Safety and Effectiveness of Desmopressin for the Management of Delivery and Major Surgery in Patients with Mild-Moderate Von Willebrand Disease: Final Analysis of the Prodeswil Study

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 759-759
Author(s):  
Augusto Bramante Federici ◽  
Giancarlo Castaman ◽  
Alfonso Iorio ◽  
Emily Oliovecchio ◽  
Prodeswil Investigators
Keyword(s):  
Side Effects ◽  
Clinical Efficacy ◽  
Oral Surgery ◽  
Biological Response ◽  
Von Willebrand Disease ◽  
Major Surgery ◽  
Efficacy And Safety ◽  
Inclusion Criteria ◽  
Bleeding Episodes ◽  
Von Willebrand

Abstract Introduction. Despite the fact that desmopressin (DDAVP) is considered the treatment of choice in the majority of patients with inherited von Willebrand disease (VWD), there are still open questions about the efficacy and safety of the use of DDAVP to manage recurrent bleeding episodes, delivery and major surgery. In fact, to avoid tachyphylaxis and possible side effects with repeated DDAVP injections, VWF concentrates are usually preferred to manage delivery and major surgery also in VWD patients proven to be DDAVP-responsive. No prospective data have been reported so far to correlate biological response with DDAVP clinical efficacy in VWD and guide clinical practice. Design, aims and methods. ProDesWilis an investigator-driven Pro spective study on D esmopressin e fficacy and s afety of patients with inherited von Wil lebrand disease assessed at enrolment for DDAVP biological response during a test-infusion. Inclusion criteria: VWD diagnosis without any age restriction according to bleeding score >4, VWF activity levels <45U/dL, and at least another affected member in the family. DDAVP Biological Response: VWD were classified as complete, partial or no-responders as previously reported (Blood 2008;111:3531). Treatment regimens: DDAVP given intravenously or subcutaneously (0.3 ug/Kg) or by nasal spray (4 ug/Kg) according to preparations available in different countries with or without standard doses of anti-fibrinolytic agents (Epsilon-amino-caproic acid, EACA or tranexamic acid, TA). In case of major surgery, DDAVP was used together with TA using a 3dayOn-4dayOff-3dayOn schedule. DDAVP efficacy-safety evaluated with criteria currently used for VWF concentrates, with poor efficacy defined when VWF concentrates were needed. Patients were prospectively followed up for 24 months by ProDesWil Investigators who reported detailed information about DDAVP therapy used for bleeds, deliveries, oral and minor/major surgeries Results. 268 patients were enrolled in this 24-month prospective study. DDAVP-biological response: 225/268 (85%) patients met inclusion criteria as VWD1(n=184), VWD1C (n=14), VWD2A(n=15), VWD2M(n=12). The 14 VWD1C with accelerated clearance carried C1130F and R1205H mutations. DDAVP biological response was complete, partial and absent in 89%, 10% and 1% of all VWD. DDAVP clinical efficacy and safety: during the 24-month follow-up 84/225 (37.3%) received DDAVP for bleeding episodes (n=104), oral surgeries (n=33), deliveries (n=12), other minor/major surgeries (n=25). Total DDAVP injections were 652 with median, range/episode during bleeds (2,1-12), oral surgeries (1,1-10), deliveries (3,1-13), minor/major surgeries (3.6,1-16). Clinical efficacy was excellent/good in bleeds (93.3%), oral surgery (100%), deliveries (91.7%), minor/major surgeries (92.3%). All VWD treated for oral surgery with (75%) and without (25%) EACA/TA had excelled/good outcomes. Efficacy was rated excellent/good in 96/104 bleeds, with 8 episodes rated poor during menorrhagia (n=4) in 2 VWD1 and 2 VWD2A, during nose (n=2) and gastrointestinal (n=2) bleeds in 3 VWD2A and 1 VWD1C. 11/12 deliveries had excellent/good outcome with poor response in only one VWD1C who required VWF concentrates after caesarean section. All the 11/25 cases with minor surgeries had excellent outcomes. Among the 14/25 major surgeries [abdominal (n=5), hysterectomy (n=3), tonsillectomy (n=3), orthopaedic and others (n=3)] 2 episodes (partial resection of kidney in VWD2A and tonsillectomy in VWD1) were rated poor. Side effects (16 cases) were mainly minor (flushing, headache, tachycardia) with water retention reported only in 2 patients who received >12 doses of DDAVP for delivery or major surgery. Conclusions: DDAVP is an effective, safe and cheap treatment for managing patients with mild-moderate VWD who showed complete biological response to this drug. Therefore, DDAVP must be always recommended as first line therapy in responsive VWD not only in bleeds and oral surgery but also in deliveries and major surgeries. On the other hands, DDAVP should be used with caution in VWD2A and VWD1 with partial response. The additional use of EACA/TA should be considered especially when DDAVP is required for more than 4 days. Disclosures No relevant conflicts of interest to declare.

Clinical Efficacy and Safety Versus Biological Response of Desmopressin (DDAVP) In Inherited Von Willebrand Disease (VWD) Types 1 and 2: Initial Results From the International Study Group on DDAVP In VWD In a Cohort of 229 Patients

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 238-238
Author(s):  
Augusto B. Federici ◽  
Alfonso Iorio ◽  
Giancarlo Castaman
Keyword(s):  
Clinical Efficacy ◽  
Demographic Data ◽  
Biological Response ◽  
Working Party ◽  
Von Willebrand Disease ◽  
Efficacy And Safety ◽  
Inclusion Criteria ◽  
Excessive Bleeding ◽  
Baseline Levels ◽  
Von Willebrand

Abstract Abstract 238 Background: Desmopressin (DDAVP) is the treatment of choice for most patients with mild-moderate forms of von Willebrand Disease (VWD) because it can induce the release of von Willebrand Factor (VWF) from cellular compartments. However, despite the widespread use of DDAVP since 1977, there are only a few prospective clinical trials aimed at determining benefits and limits of this approach. Aims and design of the study: To correlate efficacy and safety with biological response of DDAVP in a large cohort of VWD1 and VWD2 patients followed-up for 24 months in a prospective observational study organized on behalf of the Working Party on DDAVP in VWD of the ISTH-SSC on VWF and of Italian Association of Hemophilia Centers (AICE). The study is registered at the EMEA with number EudraCT-2005-004496-38. Patients and Methods: VWD patients were enrolled after obtaining Ethical approval from local IRB. Inclusion criteria: inherited VWD without any age restriction, with previous diagnosis of VWD1 and VWD2 according to ISTH recommendations. Biological response: At enrollment patients were exposed to 0.3 ug/kg DDAVP intravenous injection and to blood withdrawal for measuring VWF/FVIII activities before and after 0.5, 1, 2 and 4 hours. Complete: both VWF:RCo and FVIII:C >50 IU/dL at 2 hours; partial: VWF:RCo or FVIII:C <50 IU/dL but increased at least 3-fold; absent: neither criterion. Clinical Response. Excellent: no excessive bleeding; Good: excess bleeding without need for VWF concentrate; Poor: excess bleeding with need for VWF concentrate. Statistical analyses were performed only on confirmed patients after the blind and independent evaluation by 2 members of the Steering Committee on these criteria: VWD=baseline levels of VWF:RCo <55 U/dL; VWD2= baseline VWF:RCo/Ag ratio≤ 0.6; VWD1 accelerated clearance: rapid increase of VWF:RCo/FVIII after 0.5–1 hrs with return to baseline levels after 2–4 hrs. Results: 229/268 (85%) patients enrolled at 13 participating Centers in Argentina, Brazil, Canada, Germany, Italy and Hungary were found to meet the inclusion criteria. Demographic data and lab tests (mean+SD) at baseline were as follows: Among VWD2, VWD2A(n=15), VWD2B(n=1), VWD2M(n=12), VWD2N(n=3) were identified. Biological response was complete, partial and absent in 89%, 10% and 1% of VWD and correlated with baseline levels of VWF:RCo<30 U/dL (Fisher's exact =0.001). Among VWD1, those (n=15) with C1130F and R1205H mutations showed accelerated clearance. During the 24-month follow-up, 62/86 (72%) patients received >1 injection of DDAVP for bleedings (n=102), deliveries (n=13), dental extractions (n=27), minor/major surgeries (n=46). Total number of injections was 652 with median, range/episode during bleedings (2,1-12), deliveries (3,1-3), dental extractions (1,1-6), surgeries (3.6,1-11). Clinical efficacy was excellent/good in bleedings (92%), deliveries (85%), dental extractions (100%), surgeries (91%). Poor efficacy was observed in 6 cases with VWD2A (n=4) during GI bleedings (n=3) or abdominal surgery (n=1) and VWD1 (n=2) during deliveries and surgery. Side effects observed in 16 patients were mainly minor, such as headache, facial flushing and tachycardia; water retention was reported in 2 cases (1 delivery, 1 surgery) only after >6 injections of the drug. Conclusions: Based on the results of this prospective clinical trial, we confirm that DDAVP is an effective and safe drug at low costs for managing patients with VWD1 and VWD2 once tested for their biological response: therefore it should be always considered as the first approach during bleedings and major/minor surgeries in responsive VWD patients. Disclosures: Federici: CSL Behring: Honoraria, Research Funding.

Efficacy and Safety of High-Intermediate-Purity VWF/FVIII Concentrates Given Repeatedly to Severe Patients with Von Willebrand Disease: An Italian Cohort Study on 32 Intensively Treated Cases.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4060-4060
Author(s):  
Augusto B. Federici ◽  
Belinda J. Cedron ◽  
Barbara Scimeca ◽  
Maria T. Canciani ◽  
Pier M. Mannucci
Keyword(s):  
Cohort Study ◽  
Side Effects ◽  
Von Willebrand Disease ◽  
Severe Bleeding ◽  
Efficacy And Safety ◽  
Inclusion Criteria ◽  
Mean Values ◽  
On Demand ◽  
Post Infusion

Abstract Background and Objectives. Patients with severe forms of von Willebrand’s disease (VWD) may have frequent episodes of mucocutaneous bleeding and also of hemarthrosis or hematomas. They are usually unresponsive to desmopressin (DDAVP) and must be treated with high- or intermediate-purity VWF/FVIII concentrates (VWFc). Due to the different VWF/FVIII composition of the VWFc, timing and dosage of infusions are still not completely standardized. Aim of this study was to evaluate the efficacy and safety of repeated infusions of VWFc given on demand, for bleeds and surgery, and on secondary long-term prophylaxis to our cohort of severe VWD patients. Design and Methods. This is a cohort study on 473 VWD patients regularly followed up at our Center for more than two years. Inclusion criteria: patients proven to be unresponsive to DDAVP and treated with VWFc with &gt; 25 exposure days (ED)/year (&gt; 50,000 FVIII U/year) during the previous 2 years. All patients were characterized by a bleeding severity score derived from a detailed history of 11 symptoms. Since VWFc available in Italy are still labeled in FVIII IU, patients were given 60 or 40 FVIII IU/Kg of high- (Alphanate, Fanhdi) or intermediate-purity (Haemate-P) in case of on demand or long term prophylaxis, respectively. Efficacy of VWFc used on demand versus prophylaxis (every other day or twice a week) regimens was based on resolution/reduction of bleeds and rated as excellent/good versus partial/poor clinical responses. Safety was measured by monitoring side effects and pre-post infusion FVIII levels during the first two weeks of treatment. Results. 32/473 (7%) patients only met the inclusion criteria. They were severe (bleeding scores &gt;15; VWF:RCo baseline levels &lt;10 U/dL), with confirmed VWD diagnosis (case n) of types 3 (7), 2A (8), 2B (6), 2M (5) and 1 (6). High (n= 9) and intermediate (n=12) VWFc were used on demand therapy in 21 VWD cases. Prophylaxis was started because of recurrent GI bleeds in 7 patients with VWD types 3 (n=1), 2A (n=4), 2M (n=1) and 1 (n=1) and for joint bleeds only in VWD type 3 (n= 4). Total amounts of FVIII:C Units (mean values with ranges ×1000 U/year) transfused were: on demand = 66.4 (51–123); secondary prophylaxis = 297 (117–720). Clinical response was excellent/good in &gt;95%, &gt;85%, &gt;90% surgeries, bleeds, prophylaxis, respectively. Prophylaxis could stop bleeding in 8 patients and largely reduced hospitalization for PRBC transfusions in the remaining 3. As far as safety, FVIII levels were always &lt;180 U/dL during bleeds and prophylaxis and &lt;210 U/dL during surgeries in all intensively treated VWD. No side effects, including thrombosis, were observed Interpretations and Conclusions. High- and intermediate-purity VWFc are effective and safe in severe forms of VWD also in patients exposed to intensive regimens of therapy, on demand or on prophylaxis. The use of pre-post infusion levels of FVIII is very useful to prevent unnecessary treatment with VWFc. Cost-effectiveness of prophylaxis regimens versus on demand therapy should be further investigated in large prospective studies.

Efficacy, Safety and Tolerability of a Novel High-Purity, Double Virus-Inactivated VWF/FVIII-Concentrate in the Treatment of Von Willebrand Disease (VWD) - Clinical Experience in the Treatment of Bleeding and Surgery.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2144-2144
Author(s):  
B.A. Schwartz ◽  
J. Windyga ◽  
M. von Depka ◽  
O. Walter ◽  
M. Jansen ◽  
...  
Keyword(s):  
Clinical Efficacy ◽  
Surgical Procedures ◽  
Von Willebrand Disease ◽  
Efficacy And Safety ◽  
Open Label ◽  
Prophylactic Regimen ◽  
Acute Bleeding ◽  
Good Efficacy ◽  
Bleeding Episodes ◽  
Type 3

Abstract Introduction: Wilate is a highly purified, double viral inactivated, VWF/FVIII-concentrate developed for the treatment of VWD. A program of prospective studies was conducted in VWD patients to investigate the clinical efficacy and safety of Wilate® in acute bleeding episodes, prophylaxis and surgical procedures. Methods: In these prospective open label studies 70 VWD patients (37 VWD of type 3) were treated with the VWF/FVIII concentrate Wilate and followed to assess clinical efficacy and tolerability. Dosing and monitoring were performed using FVIII assays. This is standard practice in most of the study sites and was feasible because of the product’s physiological 1:1 ratio and parallel PK profiles of FVIII and VWF. Dosing decisions were based on established guidelines and the investigators’ clinical judgment. The efficacy of the product was rated on a four-point scale by the investigator. Results: Bleeding- 43 patients (25 of type 3) were treated for a total number of 1088 bleeding episodes (BE). The median dose per exposure day (ED) was calculated to be 31 IU VWF/FVIII:C/kg and were treated for a median of 1.2 days, with excellent or good efficacy achieved in 96% of treatments. Surgery- Efficacy and safety was also studied in 31 VWD patients who underwent 54 elective or urgent surgical procedures of which 27 were classified as major; the overall efficacy was rated as excellent or good in most cases (94%), with a mean dose per infusion being 34 IU VWF/FVIII:C/kg. Pediatric Use- A total of 8 children below 12 years of age with 310 BE s were treated, with an excellent/good efficacy in 98% of bleedings. Prophylaxis- 19 patients were on a prophylactic regimen for more than 10 consecutive weeks (total of 2,338 ED), with an overall reduction of bleeding frequency. Tolerability - Out of 5,662 rated infusions in all studies, the tolerability was assessed as “very good” or “good” in 99% of the cases. Conclusions: The results of the prospective clinical trial program demonstrate the safety, efficacy and tolerability of this VWF/FVIII concentrate for the treatment of acute bleeding episodes, prophylaxis and surgical procedures in patients with VWD.

Clinical Efficacy and Safety of Wilate®, A New Generation, High-Purity VWF/FVIII-Concentrate with Optimized Pharmacokinetic Properties in the Treatment of Von Willebrand Disease.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1795-1795
Author(s):  
Jerzy Windyga ◽  
Antoaneta Zarkova ◽  
Olaf Walter ◽  
Guenter Auerswald
Keyword(s):  
Clinical Efficacy ◽  
Surgical Procedures ◽  
High Purity ◽  
Clinical Judgment ◽  
Von Willebrand Disease ◽  
Average Dose ◽  
Efficacy And Safety ◽  
New Generation ◽  
Type 3 ◽  
Von Willebrand

Abstract Purpose: Wilate® represents a new generation VWF/FVIII-concentrate for the treatment of von Willebrand patients with high purity and two independent virus inactivation steps. The high purity of the product was developed to preserve the functionality of Wilate®’s VWF/FVIII complex at a physiological ratio of about 1:1. Methods: A prospective multicenter study is conducted in 47 VWD patients to investigate the pharmacokinetics (PK) and clinical efficacy and safety of Wilate® in acute bleedings and surgical prophylaxis. For PK studies, plasma levels of VWF:RCo, FVIII:C, VWF:Ag were measured up to 72 hrs after injection of 50 IU of FVIII/kgBW. Clinical efficacy and tolerability was rated on a four-point scale. Final decisions on dosing were based on the investigators’ clinical judgment. Summary of results: Mean half-life of VWF:RCo in type 3 patients (n=9) was 17.1 hrs. Mean recovery for VWF:RCo was 1.5 [% per IU/kg] and 2.0 [% per IU/kg] for FVIII:C. The clearance for VWF:RCo was 2.5 [ml/h/kg] for all and 3.9 [ml/h/kg] in type 3 patients. 33 patients have been treated for a total number of 658 bleeds. Of these, 31 patients (69%) were type 3 patients. The average dose/kgBW/ED was calculated to 29.3 IU FVIII:C. Furthermore efficacy and safety was studied in 16 patients undergoing 24 surgical procedures. The overall efficacy (achievement of haemostasis) of Wilate® was rated as excellent or good for 23/24 procedures (96%). One patient with a laparoscopic cholecystectomy required two additional blood transfusions. The tolerability was assessed as very good/good by investigators and patients in all surgical cases. Conclusion: Wilate® documented favourable PK-properties in VWD patients. The interim results of these prospective clinical studies demonstrate the safety and efficacy of the double-virus-inactivated Wilate® for the treatment of acute bleeding episodes and surgical procedures in patients with VWD.

Prospective Multicenter Study on Subcutaneous Concentrated Desmopressin for Home Treatment of Patients with von Willebrand Disease and Mild or Moderate Hemophilia A

1996 ◽  
Vol 76 (05) ◽  
pp. 692-696 ◽  
Author(s):  
Francesco Rodeghiero ◽  
Giancarlo Castaman ◽  
Pier Mannuccio Mannucci
Keyword(s):  
Clinical Efficacy ◽  
Hemophilia A ◽  
Case Reports ◽  
Von Willebrand Disease ◽  
Hospital Treatment ◽  
Home Therapy ◽  
Self Administration ◽  
Bleeding Episodes ◽  
A Prospective Study ◽  
Von Willebrand

SummaryDesmopressin is the treatment of choice in most patients with von Willebrand disease (vWD) and mild hemophilia A (HA). Several studies have demonstrated that the intravenous and subcutaneous route of administration are equivalent in terms of pharmacokinetics and clinical efficacy. Home therapy of vWD and mild HA is desirable but so far there have been only a few case reports and no prospective studies. We report the results of a prospective study of home therapy in patients with vWD and mild-moderate HA using concentrated desmopressin self-administered subcutaneously. Clinical efficacy and safety were assessed by the patient using a questionnaire and direct interview. The patients were instructed on self-administration and dosage, reasons for treatment, recognition of side effects and recording clinical efficacy. The study lasted 12 months (range 6-17). During this time, 43/100 (43%) of the enrolled vWD patients (median basal VIII: C 24%, range 9-49) and 36/69 (52%) of HA patients (median basal VIII: C 10%, range 5-34) self-administered the drug. A total of 127 bleeding episodes requiring treatment occurred in patients with vWD and 92 in HA patients. There were 10 treatment failures of which 7 required in-hospital treatment. Overall, in 94% of treatments (excluding menorrhagia) the response was scored as excellent or good. In 86% of treated episodes of menorrhagia the response was scored as excellent or good. According to the patients, 81% of clinical situations would have required in-hospital treatment. Mild flushing, with or without headache, was the only consistent side-effect, reported in about 30% of treatments. In conclusion, home therapy with subcutaneous desmopressin for von Willebrand disease and hemophilia A was well accepted by the patients and proved feasible, efficacious and safe for the prevention or prompt treatment of bleeding.

scholarly journals Comparison of clinical efficacy and safety between dexmedetomidine and propofol among patients undergoing gastrointestinal endoscopy: a meta-analysis

2021 ◽  
Vol 49 (7) ◽  
pp. 030006052110327
Author(s):  
Weihua Liu ◽  
Wenli Yu ◽  
Hongli Yu ◽  
Mingwei Sheng
Keyword(s):  
Clinical Efficacy ◽  
Lower Risk ◽  
Gastrointestinal Endoscopy ◽  
Weighted Mean Difference ◽  
Meta Analysis ◽  
Similar Efficacy ◽  
Cochrane Library ◽  
Efficacy And Safety ◽  
Inclusion Criteria ◽  
Weighted Mean

Objective To compare the clinical efficacy and safety of dexmedetomidine and propofol in patients who underwent gastrointestinal endoscopy. Methods Relevant studies comparing dexmedetomidine and propofol among patients who underwent gastrointestinal endoscopy were retrieved from databases such as PubMed, Embase, and Cochrane Library. Results Seven relevant studies (dexmedetomidine group, n = 238; propofol group, n = 239) met the inclusion criteria. There were no significant differences in the induction time (weighted mean difference [WMD] = 3.46, 95% confidence interval [CI] = −0.95–7.88, I2 = 99%) and recovery time (WMD = 2.74, 95% CI = −2.72–8.19, I2 = 98%). Subgroup analysis revealed no significant differences in the risks of hypotension (risk ratio [RR] = 0.56, 95% CI = 0.25–1.22) and nausea and vomiting (RR = 1.00, 95% CI = 0.46–2.22) between the drugs, whereas dexmedetomidine carried a lower risk of hypoxia (RR = 0.26, 95% CI = 0.11–0.63) and higher risk of bradycardia (RR = 3.01, 95% CI = 1.38–6.54). Conclusions Dexmedetomidine had similar efficacy and safety profiles as propofol in patients undergoing gastrointestinal endoscopy.

scholarly journals Efficacy and safety of a VWF/FVIII concentrate (wilate®) in inherited von Willebrand disease patients undergoing surgical procedures

Haemophilia ◽  
2016 ◽  
Vol 23 (2) ◽  
pp. 264-272 ◽  
Author(s):  
A. Srivastava ◽  
M. Serban ◽  
S. Werner ◽  
B. A. Schwartz ◽  
C. M. Kessler ◽  
...  
Keyword(s):  
Surgical Procedures ◽  
Von Willebrand Disease ◽  
Efficacy And Safety ◽  
Von Willebrand

Clinical assessment of efficacy and safety of DDAVP

2010 ◽  
Vol 30 (S 01) ◽  
pp. S172-S175 ◽  
Author(s):  
W. Miesbach ◽  
S. Krekeler ◽  
O. Dück ◽  
B. Llugaliu ◽  
G. Asmelash ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Adverse Reactions ◽  
Fluid Intake ◽  
Von Willebrand Disease ◽  
Haemophilia A ◽  
Efficacy And Safety ◽  
Drug Reactions ◽  
Clinical Routine ◽  
Von Willebrand ◽  
Mild Haemophilia

SummaryThe efficacy of DDAVP (1-deamino-8-D-argi-nine-vasopressin, desmopressin) in mild haemophilia A and von Willebrand disease (VWD) has been established and the use of this well tolerated drug has become clinical routine. In case of increased fluid intake and based on very rarely occurring hyponatraemia, the indication of administration of DDAVP intravenously (i. v.) has to be performed diligently in elderly patients and in children below the age of five years. Aim, patients: Due to clinical practice we were interested in finding prospective parameter potentially correlating with adverse reactions of DDAVP and initiated this study. From 2007 to 2008, we included 49 patients suspicious to suffer from mild haemophilia A (n = 1) or VWD (n = 48) and investigated efficacy and safety of DDAVP after intravenous administration (mean: 0.29 ± 0.032 μg/kg body weight). They underwent clinical and laboratory investigation and were questioned with regard to potential adverse reactions immediately and three days after administration of DDAVP.: Results, conclusion: Most adverse reactions were mild and no serious adverse drug reactions were either observed or reported by the subjects. We identified significant changes of heart rate, blood pressure and leucocytes after conduct of the DDAVP test. The value of these findings has to be investigated in later prospective randomized studies. Further research on identification of prospective parameter is currently ongoing.

scholarly journals Replacement Therapy in Patients with Von Willebrand Disease—Indications and Monitoring

2019 ◽  
Vol 39 (04) ◽  
pp. 326-338
Author(s):  
Ulrike Nowak-Göttl ◽  
Wolfgang Miesbach ◽  
Jürgen Koscielny ◽  
Carl-Erik Dempfle ◽  
Marc Maegele ◽  
...  
Keyword(s):  
Replacement Therapy ◽  
Von Willebrand Disease ◽  
Spontaneous Bleeding ◽  
Surgical Interventions ◽  
Bleeding Episodes ◽  
Repeated Dosing ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Trough Levels ◽  
Very High

AbstractIn patients with von Willebrand disease (VWD), replacement therapy may be indicated in the case of spontaneous bleeding, surgical interventions and injuries/trauma or as a prophylaxis of spontaneous bleeding episodes. The deficient von Willebrand factor (VWF) is replaced with or without factor VIII (FVIII). Dual VWF/FVIII concentrates can be beneficial in the case of low FVIII level, while repeated dosing may lead to very high FVIII levels, with a potential thrombogenic effect in individual VWD patients. An excessive FVIII:C increase can be limited by using a VWF product with a low level of FVIII, achieving a haemostatic adequate FVIII:C increase after 6 to 12 hours. Replacement therapy in patients with VWD shall be individualised considering VWD type, history and risk of bleeding and risk of thrombosis, as well as indication and the individually variable VWF and FVIII increase. Deviations from the dosages and minimum trough levels mentioned in guidelines or recommendations can be considered in justified cases. The objective of this review is to provide recommendations for specific constellations of replacement therapy based on the VWD-specific guidelines available in Europe, the available evidence, own experiences and the consensus of the interdisciplinary German author group.

Incidence and Determinants of Bleeding in Different Types of von Willebrand Disease: Results of the First Prospective Multicenter Study on 814 Italian Patients.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 713-713 ◽  
Author(s):  
Augusto B. Federici ◽  
Paolo Bucciarelli ◽  
Giancarlo Castaman ◽  
Maria G. Mazzucconi ◽  
Massimo Morfini ◽  
...  
Keyword(s):  
Prospective Study ◽  
Von Willebrand Disease ◽  
Free Survival ◽  
Risk Of Bleeding ◽  
Bleeding Episodes ◽  
Mucosal Bleeding ◽  
One Year ◽  
Type 3 ◽  
Von Willebrand

Abstract Background. von Willebrand disease (VWD) is the most common inherited bleeding disorder and is due to quantitative and/or qualitative defects of von Willebrand factor (VWF). Despite the improved knowledge of the disorder, no data on the incidence and determinants of bleedings requiring specific treatments have been available thus far. Aims and design of the study: to determine the incidence and determinants of bleedings requiring therapy with DDAVP and/or VWF concentrates in VWD, a national registry was organized by using a database devised to collect detailed retrospective information. Patients included in the registry were followed up for one year and prospective data on number, type and management of bleeding episodes were analyzed. Methods: all patients were diagnosed following recommendations of the ISTH-SSC-SC on VWF with bleeding severity score (BSS) calculated at enrollment. Diagnoses of VWD were confirmed by the coordinating center using also multimeric analysis in plasma and mutations of VWF gene in all types 2 and 3. For different risk categories the incidence of bleeding (mucosal and non-mucosal bleeding) was calculated. Bleeding-free survival was computed with the Kaplan-Meier method and a Cox’s proportional hazard model was used to calculate the risk of bleeding (hazard ratio = HR) Results: In the retrospective study, 1,234/1,529 (81%) cases satisfied the inclusion criteria and were enrolled in the registry as types 1 (54%), 2 (40%) and 3 (6%).VWD diagnosis occurs in young adults (83%), mainly in women (57%). Mucosal bleeding (64%) are more frequent than hematomas or hemarthrosis (15%) but 73% of patients did not require transfusions. In the prospective study based on 814/1,234 (66%) cases of the registry (type 1=47%, 2=47%, 3=6%) 147/815 (18%) were treated in a year for 318 bleeding episodes and 87 minor or major surgeries. BSS >10 (6.8, 3.8–12.3), bleeding time >20 min (BT = 5.5, 3.1–9.8), VWF:RCo <10 U/dL (3.2, 1.7–5.9) and FVIII:C <20 U/dL (4.1, 2.4–7) were significantly associated with high risk of bleeding. By multivariate model including all the variables, BSS (5.5, 2.8–10.8) was the most significant determinant of bleeding. The bleeding-free survival at one year was significantly different in type 3 (52%) versus types 1 (96%) and 2 (91%) VWD. On the other hands, patients with VWF.RCo >30 U/dL and FVIII:C > 40 U/dL showed always BSS <5 with the lowest incidence of bleeding. A total of 292 DDAVP injections were used to manage bleeding and surgeries in types 1 (65%) and 2 (35%) VWD and 452 injections of VWF concentrates were used to treat bleeding and surgeries in type 3 (75%), type 2 (34%) and type 1 (15%) VWD. Conclusions: This prospective study confirms that BSS is an important predictive factor for clinical bleeding and the need for treatment. In cases with VWF.RCo >30 U/dL and FVIII:C >40 U/dL bleeding episodes are very rare, in agreement with their relatively low BSS.

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