a survey of US haemophilia treatment centres (HTCs) and a literature review using medical subject heading (MeSH) search terms 'von Willebrand factor,' 'menorrhagia' and 'von Willebrand disease' to assess the use of VWF in menorrhagia. Analysis was by descriptive statistics.. Of 83 surveys distributed to HTC MDs, 20 (24.1%) provided sufficient data for analysis. Of 1321 women with VWD seen during 2011-2014, 816 (61.8%) had menorrhagia, for which combined oral contraceptives, tranexamic acid and desmopressin were the most common first-line therapies for menorrhagia, whereas VWF was third-line therapy reported in 13 women (1.6%). Together with data from 88 women from six published studies, VWF safely reduced menorrhagia in 101 women at a dose of 33-100 IU kg(-1) on day 1-6 of menstrual cycle.. This represents the largest VWD menorrhagia treatment experience to date. VWF safely and effectively reduces menorrhagia in women with VWD. A prospective clinical trial is planned to confirm these findings.

Topics: Antifibrinolytic Agents; Contraceptives, Oral; Databases, Factual; Deamino Arginine Vasopressin; Female; Humans; Menorrhagia; Tranexamic Acid; von Willebrand Diseases; von Willebrand Factor

Heavy menstrual bleeding without an organic lesion is mainly due to an imbalance of the various hormones which have a regulatory effect on the menstrual cycle. Another cause of heavy menstrual bleeding with no pelvic pathology, is the presence of an acquired or inherited bleeding disorder. The haemostatic system has a central role in controlling the amount and the duration of menstrual bleeding, thus abnormally prolonged or profuse bleeding does occur in most women affected by bleeding disorders. Whereas irregular, pre-menarchal or post-menopausal uterine bleeding is unusual in inherited or acquired haemorrhagic disorders, severe acute bleeding and heavy menstrual bleeding at menarche and chronic heavy menstrual bleeding during the entire reproductive life are common. This is an update of a previously published Cochrane Review.. To determine the efficacy and safety of non-surgical interventions versus each other, placebo or no treatment for reducing menstrual blood loss in women with bleeding disorders.. We searched the Cochrane Cystic Fibrosis Haemoglobinopathies Trials Register (25 August 2016), Embase (May 2013), LILACS (February 2013) and the WHO International Clinical Trial registry (February 2013).. Randomised controlled studies of non-surgical interventions for treating heavy menstrual bleeding (menorrhagia) in women of reproductive age suffering from a congenital or acquired bleeding disorder.. Two authors independently assessed studies for inclusion, extracted data and assessed the risk of bias.. Three cross-over studies, with 175 women were included in the review. All three studies had an unclear risk of bias with regards to trial design and overall, the quality of evidence generated was judged to be poor.Two of the studies (n = 59) compared desmopressin (1-deamino-8-D-arginine vasopressin) with placebo. Menstrual blood loss was the primary outcome for both of these studies. Neither study found clear evidence of a difference between groups. The first of these reported a mean difference in menstrual blood loss in the desmopressin versus placebo group of 21.20 mL (95% confidence interval -19.00 to 61.50)The second study reported that even though there was an improvement of pictorial bleeding assessment chart scores with desmopressin and placebo when compared to pretreatment assessment, there was no clear evidence of difference in these scores when the two were compared to each other (results presented graphically, P = 0.51). The data from these studies could not be combined.The third study (n = 116) compared desmopressin with tranexamic acid (n = 116). This study found a decrease in pictorial bleeding assessment chart scores after both treatments as compared to baseline. The decrease in these scores was greater for tranexamic acid than for desmopressin, with a mean difference of 41.6 mL (95% confidence interval 19.6 to 63) (P < 0.0002).In relation to adverse events, across two studies, there was no clear evidence of a difference when placebo was compared to desmopressin, risk ratio 1.17 (95% confidence interval 0.41 to 3.34) . The same was also true when desmopressin was compared to tranexamic acid, risk ratio 1.17 (95% confidence interval 0.41 to 3.34).Only the study that compared desmopressin to tranexamic acid assessed quality of life. However, we are unable to present any data from this study, since no differences in this outcome between the two intervention groups were reported.. Evidence from randomised controlled studies on the effect of desmopressin when compared to placebo in reducing menstrual blood loss is very limited and inconclusive. Two studies, each with a very limited number of participants, have shown uncertain effects in menstrual blood loss and adverse effects. A non-randomised comparison in one of the studies points to the value of combining desmopressin and tranexamic acid, which needs to be tested in a formal randomised controlled study comparison.When tranexamic acid was compared to desmopressin, a single study showed a reduction in menstrual blood loss with tranexamic acid use compared to desmopressin.There is a need to evaluate non-surgical methods for treating of menorrhagia in women with bleeding disorders through randomised controlled studies. Such methods would be more acceptable than surgery for women wishing to retain their fertility. Given that women may need to use these treatments throughout their entire reproductive life, long-term side-effects should be evaluated.

Topics: Adult; Blood Coagulation Disorders; Deamino Arginine Vasopressin; Female; Hemostatics; Humans; Menorrhagia; Randomized Controlled Trials as Topic; Tranexamic Acid

Topics: Age Factors; Algorithms; Deamino Arginine Vasopressin; Female; Hemorrhage; Humans; Male; Menorrhagia; von Willebrand Diseases; von Willebrand Factor

Treatment of mucosal bleeding (epistaxis, gastrointestinal bleeding, and menorrhagia) and joint bleeding remains problematic in clinically severe von Willebrand disease (VWD). Patients are often unresponsive to treatment (e.g. desmopressin or antifibrinolytic therapy) and may require von Willebrand factor (VWF) replacement therapy. There are little data on the use of prophylaxis in VWD, and none have been applied in a prospective, treatment escalation design.. Evaluate the effect of escalating dose prophylaxis in severe VWD.. Patients eligible for enrollment in this prospective study included those with type 1 VWD with VW factor activity-ristocetin cofactor ratio ≤ 20% and unresponsive to desmopressin, patients with type 2 VWD not responsive to desmopressin and all subjects with type 2B and type 3 VWD. Entry criteria were strictly defined, as were therapy escalation parameters and clinical data collection.. Eleven subjects completed the study. Six had type 2A, and five had type 3 VWD. Six patients presented with epistaxis, three with GI bleeding, and two with joint bleeding. Seven had dose escalation above the first level. Among the 10 subjects with evaluable bleeding log data, use of prophylaxis decreased the median annualized bleeding rate from 25 to 6.1 (95% confidence interval of the rate difference: -51.6 to -1.7), and the median annualized bleeding rate was even lower (4.0; 95% confidence interval: -57.5 to -5.3) when the subjects reached their final dosing level.. This is the first prospective study to demonstrate that prophylaxis with VW factor concentrates is highly effective in reducing mucosal and joint bleeding rates in clinically severe VWD.

Topics: Blood Loss, Surgical; Blood Transfusion; Clinical Trials as Topic; Deamino Arginine Vasopressin; Drug Administration Schedule; Factor VIII; Female; Hemarthrosis; Hemorrhage; Hospitalization; Humans; Male; Menorrhagia; Multicenter Studies as Topic; Postoperative Hemorrhage; Prospective Studies; Recombinant Proteins; Retrospective Studies; von Willebrand Diseases; von Willebrand Factor

Heavy menstrual bleeding without an organic lesion is mainly due to an imbalance of the various hormones which have a regulatory effect on the menstrual cycle. Another cause of heavy menstrual bleeding with no pelvic pathology, is the presence of an acquired or inherited bleeding disorder. The haemostatic system has a central role in controlling the amount and the duration of menstrual bleeding, thus abnormally prolonged or profuse bleeding does occur in most women affected by bleeding disorders. Whereas irregular, pre-menarchal or post-menopausal uterine bleeding is unusual in inherited or acquired haemorrhagic disorders, severe acute bleeding and heavy menstrual bleeding at menarche and chronic heavy menstrual bleeding during the entire reproductive life are common.. To determine the efficacy and safety of non-surgical interventions versus each other, placebo or no treatment for reducing menstrual blood loss in women with bleeding disorders.. We searched the Cochrane Cystic Fibrosis Haemoglobinopathies Trials Register (13 March 2014), Embase (May 2013), LILACS (February 2013) and the WHO International Clinical Trial registry (February 2013).. Randomised controlled studies of non-surgical interventions for treating heavy menstrual bleeding (menorrhagia) in women of reproductive age suffering from a congenital or acquired bleeding disorder.. Two authors independently assessed studies for inclusion, extracted data and assessed the risk of bias.. Three cross-over studies, with 175 participants were included in the review. All three studies had an unclear risk of bias with regards to trial design and overall, the quality of evidence generated was judged to be poor.Two of the studies (n = 59) compared desmopressin (1-deamino-8-D-arginine vasopressin) with placebo. Menstrual blood loss was the primary outcome for both of these studies. Neither study found clear evidence of a difference between groups. The first of these reported a mean difference in menstrual blood loss in the desmopressin versus placebo group of 21.20 mL (95% confidence interval -19.00 to 61.50)The second study reported that even though there was an improvement of pictorial bleeding assessment chart scores with desmopressin and placebo when compared to pretreatment assessment, there was no clear evidence of difference in these scores when the two were compared to each other (results presented graphically, P = 0.51). The data from these studies could not be combined.The third study (n = 116) compared desmopressin with tranexamic acid (n = 116). This study found a decrease in pictorial bleeding assessment chart scores after both treatments as compared to baseline. The decrease in these scores was greater for tranexamic acid than for desmopressin, with a mean difference of 41.6 mL (95% confidence interval 19.6 to 63) (P < 0.0002).In relation to adverse events, across two studies, there was no clear evidence of a difference when placebo was compared to desmopressin, risk ratio 1.17 (95% confidence interval 0.41 to 3.34) . The same was also true when desmopressin was compared to tranexamic acid, risk ratio 1.17 (95% confidence interval 0.41 to 3.34).Only the study that compared desmopressin to tranexamic acid assessed quality of life. However, we are unable to present any data from this study, since no differences in this outcome between the two intervention groups were reported.. Evidence from randomised controlled studies on the effect of desmopressin when compared to placebo in reducing menstrual blood loss is very limited and inconclusive. Two studies, each with a very limited number of participants, have shown uncertain effects in menstrual blood loss and adverse effects. A non-randomised comparison in one of the studies points to the value of combining desmopressin and tranexamic acid, which needs to be tested in a formal randomised controlled study comparison.When tranexamic acid was compared to desmopressin, a single study showed a reduction in menstrual blood loss with tranexamic acid use compared to desmopressin.There is a need to evaluate non-surgical methods for treating of menorrhagia in women with bleeding disorders through randomised controlled studies. Such methods would be more acceptable than surgery for women wishing to retain their fertility. Given that women may need to use these treatments throughout their entire reproductive life, long-term side-effects should be evaluated.

Topics: Adult; Blood Coagulation Disorders; Deamino Arginine Vasopressin; Female; Hemostatics; Humans; Menorrhagia; Randomized Controlled Trials as Topic; Tranexamic Acid

The haemostatic system has a central role in controlling the amount and the duration of menstrual bleeding, thus abnormally prolonged or profuse bleeding does occur in most women affected by inherited bleeding disorders. Whereas irregular, premenarchal or postmenopausal uterine bleeding is unusual in inherited or acquired heamorrhagic disorders, severe acute bleeding and menorrhagia at menarche and chronic menorrhagia during the entire reproductive life are common manifestations. Prevalence and morbidity of menorrhagia in inherited bleeding disorders have been poorly investigated. It can be estimated that 40% to 60% of currently menstruating women with type 1 or 2 and more than 60% of women with type 3 VWD complain of menorrhagia with a significant impact on their quality of life. Menorrhagia may be particularly distressing in adolescents because of their delicate emotional equilibrium. Similar epidermiology has been described in other inherited disorders like factor XI deficiency, platelet functional defects and in carriers of haemophilia A and B. Women presenting with ''isolated'' menorrhagia, that is without significant additional bleeding symptoms, a situation reported by up to 15% of healthy women, do not demand investigation to exclude an occult bleeding disorder. A multidisciplinary approach is required for diagnosis and treatment. Gynaecological supervision is always required to exclude organic causes unmasked by the bleeding disorder. Treatment options are similar to those for menorrhagia in general with the addition of desmopressin and replacement therapy and the exclusion of non-steroidal anti-inflammatory drugs. The therapeutic plan should take into consideration the patient's preferences, age and severity of bleeding. Iron supplementation is of paramount importance. Remedies used in clinical practice for menorrhagia in general (tranexamic acid, combined oral contraceptives [COC], levonorgestrel intrauterine system [LNG-IUS]) are first tried. In case of failure or contraindication (COC and LNG-IUS are best avoided in adolescents), before considering surgical options, treatment with desmopressin becomes the preferred choice in patients known to be responsive. The availability of desmopressin preparations for self-administration makes home treatment feasible in well selected cases. The treatment is efficacious and safe provided that patients are instructed to self-administer the agent only during the first two or three more heavy days of menstru

Topics: Deamino Arginine Vasopressin; Female; Hemostatics; Humans; Menorrhagia; von Willebrand Diseases

The first part of this benefit-risk review examined the efficacy and adverse effect profiles of systemic haemostatic agents commonly used in major surgery. The second part of this review examines the efficacy and adverse effect profiles of systemic haemostatic agents commonly used in the treatment of excessive or heavy menstrual bleeding, and provides individual benefit-risk profiles that may assist clinicians in selecting appropriate pharmacological therapy in this setting. Historically, surgery has played a dominant role in treatment; however, pharmacological therapy is increasingly popular, especially in women who wish to retain their fertility. When selecting the appropriate treatment, patient preference should be considered, as well as the benefits and risks associated with each agent. Recommended pharmacological therapies that are effective and generally well tolerated include the levonorgestrel-releasing intrauterine system and the oral agents tranexamic acid, NSAIDs (e.g. mefenamic acid) and combined estrogen/progestogen oral contraceptives. In patients with an underlying bleeding disorder (e.g. von Willebrand disease), an additional option is intranasal desmopressin.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Contraceptives, Oral, Combined; Danazol; Deamino Arginine Vasopressin; Female; Gonadotropin-Releasing Hormone; Hemostatics; Humans; Intrauterine Devices, Medicated; Levonorgestrel; Menorrhagia; Progestins; Risk Assessment; Tranexamic Acid

Topics: Antifibrinolytic Agents; Blood Coagulation Tests; Contraceptives, Oral; Deamino Arginine Vasopressin; Diagnosis, Differential; Female; Hemostatics; Humans; Incidence; Menorrhagia; Platelet Function Tests; Prevalence; von Willebrand Diseases

Considerable progress has been made in the past decade in describing the obstetrical and gynaecological aspects of von Willebrand's disease (VWD). In addition, epidemiological studies have established an approximately 11-16% prevalence of the laboratory diagnosis of VWD in women presenting with menorrhagia. However, it is not established presently whether an upfront VWD screening should be a part of the standard evaluation of menorrhagia. This is because it is presently not known whether therapy in the VWD patient tailored specifically for VWD will appreciably alter the natural history of menorrhagia compared with the non-VWD menorrhagia patient. There are also subtleties involved in securing the diagnosis of VWD in women presenting with menorrhagia in terms of fluctuation of von Willebrand factor (VWF) levels vis-à-vis the menstrual cycle and the potential impact of oral contraceptive on VWF levels. Regarding management of VWD-related menorrhagia, pending ongoing comparative trials of intranasal desmopressin (DDAVP), tranexamic acid, oral contraceptive and the levonorgestrel intrauterine device, specific recommendations cannot be made presently regarding the superiority of one intervention compared with the other. The management of VWD-related postpartum haemorrhage is also an area of active debate in terms of 'best practice' in type 1 (? prophylactic DDAVP), type 2 [? expectant management if factor VIII:C (FVIII:C) level normalizes] and type 3 patients (? intensity and duration of infusional therapy with a VWF-containing plasma-derived FVIII concentrate). This review summarizes the present state of knowledge and highlights numerous questions for future study based on our present understanding of VWD in women.

Topics: Deamino Arginine Vasopressin; Female; Hemostatics; Humans; Mass Screening; Menorrhagia; Postpartum Hemorrhage; von Willebrand Diseases

von Willebrand disease (vWD) is the commonest bleeding disorder in women. More than 70% of women with vWD suffer from menorrhagia and half of them suffer from dysmenorrhea. There is also the risk of hemorrhage with ovulation and mid-cycle pain. These have a significant effect on all aspects of quality of life. vWD also can be the underlying cause of menorrhagia in a small but significant proportion of women. There are still several unanswered issues in the diagnosis and management of menorrhagia in these women. There is no consensus whether testing for vWD should be part of the routine investigations in menorrhagia. Diagnosis of vWD is difficult. There are intraindividual variations in von Willebrand factor and factor VIII levels influenced by age, race, and blood group. This is further complicated in women because of the fluctuation of these factor levels during the menstrual cycle and possibly with hormonal therapy. The diagnosis of menorrhagia is also difficult due to the lack of a simple objective tool for the assessment of menstrual blood loss. In vWD, the treatment of menorrhagia is usually medical, but there is lack of prospective data on the efficacy of commonly used medical therapies in these women. The levonorgestrel intrauterine system, Mirena, is effective and should be considered prior to surgical management. Surgical interventions may be required in patients unresponsive to medical treatments. These procedures can be complicated by hemorrhage in these women. A multidisciplinary approach in the management of these women is essential in ensuring an optimal outcome. Multicenter clinical trials are required to answer the controversial issues in the management of women with vWD.

Topics: Adolescent; Adult; Antifibrinolytic Agents; Contraceptives, Oral, Synthetic; Deamino Arginine Vasopressin; Endometrium; Female; Genital Diseases, Female; Humans; Levonorgestrel; Menorrhagia; Middle Aged; Quality of Life; Tranexamic Acid; von Willebrand Diseases

Topics: Aminocaproates; Blood Component Transfusion; Deamino Arginine Vasopressin; Factor VIII; Female; Hemophilia A; Hemostasis; Humans; Isoantibodies; Menorrhagia; Phenotype; Plasma; Pregnancy; Pregnancy Complications, Hematologic; Tranexamic Acid; von Willebrand Diseases; von Willebrand Factor

Topics: Adult; Deamino Arginine Vasopressin; Diagnosis, Differential; Drug Monitoring; Female; Hemostatics; Humans; Medical History Taking; Menorrhagia; Nurse Practitioners; Nurse's Role; Patient Education as Topic; Physical Examination; Primary Health Care; von Willebrand Diseases

Accelerated clearance of von Willebrand factor (VWF) has been recently identified as a major pathophysiologic mechanism inducing low VWF in some patients with von Willebrand disease (VWD). The frequency of bleeding and the best treatment of these patients have never been evaluated prospectively in large series of patients. It was the aim of the present study to prospectively evaluate clinical events of 60 heterozygous patients with VWD Vicenza (VWD-VI) carrying R1205H VWF mutation and 23 with C1130F mutation, both characterised by markedly increased VWF clearance. During 71 months of follow-up, 65% of patients with VWD-VI and 61% with C1130F required treatment. The rate of spontaneous bleeding requiring consultation/treatment was 7.5/100 patients-year in patients with C1130F mutation vs. 1.9/100 patients-year in those with R1205H (p=0.004). This difference persisted also by multivariate analysis adjusted for sex, age and blood group (hazard ratio [HR]=3.3 for C1130F, 95% confidence interval [CI] 1.16-9.27) and females were at greater risk of bleeding (HR=3, 95%CI 1.01-9.93) because of menorrhagia. Only 3/15 (20 %) women in fertile age with VWD-VI compared to 8/9 (89 %) with C1130F mutation required consultation/treatment for menorrhagia (iron supplementation, combined oral contraceptives, tranexamic acid). Almost all dental extractions, minor surgeries and deliveries occurring during follow-up were successfully managed with desmopressin. Major surgery required factor VIII/VWF concentrates, but a few cases benefited from desmopressin. In conclusion, similar to patients with type 1 VWD, also in patients with increased VWF clearance desmopressin maintains a major therapeutic role.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Deamino Arginine Vasopressin; Female; Follow-Up Studies; Hemorrhage; Hemostatics; Humans; Infant; Italy; Male; Menorrhagia; Middle Aged; Mutation; Prospective Studies; Risk; Sex Factors; von Willebrand Disease, Type 1; von Willebrand Diseases; von Willebrand Factor

The optimal management of menorrhagia among women with abnormal laboratory haemostasis is uncertain. In a crossover study, 116 women with menorrhagia [pictorial blood assessment chart (PBAC) score >100], negative gynaecological evaluation and abnormal laboratory haemostasis were randomly assigned to either intranasal desmopressin (IN-DDAVP) or tranexamic acid (TA) therapy for two menstrual cycles. The subjects then crossed over to the second study drug for two additional cycles. Menstrual blood loss (MBL) was measured by PBAC scores at baseline and after each menstrual cycle. Quality of life (QOL) was assessed with four validated instruments. There was a statistically significant decrease in PBAC scores for both treatments. On average, the estimated decrease in the PBAC from baseline was -64.1 [95% confidence interval (CI) = -88.0, -40.3] for IN-DDAVP and -105.7 (95% CI = -130.5, -81.0) for TA. The decrease in PBAC score was greater for TA than IN-DDAVP (a difference of 41.6, P-value = 0.0002, 95% CI = 19.6, 63.6). The test for treatment-type effect was significant (P < 0.0001) suggesting a greater reduction in PBAC score with TA. Use of both IN-DDAVP and TA improved QOL by all four instruments. We conclude that both medications reduced MBL and improved QOL among females with menorrhagia and abnormal laboratory haemostasis, but TA proved more effective.

Topics: Administration, Intranasal; Administration, Oral; Adult; Antifibrinolytic Agents; Cross-Over Studies; Deamino Arginine Vasopressin; Female; Headache; Hemostatics; Humans; Menorrhagia; Prospective Studies; Quality of Life; Tranexamic Acid

Desmopressin, a synthetic analogue of the natural hormone vasopressin, stimulates endogenous haemostasis and exerts a powerful myometrial and vasoconstrictor action in a variety of pharmacological preparations. Both mechanisms of action may have therapeutic value for the treatment of intrauterine device (IUD)-related menorrhagia, which is believed to be caused not only by altered local haemostasis but also-according to a new hypothesis-by decreased vascular uterine resistance. The aim of this prospective study was to evaluate the effect of vasopressin drug on menstrual blood loss and on changes, if any, in uterine flow impedance. Mefenamic acid, which is commonly used to treat IUD-related menorrhagia, was administered as a comparison.. Twenty-four women with IUD-induced menorrhagia were recruited and randomly allocated to treatment with either desmopressin or mefenamic acid. Menstrual blood loss (measured by pictorial blood loss assessment chart) and uterine artery resistance (measured with transvaginal colour Doppler) performed in two pretreatment periods were compared with 3-month treatment periods.. Menstrual blood loss was significantly reduced in both treatment groups. In the desmopressin group, the effect was clinically useful in all subjects, but in the mefenamic group menstrual blood loss was consistently menorrhagic in two patients. No significant differences were observed in the uterine artery pulsatility index before and during treatment.. Desmopressin may be a useful therapeutic tool for many women with IUD-related menorrhagia. Its mechanism of action lies in an ability to enhance local haemostasis, without affecting uterine blood flow.

Topics: Adult; Cyclooxygenase Inhibitors; Deamino Arginine Vasopressin; Female; Hemostatics; Humans; Intrauterine Devices, Copper; Mefenamic Acid; Menorrhagia; Pilot Projects; Treatment Outcome

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.

Topics: Administration, Intranasal; Adolescent; Adult; Blood Coagulation Disorders, Inherited; Cross-Over Studies; Deamino Arginine Vasopressin; Double-Blind Method; Female; Hemostatics; Humans; Menorrhagia; Middle Aged; Treatment Outcome; von Willebrand Diseases

The objective of this study was to investigate the efficacy and safety of desmopressin (1-desamino-8-D-arginine vasopressin) compared with placebo in the reduction of menstrual blood loss in women with menorrhagia and prolonged bleeding time, but without common coagulation factor deficiencies. We performed a randomized, double-blind, cross-over study using 300 microg desmopressin nasal inhalation or placebo treatment in one of the two first treatment cycles. Desmopressin was given only for the 2 days during which the bleeding had been at a maximum in the previous baseline cycle. A third open cycle involved combined treatment with desmopressin and tranexamic acid during the 2 days for all patients. Menstrual blood loss during the treatment periods was compared with blood loss during placebo-treated periods using objective measurement. A significant reduction of menstrual blood loss was found in the cycles treated with combined desmopressin and tranexamic acid compared with placebo. When analyzing the blood loss during the two treatment days, there was a significant reduction in blood loss for the 2 days with desmopressin alone versus placebo. The treatment was well tolerated and no serious adverse events were recorded. In conclusion, we find that nasal desmopressin is a possible complement for the medical treatment of menorrhagia.

Topics: Adult; Bleeding Time; Cross-Over Studies; Deamino Arginine Vasopressin; Double-Blind Method; Female; Flushing; Headache; Hemorrhagic Disorders; Hemostatics; Humans; Menorrhagia; Nausea; Tranexamic Acid; Treatment Outcome

An open-label multicentre trial was conducted to evaluate high-dose DDAVP (desmopressin acetate) intranasal spray (Stimate; 1.5 mg mL(-1)), for the control of bleeding in 333 patients with mild haemophilia A, mild or moderate type 1 von Willebrand disease, or symptomatic carriers of haemophilia A. Overall, 278 patients received 2170 doses of high-dose DDAVP intranasal spray (1.5 mg mL(-1)). Using study-defined guidelines, patients evaluated the efficacy of high-dose DDAVP intranasal spray (1.5 mg mL(-1)) as 'excellent' or 'good' in 743 (95%) of 784 bleeding episodes. It demonstrated 'excellent' results in 384 (93%) of 413 administrations for prophylaxis and in eight of eight uses prior to acute surgical or dental procedures. When used for the treatment of menorrhagia, the efficacy of high-dose DDAVP intranasal spray (1.5 mg mL(-1)) was rated as 'excellent' after 655 (92%) of 721 daily uses. Of 2170 doses of high-dose DDAVP intranasal spray (1.5 mg mL(-1)), 172 (8%) were associated with adverse events. A total of 272 adverse events were reported among 80 patients. Of these, 239 (88%) were mild or moderate in intensity and only one patient was removed from the study due to an adverse event. These results demonstrate the safety and efficacy of high-dose DDAVP intranasal spray (1.5 mg mL(-1)) for control of bleeding episodes in patients with mildly decreased levels of factor VIII, von Willebrand factor, or both.

Topics: Administration, Intranasal; Adolescent; Adult; Blood Loss, Surgical; Child; Child, Preschool; Cohort Studies; Consumer Product Safety; Deamino Arginine Vasopressin; Female; Follow-Up Studies; Hemophilia A; Hemorrhage; Heterozygote; Humans; Male; Menorrhagia; Middle Aged; Therapeutic Equivalency; von Willebrand Diseases

We report our experience with the incidence of adverse events during the use of Stimate brand intranasal desmopressin acetate (IN DDAVP) for patients with haemophilia A (HA) or von Willebrand disease (vWD) after noting two severe adverse events in one adult patient. All patients with documented vWD (type 1 or 2 A) or haemophilia A (mild, moderate or symptomatic carrier) from the Emory Comprehensive Hemophilia Center who had IN DDAVP challenge testing or were using Stimate for treatment of bleeding were evaluated for adverse events by patient report or nursing observation of clinical signs and symptoms. Forty patients were studied. Sixty-eight per cent (27/40) experienced clinical signs and/or symptoms. The majority of these symptoms were mild, however several patients reported moderate to severe side-effects and one adult patient required medical intervention for symptomatic hyponatraemia. In our experience, two-thirds of patients tested experienced adverse signs and/or symptoms with the use of Stimate; considerably higher than that reported from preliminary results in the literature. Young age did not correlate positively with adverse reactions. Severe adverse events requiring medical intervention were rare, however symptoms such as moderate to severe headache, nausea, vomiting and weakness may necessitate evaluation for hyponatraemia. This is the first report of symptomatic hyponatraemia in an adult patient with recommended dosing of Stimate. Side-effects may be minimized if patients adhere to instructions regarding fluid intake and composition while using IN DDAVP.

Topics: Administration, Intranasal; Adolescent; Adult; Age Factors; Child; Child, Preschool; Deamino Arginine Vasopressin; Fatigue; Female; Headache; Hemophilia A; Hemostatics; Heterozygote; Humans; Hyponatremia; Male; Menorrhagia; Middle Aged; Nausea; Potassium; Sex Factors; Sodium; von Willebrand Diseases; Weight Gain

Approximately 50% of female carriers of hemophilia A have factor VIII (FVIII) levels below 0.5 IU/dL and may be categorized as having mild hemophilia. Females with hemophilia may go undiagnosed for years because the most common symptoms - menorrhagia and bleeding after childbirth - also occur in females without hemophilia. Females with hemophilia can exhibit increased bleeding tendencies despite current guidelines of expected, adequate FVIII levels. The cases described illustrate the clinical variability and presentation of hemophilia in females and highlight the importance of a timely diagnosis, effective management, and monitoring. Prophylactic factor replacement therapy is recommended in females with hemophilia, particularly those with joint disease or gynecologic complications. Affected individuals should receive infusion training and education on treatment options, physical activities, the importance of treatment adherence, and recognizing bleeding symptoms warranting treatment. Further study is needed to increase awareness of hemophilia in females and reassess current guidelines for their management and monitoring.

Topics: Adolescent; Aged; Chromosome Inversion; Deamino Arginine Vasopressin; Disease Management; Drug Substitution; Factor VIII; Female; Hemarthrosis; Hemophilia A; Heterozygote; Humans; Introns; Male; Menorrhagia; Middle Aged; Pedigree; Recombinant Proteins; Tranexamic Acid; Young Adult

Due to lack of patient/health care provider awareness causing delayed diagnosis, the bleeding phenotype and provider interventions in adolescents with heavy menstrual bleeding (HMB) and bleeding disorders (BD) may be different when compared to adults.. The aim of this study was to compare/characterize bleeding phenotype and provider interventions in postmenarchal adolescents < 18 years and premenopausal adults ≥ 18 years with HMB and BD.. Patient demographics, BD, and provider interventions/therapy details for HMB were compared between both age groups enrolled in the Centers for Disease Control and Prevention (CDC) Female Universal Data Collection (UDC) surveillance project in United States hemophilia treatment centres. Cross-sectional descriptive analyses including frequency distributions, summary statistics, bivariate and logistic regression analyses were performed.. Of 269 females (79 adolescents; median age 16 years, interquartile range (IQR) = 2; 190 adults; median age 27 years, IQR = 13) evaluated, BD distribution was similar in both groups. Compared to adolescents, adults more often had family history of bleeding (Adjusted odds ratios [AOR] = 2.6, 1.3-5.6), delay in diagnosis (AOR = 2.5, 1.2-4.9), bleeding with dental procedures (AOR = 2.0, 1.0-4.0), gastrointestinal bleeding (AOR = 4.6, 1.0-21.9), anaemia (AOR = 2.7, 1.4-5.2), utilized desmopressin less often (AOR = 0.4, 0.2-0.8) and underwent gynaecologic procedure/surgery more frequently (AOR = 5.9, 1.3-27.3).. Bleeding phenotypes of adolescents and adults with HMB and BD were different with more frequent bleeding complications, anaemia, gynaecologic procedures/surgeries, less desmopressin use and more delay in diagnosing BD in adults. Longitudinal studies are needed to determine whether improved patient/provider awareness and education will translate to early diagnosis and timely management of BD/HMB in adolescents that may prevent/reduce future haematologic/gynaecologic complications.

Topics: Adolescent; Adult; Anemia; Antifibrinolytic Agents; Blood Coagulation Disorders; Cross-Sectional Studies; Deamino Arginine Vasopressin; Delayed Diagnosis; Female; Gastrointestinal Hemorrhage; Hemostatics; Humans; Logistic Models; Menopause; Menorrhagia; Odds Ratio; Phenotype; Young Adult

Platelet function defects (PFD) are reported to occur frequently in adult women with heavy menstrual bleeding (HMB). Few studies on adolescent HMB report varying incidence rates (2-44%) for PFD. We reviewed our institutional experience in detecting and managing PFD in adolescent HMB. Postmenarchial girls and adolescents with HMB seen at our institution undergo a comprehensive bleeding disorder work-up by paediatric haematology and paediatric gynaecology providers. Whole blood platelet aggregometry (WBPA) is performed as a second tier test after excluding thrombocytopaenia, coagulation factor deficiencies and Von Willebrand disease (VWD). We retrospectively reviewed the medical records of adolescents with HMB seen between June 2009 and November 2010, as approved by the Institutional Review Board. Patient demographics, clinical features, laboratory results, therapy details and patient outcome information were analysed. Overall, 114 postmenarchial girls and adolescents with HMB were evaluated; 68 patients (59%) had WBPA study performed. Nineteen patients (28%) had at least one aggregation or secretion defect; 12 (18%) had two or more such defects. Treatment included hormonal therapy (13/19; 68%), antifibrinolytic agents (8/19; 42%) and intra-nasal DDAVP (3/19; 16%). Thirteen patients (81%) had improved outcome (median follow-up--15.6 months; range of 1-66 months). In this study, PFD were identified in nearly one-third of girls with HMB, with the majority of these having two or more defects as identified by WBPA. Further prospective studies are needed to better define the prevalence and address appropriate management of HMB and other bleeding complications of PFD in adolescents.

Topics: Adolescent; Adult; Antifibrinolytic Agents; Blood Platelets; Child; Deamino Arginine Vasopressin; Female; Humans; Menorrhagia; Platelet Aggregation; Platelet Function Tests; Retrospective Studies; Young Adult

Recent studies have suggested a unifying pathophysiological concept to explain the underlying defects of von Willebrand factor (VWF) causing von Willebrand disease (VWD) and have highlighted the relevance of simple VWF related activities in producing a useful diagnosis. A standardized bleeding history condensed into a final bleeding score and few widely available laboratory tests, such as VWF ristocetin cofactor activity, VWF antigen and factor VIII (FVIII), in the index case and in his/her relatives are of critical importance. Ristocetin-induced platelet aggregation (RIPA) should also be tested. Trial with desmopressin should be carried out in patients, except those with virtual absence of VWF or with increased RIPA. Desmopressin should be used in all responsive patients as first choice. Substitutive treatment with VWF/FVIII containing products should be used in unresponsive patients, in those with heightened response to desmopressin or in those undergoing interventions requiring good hemostasis for more than 3-5 days. Special consideration should be deserved to the treatment of menorrhagia and parturition.

Topics: Deamino Arginine Vasopressin; Factor VIII; Female; Hemorrhage; Hemostasis; Hemostatics; Humans; Male; Menorrhagia; Menstruation; Pregnancy; Pregnancy Complications, Hematologic; von Willebrand Diseases; von Willebrand Factor

In women, von Willebrand disease (VWD) is the most common inherited bleeding disorder. Since VWD and other inherited bleeding disorders are autosomal disorders, they affect women and men. Menorrhagia, or heavy menstrual bleeding (HMB), is the most common symptom of women with bleeding disorder experience. Objectively, it is defined as bleeding that lasts for more than seven days or results in the loss of more than 80 ml of blood per menstrual cycle. The prevalence of menorrhagia in a woman with a bleeding disorder ranges from 32 to 100% in patients with VWD, from 5 to 98% in patients with a platelet dysfunction and from 35 to 70% in women with a rare factor deficiency. A detailed history and a careful physical exam are the first steps towards a diagnosis in adolescents, adding a PBAC>100 increased the sensitivity of the screening tool further to 95%. Laboratory testing should be made at the time of menstrual bleeding in an effort to capture the lowest level of VWF:Ag and FVIII:C. Treatment options for menorrhagia in VWD: (1) antifibrinolytic therapy with tranexamic acid, (2) the non-transfusional agent desmopressin (DDAVP), (3) purified blood products that contain factor VIII and VWF concentrated from plasma and (4) hormonal preparations.

Topics: Adolescent; Antifibrinolytic Agents; Deamino Arginine Vasopressin; Female; Hemostatics; Humans; Menorrhagia; von Willebrand Diseases

Recent studies indicate that bleeding disorders, particularly von Willebrand disease (VWD) is more prevalent than previously thought in adolescents with menorrhagia. Menorrhagia management in undiagnosed disorders of hemostasis may be associated with unwanted risks and complications. The prevalence of symptomatic VWD in the pediatric primary care setting appears to be 0.11% (95% CI, 0.04-0.25%). Studies evaluating the prevalence of VWD in adolescents with menorrhagia have included over 500 patients with a prevalence range from 3 to 36% depending on the clinical setting studied, with the highest prevalence seen in adolescents referred to an outpatient Hemophilia Center, while the lowest prevalence is seen in the acute hospital setting. Recently, the diagnosis of VWD has been facilitated by the use of pediatric bleeding questionnaires that have proved useful in quantifying the severity of bleeding symptoms. Treatment of VWD is often complex because a combination of therapies is often required. Potential treatment options include estrogen-progesterone preparations, desmopressin, antifibrinolytic agents and von Willebrand factor concentrates. More research is needed to evaluate the effectiveness of the various treatment modalities in the adolescent population.

Topics: Adolescent; Aminocaproic Acid; Antifibrinolytic Agents; Child; Contusions; Deamino Arginine Vasopressin; Epistaxis; Female; Hemostatics; Humans; Medical History Taking; Menorrhagia; Platelet Transfusion; Prevalence; Surveys and Questionnaires; Tranexamic Acid; von Willebrand Diseases; von Willebrand Factor

Reproductive tract bleeding in women is a naturally occurring event during menstruation and childbirth. In women with menorrhagia, however, congenital bleeding disorders historically have been underdiagnosed. This consensus is intended to allow physicians to better recognize bleeding disorders as a cause of menorrhagia and consequently offer effective disease-specific therapies.

Topics: Adult; Blood Coagulation Disorders; Deamino Arginine Vasopressin; Decision Trees; Factor VIII; Female; Hemostatics; Humans; Menorrhagia; Postpartum Hemorrhage; Pregnancy; Pregnancy Complications, Hematologic; Quality of Life; von Willebrand Diseases; von Willebrand Factor

Intranasal desmopressin (IN-DDAVP) is used for home treatment of menorrhagia in women with inherited bleeding disorders. The effect of IN-DDAVP on laboratory haemostatic parameters in women with menorrhagia related to platelet dysfunction is unknown. We evaluated the effects of IN-DDAVP on haemostatic parameters in women with menorrhagia and platelet dysfunction and correlated them with menstrual flow. Eleven women (aged 18-45) with menorrhagia and haemostatic abnormalities had determination of von Willebrand factor antigen (VWF:Ag), von Willebrand factor ristocetin cofactor (VWF:RCo) activity, factor VIII coagulant activity (FVIII:C), platelet aggregation and platelet adenosine tri-phosphate (ATP) release pre-IN-DDAVP and 60-min post-IN-DDAVP. Eight of eleven women underwent platelet function analyzer (PFA-100) closure time determination with collagen/adrenaline and collagen/adenosine diphosphate cartridges pretreatment and post-treatment. IN-DDAVP was administered during two consecutive menstrual cycles. Menstrual flow was assessed during each cycle using a pictorial blood assessment chart. Treatment with IN-DDAVP resulted in elevated VWF levels and shortened PFA-100 closure time with significant inverse correlation between shortening of PFA-100 closure times and increases in VWF levels. There were also significant inverse correlations between changes in menstrual flow and changes in VWF:Ag (P = 0.02), VWF:RCo (P = 0.04) and FVIII:C (P = 0.006), following treatment. In vitro platelet aggregation and platelet ATP release response did not correct and did not correlate with changes in menstrual flow. Our results demonstrate a correlation between haemostatic parameters and menstrual flow following IN-DDAVP in women with menorrhagia and platelet dysfunction.

Topics: Adenosine Triphosphate; Administration, Intranasal; Adolescent; Adult; Bleeding Time; Blood Platelet Disorders; Deamino Arginine Vasopressin; Factor VIII; Female; Hemostatics; Humans; Menorrhagia; Middle Aged; Platelet Aggregation; Severity of Illness Index; von Willebrand Factor

Topics: Adult; Deamino Arginine Vasopressin; Female; Hemostatics; Humans; Menorrhagia; von Willebrand Diseases

Topics: Adolescent; Antifibrinolytic Agents; Bernard-Soulier Syndrome; Comorbidity; Deamino Arginine Vasopressin; Epistaxis; Female; Hemostatics; Humans; Menorrhagia; Recurrence; Thrombasthenia; Tranexamic Acid

The purpose of this study was to examine patterns of use for oral contraceptive and desmopressin acetate nasal spray, both used in managing menorrhagia in adolescents with von Willebrand disease (vWD). Hospital records of adolescents with documented vWD and menorrhagia were reviewed retrospectively. Subjects with vWD type 1 (n = 36) administered either oral contraceptives (OC) or intranasal desmopressin acetate (DDAVP) and followed from 6 months to 4 years were selected for inclusion. Treatment outcomes were examined with respect to effectiveness and safety. Assessing menstrual blood loss using PBAC scores from pretreatment and treatment periods determined effectiveness. Safety was evaluated by monitoring reported adverse events. No significant differences were identified in treatment effectiveness for controlling menorrhagia in vWD adolescents in the OC and intranasal DDAVP group comparisons: 86% versus 77% (P > 0.05), respectively. When combining both treatment groups, the majority of vWD adolescents, 81% (P > 0.05), experienced alleviation of menorrhagia symptoms. Treatment failures were attributed to either the inability of a regimen to control bleeding or to adverse events, including severe headaches and flushing with DDAVP. Safety outcomes were not significantly greater in vWD patients with menorrhagia when OC were compared with intranasal DDAVP. Both medical approaches, OC and DDAVP nasal spray, used in managing menorrhagia in adolescents with documented type I vWD were well tolerated and showed equivalent effectiveness, and no serious adverse events were reported.

Topics: Administration, Intranasal; Adolescent; Child; Contraceptives, Oral; Deamino Arginine Vasopressin; Female; Hematocrit; Hemostatics; Humans; Menorrhagia; Retrospective Studies; Treatment Outcome; von Willebrand Diseases

The primary objective of this study was to investigate the correlation between fibrinolytic activity in menstrual fluid and total menstrual blood loss during menstruation. We also wanted to evaluate the influence of desmopressin nasal inhalation on the local fibrinolytic activity in menstrual fluid. Six women with objectively verified menorrhagia and six women with normal menstrual blood loss were examined. With a slender catheter introduced through the cervical canal, menstrual fluid was collected on the day in the cycle when the most intense bleeding occurred. The fibrinolytic activity in menstrual fluid was measured both as plasmin content using an amidolytic method with chromogenic substrate and with a fibrin plate method. A significant correlation between the amount of menstrual blood loss and fibrinolytic activity was found in menstrual fluid of both groups and with both methods. We could not find an increased fibrinolytic activity in menstrual fluid when the women with menorrhagia were treated with desmopressin nasal inhalation. Knowledge of the local factors influencing monthly blood loss can be valuable when searching for more effective medical treatment of menorrhagia. Apprehension that desmopressin should increase local fibrinolytic activity in menstrual fluid could not be confirmed.

Topics: Administration, Inhalation; Blood Coagulation Tests; Case-Control Studies; Deamino Arginine Vasopressin; Female; Fibrinolysin; Fibrinolysis; Hemorrhage; Humans; Menorrhagia; Menstruation

Topics: Animals; Animals, Genetically Modified; Autoantibodies; Deamino Arginine Vasopressin; Factor IX; Factor VIII; Female; Genetic Therapy; Hemophilia A; Hemostatics; Humans; Male; Menorrhagia; Mutation; Recombinant Proteins; Sex Factors; Swine; Synovitis; von Willebrand Diseases

Two women aged 39 and 30 years were investigated for possible coagulation disorders because of menorrhagia, anaemia and postoperative haemorrhages. These investigations revealed that they had type 1 Von Willebrand's disease. During the treatment with desmopressin, factor VIII and Von Willebrand factor (VWF) activity normalised. About one third of the patients referred to a gynaecologist for menorrhagia have an inherited bleeding disorder, of which type 1 Von Willebrand's disease is the most prevalent. Once a gynaecological cause of the menorrhagia has been excluded, or in the case of an increased risk on the basis of the medical history, a limited haemostatic investigation can establish or exclude an inherited coagulation disorder. For women with a coagulation disorder the menorrhagia can be treated. Surgical interventions can be carried out safely following treatment with desmopressin or factor VIII/VWF concentrates.

Topics: Adult; Anemia; Deamino Arginine Vasopressin; Factor VIII; Female; Hemostatics; Humans; Menorrhagia; Postoperative Hemorrhage; von Willebrand Diseases; von Willebrand Factor

An international registry was established on the reproductive health of women with types of von Willebrand disease (vWd) unresponsive to DDAVP. Data was collected on 44 women from 16 treatment centers in nine countries. Severe menorrhagia requiring blood product therapy occurred at least once in 80% of the women for whom data was reported. Most of the reported episodes occurred prior to the diagnosis of vWd and/or the use of oral contraceptive (OC) therapy. OC therapy was clinically effective in the treatment of chronic menorrhagia in 22 of 25 (88%) women treated. Two of the women, however, were unable to tolerate chronic OC use and a third became refractory to treatment. Hysterectomy was performed in 10 of the 44 women (23%). The reported indication for six of the procedures was menorrhagia. Seventy percent were performed at two treatment centers, suggesting different thresholds for the performance of the procedure. There were 69 pregnancies reported in 31 of the 44 women. Fifteen of the pregnancies resulted in spontaneous abortions. The incidence of miscarriage was 22% and appeared clustered, with 10 of 15 of the miscarriages occurring in just four of the women.

Topics: Abortion, Spontaneous; Adult; Blood Coagulation Factors; Blood Transfusion; Contraceptives, Oral, Hormonal; Deamino Arginine Vasopressin; Europe; Female; Humans; Hysterectomy; Menorrhagia; Postpartum Hemorrhage; Pregnancy; Pregnancy Outcome; Registries; Treatment Failure; United States; von Willebrand Diseases

Topics: Adolescent; Child; Deamino Arginine Vasopressin; Epistaxis; Female; Humans; Male; Menorrhagia; Thrombocytopenia