Cost Effectiveness Strategy to Predict Postoperative Bleeding in Von Willebrand Disease.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1295-1295
Author(s):  
Daniel Delitto ◽  
Margaret V. Ragni ◽  
Kenneth J Smith
Keyword(s):  
Cost Effectiveness ◽  
Incremental Cost ◽  
Postoperative Bleeding ◽  
Bleeding Risk ◽  
Von Willebrand Disease ◽  
Test Series ◽  
Surgical Bleeding ◽  
Bleeding History ◽  
Von Willebrand

Abstract Von Willebrand disease (VWD) is the most common congenital bleeding disorder, affecting up to 1% of the population. In type 1 VWD, which accounts for 65% of the disease, bleeding may be mild and up to 50% may have a normal screening APTT. Thus, in many the diagnosis may be missed and excess bleeding may occur postoperatively, which could potentially be prevented if reliable preoperative predictors existed. In order to assess possible predictors of postoperative bleeding and determine a cost-effective strategy to predict postoperative bleeding in patients with type 1 VWD, we constructed a decision tree model to test various screening strategies, including bleeding severity score (BSS), VWD assays (VWF:RCo; VWF:Ag, VIII:C), platelet function (PFA-100), and family bleeding history (Fam Hx), alone and in combination, in various sequence. For the model, sensitivity and specificity of coagulation tests, BSS, and family bleeding history were determined on 129 subjects with type 1 VWD, including 74 experiencing postoperative bleeding prior to diagnosis and 55 experiencing no postoperative bleeding prior to diagnosis. BSS was determined for each subject at the time of diagnosis (but prior to surgical bleeding), based on abstracted outpatient medical records. Testing, transfusion, and hospitalization costs were based on local costs, and DDAVP cost was based on average wholesale price. Outcomes were testing strategy cost and strategy effectiveness, as measured by postoperative bleeding risk. It was assumed that all patents testing positive, based on a given strategy, would receive preoperative DDAVP and be 100% protected from bleeding; and that those who developed postoperative bleeding would require three days of hospitalization and receive a transfusion. In the base case analysis, with VWD prevalence of 1%, BSS 3 3 and the Test Series (any of VWF:RCo VWF:Ag, F.VIII) dominates over all other strategies, based on having the highest sensitivity. When prevalence is varied 0–1%, the strategy of BSS 3 3 and the Test Series seems a reasonable choice if prevalence is 3 1%. At 1% prevalence, the incremental cost-effectiveness ratio (ICER) is about $103,000 which is at the edge of what may be considered economically reasonable. However, the ICER, for this strategy falls fairly rapidly, and is < $100,000 when prevalence is 3 1.03%. We also varied the proportion requiring hospitalization or transfusion to 5% and 1%, respectively, but these did not significantly affect the results. In conclusion, in individuals with BSS 3 3, proceeding with the Test Series (VWF:RCo, VWF:Ag, F.VIII) is a clinically and economically reasonable strategy for those in whom DDAVP should be given to prevent surgical bleeding, when the bleeding risk is 3 1%. Strategy Cost Incremental Cost Effectiveness Incremental Effectiveness ICER BSS ≥ 3 & Test Series $1,296.10 0.055 Fam Hx $1,703.90 $407.70 0.087 −0.032 (Dominated) Fam Hx & Test Series $2,187.50 $891.40 0.111 −0.056 (Dominated) Fam Hx or BSS ≥ 3 & Test Series $2.435.40 $1,139.30 0.127 −0.072 (Dominated) Test Series $2,508.60 $1,212.50 0.132 −0.077 (Dominated) BSS ≥ 3 $2.974.30 $1,678.10 0.171 −0.116 (Dominated) BSS ≥ 5 $5,966.10 $4.669.90 0.364 −0.309 (Dominated) No Testing or Rx $9,238.30 $7.942.20 0.574 −0.519 (Dominated)

Bleeding Score as a Preoperative Predictor of Postoperative Bleeding in Type 1 Von Willebrand Disease.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1019-1019 ◽  
Author(s):  
Laura R. Goldberg ◽  
Margaret V. Ragni
Keyword(s):  
Family History ◽  
Postoperative Bleeding ◽  
Von Willebrand Disease ◽  
Chi Square ◽  
Exact Test ◽  
Bleeding Score ◽  
Chi Square Analysis ◽  
Bleeding History ◽  
Von Willebrand

Abstract Type 1 Von Willebrand Disease (VWD) is the most common congenital bleeding disorder, affecting 1% of the population, and caused by a quantitative deficiency of Von Willebrand Factor (VWF). In addition to mucosal bleeding, VWD patients often suffer postoperative bleeding, leading to significant morbidity. Thus, a preoperative diagnosis could potentially reduce postoperative bleeding. Because symptoms correlate poorly with VWD assays, subject to extragenic effects and lab variability, diagnosis is difficult. The bleeding score (BS) is a simple quantitative tool recently developed to rate bleeding symptom severity, with 99% specificity for VWD. To determine the potential utility of BS in predicting postoperative bleeding in VWD, we evaluated preoperative BS by retrospective review of type 1 VWD patients who suffered postoperative bleeding prior to diagnosis. Preoperative clinical bleeding symptoms and VWD assays, including VWF:RCo, VWF:Ag, and FVIII:C, were obtained. The severity of clinical bleeding symptoms present prior to surgery was rated by the 4-point BS scale: 0 = no/trivial; 1 = present; 2 = intervention required; 3 = replacement therapy. Statistical analysis was by chi square analysis and Fisher’s exact test for categorical data, and by student t test for continuous data. Of 260 registered type 1 VWD patients, 71 (27.3 %) experienced surgical bleeding prior to a diagnosis of VWD. Of these 56 (78.9%) were female, 48 (67.6%) were adults (≥ 18 yr), and 61 (85.9%) had a family bleeding history. The surgeries included general, gynecologic, genitourinary, and otolaryngologic procedures. The median preop BS, 3 in females and 4 in adults, was significantly higher than in males and children, each median 1, p<0.01, respectively. A BS ≥ 3 would have identified only 59.1% patients before surgery, but as many as 90.1%, if combined with one abnormal VWD test; 94.4%, with family bleeding history; or 97.2% with both family history and one abnormal VWD test. The proportion of children identified by BS was significantly lower than in adults, 26.1% vs 75.0 % with BS > 3, p = 0.001. Yet this significantly improved by combining BS with family history, 91.3% vs 95.8%, not different from adults, p = 0.591. We conclude that obtaining a preoperative BS and family bleeding history may reduce postoperative bleeding and promote timely diagnosis among individuals with type 1 VWD patients, particularly children. Preoperative Bleeding Score in Type 1 VWD Patients with Postoperative Bleeding Male Female Age < 18 Age ≥ 18 All N = 15 N = 56 N = 23 N = 48 N = 71 τp = .001, as compared with under 18 yr; σp = .007, as compared with males; ζ p > 0.5 as compared with age under 18 or males, respectively. BS≥1 10/15 (66.7%) 54/56 (96.4%) 18/23 (78.3%) 46/48 (95.8%) 64/71 (90.1%) BS≥3 4/15 (26.7%) 38/56 (67.8%)σ 6/23 (26.1%) 36/48 (75.0%)τ 42/71 (59.1%) BS≥5 2/15 (13.3%) 17/56 (30.3%) 2/23 (8.7%) 17/48 (35.4%) 19/71 (26.7%) Abnl VWF:RCo 8/15 (53.3%) 19/56 (33.9%) 6/23 (26.1%) 19/48 (39.6%) 27/71 (38.0%) Abnl VWD Test 11/15 (73.3%) 41/56 (73.2%) 16/23 (69.6%) 36/48 (75.0%) 52/71 (73.2%) Fam Bld History 15/15 (100%) 47/56 (83.9%) 21/23 (91.3%) 40/48 (83.3%) 61/71 (85.9%) BS≥3 ± Abnl VWD Test 13/15 (86.7%) 51/56 (91.1%) 18/23 (78.3%) 46/48 (95.8%) 64/71 (90.1%) BS≥3 ± Fam Hx 15/15 (100.0%) 52/56 (92.8%)ζ 21/23 (91.3%) 46/48 (95.8%)ζ 67/71 (94.4%) BS≥3 ± Fam Hx ± Abnl VWD Test 15/15 (100.0%) 54/56 (96.4%) 22/23 (95.6%) 47/48 (97.9%) 69/71 (97.2%)

Toward Personalized Treatment for Patients with Low von Willebrand Factor and Quantitative von Willebrand Disease

2021 ◽  
Vol 47 (02) ◽  
pp. 192-200
Author(s):  
James S. O'Donnell
Keyword(s):  
Von Willebrand Factor ◽  
Bleeding Risk ◽  
Von Willebrand Disease ◽  
Personalized Treatment ◽  
Treatment Plans ◽  
Type 3 ◽  
Von Willebrand ◽  
Willebrand Factor

AbstractThe biological mechanisms involved in the pathogenesis of type 2 and type 3 von Willebrand disease (VWD) have been studied extensively. In contrast, although accounting for the majority of VWD cases, the pathobiology underlying partial quantitative VWD has remained somewhat elusive. However, important insights have been attained following several recent cohort studies that have investigated mechanisms in patients with type 1 VWD and low von Willebrand factor (VWF), respectively. These studies have demonstrated that reduced plasma VWF levels may result from either (1) decreased VWF biosynthesis and/or secretion in endothelial cells and (2) pathological increased VWF clearance. In addition, it has become clear that some patients with only mild to moderate reductions in plasma VWF levels in the 30 to 50 IU/dL range may have significant bleeding phenotypes. Importantly in these low VWF patients, bleeding risk fails to correlate with plasma VWF levels and inheritance is typically independent of the VWF gene. Although plasma VWF levels may increase to > 50 IU/dL with progressive aging or pregnancy in these subjects, emerging data suggest that this apparent normalization in VWF levels does not necessarily equate to a complete correction in bleeding phenotype in patients with partial quantitative VWD. In this review, these recent advances in our understanding of quantitative VWD pathogenesis are discussed. Furthermore, the translational implications of these emerging findings are considered, particularly with respect to designing personalized treatment plans for VWD patients undergoing elective procedures.

scholarly journals Impact of Two Immobilized GPIbα Assays in the Diagnosis of Von Willebrand Disease

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1524-1524
Author(s):  
Silmara Lima Montalvão ◽  
Sandra Martins Silva Soares ◽  
Marina P Colella ◽  
Joyce M Annichino-Bizzacchi ◽  
Samuel de Souza Medina ◽  
...  
Keyword(s):  
Sensitivity And Specificity ◽  
False Positive ◽  
New Technologies ◽  
Von Willebrand Disease ◽  
The Other ◽  
Bleeding Score ◽  
Bleeding History ◽  
Von Willebrand ◽  
Positive Results

Abstract The diagnosis of von Willebrand Disease (VWD) remains a challenge of daily hematology practice. Ristocetin cofactor activity (VWF:RCo) is an important parameter for the diagnosis of VWD and is also essential for its management. However, reproducibility of the available tests for VWF:RCo is still a major issue, as evidenced by coefficient of variations (CV) as high as 30%, 45% and 27% in the ECAT, NEQAS and PALQ external quality assessment program. Classical methods to measure VWF:RCo include light-transmission platelet agregometry (LPA) and visual agglutination with formaldehyde fixed human platelet (VA), and more recently, VWF activity based on automated latex immunoassay (LIA). The glycoprotein (GP) Ibα is the main receptor for von Willebrand factor (VWF) in the platelet membrane. Currently, two automated methods with immobilized GPIbα have been developed to improve the sensitivity and specificity of VWF:RCo. One of them is performed with ristocetin while the other one uses a mutant GPIbα with gain of function and does not require ristocetin. This study aims to compare the two assays using immobilized GPIbα with other four assays for VWF functional determination, in patients with confirmed and under investigation for VWD. We evaluated six different VWF functional assays: VWF:RCo LPA (Chrono-Log); VA (Siemens); VA in house (with ristocetin from Chrono-Log); automated-LIA (Hemosil); in comparison to two assays using immobilized GPIbα with or without ristocetin, the GPIbα-ristocetin (Hemosil), and GPIbα-mutant (Siemens Innovance). Reference ranges for each method were established in 20 healthy adults. Plasma samples collected at the same time from 40 individuals were used in this comparative study, with 25 type 1 VWD, 2 type 3 VWD, and 13 under investigation. Diagnosis of VWD was based on bleeding history (evaluated by MCMDM-1VWD Bleeding Score), historical levels of VWF antigen (VWF:Ag) by ELISA, and VWF:RCo (assayed by LTA or VA) obtained from medical records. Statistical analysis were performed based on linear regression (Spearman correlation), agreement test (Altman Bland), and chi-square test using Prism 6.0. When all 40 patients were evaluated for both methods, GPIbα-ristocetin and GPIbα-mutant, we observed a good coefficient of correlation (r = 0.8954; p<0.0001). However, when 7 type 1 VWD patients, and 1 under investigation case were evaluated for the six methods, the two using immobilized GPIbα showed lower median (16.78 ± 4.62 with GPIbα-ristocetin, and 16.28 ± 4.29 with GPIbα-mutant), when compared with the other four assays (LTA: 22.38 ± 5.5; VA in house: 21.45 ± 4.87; VA Siemens: 22.65 ± 4.9; and LIA: 24.19 ± 9.0). In this group, when the bleeding score (BS) were ≥ 5, the VWF functional results were lower than 25 IU/dL, using all six methods (figure). Among 13 individuals under VWD investigation, GPIbα-ristocetin and GPIbα-mutant showed good agreement with the LTA/VA results and clinical history, and we could concluded that 4 have VWD, and for 4 individuals VWD was excluded. However, 2 individuals with no history of bleeding presented abnormal results for GPIbα-ristocetin and GPIbα-mutant, showing probably false positive results. One patient with no bleeding history, and abnormal LTA/VA results had normal GPIbα-ristocetin and GPIbα-mutant results, demonstrating poor reproducibility and precisian of the classical methods. On the other hand, two patient with BS 6, the diagnosis of VWD was demonstrating only by immobilized GPIbα methods. The VWF:RCo is a cumbersome assay and can be affected by polymorphisms present in the ristocetin binding site of VWF. Recently, new technologies have been developed to improve the VWF functional evaluation. It is consensus that methodologies using platelets are more accurate than other methods. Therefore, immobilized GPIbα has the objective to improve the sensitivity and specificity. Besides good results of concordance between immobilized GPIbα in the group of VWD patients and for 62% individual under investigation, we also observed false positive results related with these methods. The presence or absence of ristocetin on the immobilized GPIbα setting appear not engender different results in this study. In general, this new technologies present better precision compared to VA and LTA. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Experience with Epidural Anesthesia in Pregnant Women with Von Willebrand Disease.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1026-1026
Author(s):  
Jay Varughese ◽  
Alice J. Cohen
Keyword(s):  
Pregnant Women ◽  
Von Willebrand Factor ◽  
Epidural Anesthesia ◽  
Postpartum Hemorrhage ◽  
Postoperative Bleeding ◽  
Von Willebrand Disease ◽  
Bleeding Complications ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract Von Willebrand Disease (vWD) is an autosomal dominant inherited bleeding disorder that is characterized by epistaxis, mucosal and postoperative bleeding, menorrhagia and postpartum hemorrhage. In particular, there is a paucity of safety data for, and thus a reluctance to use, epidural anesthesia (EA) for delivery. We thus conducted a review of all women followed with vWD in a referral hemophilia clinic who had ≥ 1 pregnancy. Thirty-three subjects were screened; 31/33 (94%) had type 1 and 2/33 (6%) had type 2A vWD. There were 59 term pregnancies (range 1–3 per patient), and 5 fetal losses (in 4 patients). Of the term pregnancies, 16/59 (27%) were delivered by Caesarian Section (C-Section), complicated by postpartum hemorrhage in 3 (19%); 43/59 (73%) were delivered by normal spontaneous vaginal delivery (NSVD), complicated by hemorrhage in 21 (49%) (p=0.05). EA was administered during 14 (13 with type 1 vWD) of 59 (24%) of the deliveries, all without DDAVP, plama-derived factor VIII-von Willebrand factor containing concentrates or blood products, and in no patient were bleeding complications encountered at the site of EA nor were there any neurologic complications. Conclusion: Postpartum hemorrhage was a common complication in patients with vWD, more after NSVD than C-Section. In a selected subset, EA was safely administered without bleeding complications, possibly due to pregnancy induced increase in factor VIII:C and von Willebrand factor activity counteracting the tendency to bleed. Larger series and prospective studies should be performed to confirm the safety of EA and the relationship to coagulation factor levels in pregnant women with vWD.

Phase II Biologic Effects Trial of Recombinant Interleukin-11 (rhIL-11, Neumega) in Moderate or Mild Hemophilia A or Von Willebrand Disease Unable to Use DDAVP,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3308-3308
Author(s):  
Margaret V. Ragni ◽  
Enrico M. Novelli ◽  
Anila Murshed ◽  
Elizabeth P. Merricks ◽  
Mark T. Kloos ◽  
...  
Keyword(s):  
Phase Ii ◽  
Hemophilia A ◽  
Conflicts Of Interest ◽  
Postoperative Bleeding ◽  
Fold Increase ◽  
Von Willebrand Disease ◽  
Fluid Restriction ◽  
Biologic Effects ◽  
Von Willebrand

Abstract Abstract 3308 Background: DDAVP is the treatment of choice for individuals with type 1 von Willebrand disease (VWD), although 20% are unresponsive, and of the 80% who do respond, the VWF increase is transient, as endothelial stores are depleted after 3 days. Further, administration requires a 30- minute intravenous infusion in a medical facility. Plasma-derived concentrates may be used in these settings, but are more costly and have potential risk of transmissible infection. We recently demonstrated that recombinant human IL-11 (rhIL-11, Neumega®), a gp-130 signaling cytokine with hematopoietic and anti-inflammatory activity, increases VWF activity up to 2-fold when given daily by subcutaneous injection, with levels persisting each day it is given, and reduces menstrual and postoperative bleeding. The effects of rhIL-11 in individuals with VWD unresponsive or allergic to DDAVP, or hemophilia A, however, have not been evaluated. Methods: We conducted a phase II trial to evaluate the safety and biologic effects of rhIL-11 in VWD patients unresponsive or allergic to DDAVP (VWD-Un) or mild hemophilia A (HemA). rhIL-11 was given subcutaneously at 25 μg/kg daily for 4 days in the non-bleeding state, followed on day 4, 30 minutes after rhIL-11, by one dose of DDAVP intravenously, 0.3 μg/kg, if not contraindicated (pt. 2). Fluid restriction was recommended. Fluid status was assessed by height, weight, and exam. Pre- and post-dosing laboratory assays included the VWD profile, VWF multimers by SDS gel electrophoresis, and platelet VWF mRNA by qPCR. Results: The results of the first six subjects, including three with VWD (one type IIB and two type 1 VWD), VWF:RCo 0.10–0.20 U/ml, and three with mild hemophilia A, F.VIII 0.08–0.12 U/ml, are presented. All subjects were healthy, with no hypertension or cardiac disease, and all had normal physical exams and normal EKGs. By day 4, among VWD-Un subjects, there was a 1.2-fold increase in VWF:RCo (15±3% vs. 12±0%); a 1.6-fold increase in VWF:Ag (22±8% vs.14±6%); and a 1.3-fold increase in VIII:C (34±36% vs. 27±10%), as compared with pre-rhIL-11 levels (Figure). Following DDAVP (except pt. 2), there was an additional 2.0-fold, 1.7-fold, and 2.6-fold increase in VWF:RCo, VWF:Ag, and VIII:C, respectively. Among HemA subjects, by day 4, there was a 1.8-fold increase in VWF:RCo (160±25% vs. 88±12%); a 1.8-fold increase in VWF:Ag (182±28% vs.99±18%), p<0.01; and a 1.5-fold increase in VIII:C (21±8% vs. 14±5%), as compared with pre-rhIL-11 levels. Following DDAVP, there was an additional 1.5-fold (p<0.01), 1.7-fold, and 2.8-fold (p<0.05) increase in VWF:RCo, VWF:Ag, and VIII:C, respectively. The drug was well tolerated well with less than grade 1 mild conjunctival erythema, local erythema and tenderness at the injection site; in one subject transient hyponatremia, Na 129 meq/L, occurred after excess oral fluid intake for diabetic hyperglycemia, which resolved with fluid restriction. Discussion: These data suggest that rhIL-11 increases VWF and VIII levels modestly in VWD patients unresponsive/allergic to DDAVP, and in mild hemophilia A, suggesting the potential use in treatment of clinical bleeding in these disorders. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Bleeding Outcomes in People with Von Willebrand Disease Receiving Antithrombotic Therapy

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3196-3196
Author(s):  
Aisling Barrett ◽  
Catherine Bergin ◽  
Mary Byrne ◽  
Kevin Ryan ◽  
Niamh M O'Connell ◽  
...  
Keyword(s):  
Antithrombotic Therapy ◽  
Bleeding Risk ◽  
Von Willebrand Disease ◽  
Cumulative Exposure ◽  
Bleeding Complications ◽  
Gi Bleeding ◽  
Von Willebrand

Abstract Aging brings additional challenges in the management of people with von Willebrand Disease (VWD). Plasma von Willebrand Factor (VWF) levels may increase but the impact on bleeding phenotype is unclear. With the development of age-related comorbidities, the use of antiplatelet (AP) or anticoagulant (AC) therapies may be warranted. As highlighted in the 2021 international VWD guidelines, limited evidence exists regarding the bleeding risk and safety of AP/AC use in people with VWD. 1 We sought to address this knowledge gap through a retrospective review of a large cohort of people with VWD attending a tertiary referral center. The records of all patients aged &gt;50 years (y) attending our center registered with VWD were retrospectively reviewed. We identified all individuals treated with AP and/or AC, recording the indication for and duration of therapy. We also recorded disease subtype, baseline and most recent plasma VWF levels and bleeding on AP and/or AC. Bleeding episodes were stratified according to the World Health Organization (WHO) Bleeding Scale. From 255 eligible patients, 18 patients (7 male, 11 female) were identified who received AP and/or AC over a period of 22y. The median age at commencement was 60.2 years (range 40.0-74.5). 15 patients had Type 1 with baseline levels 30-50 IU/dL, (median VWF antigen, VWF:Ag, 57.5, range 39-87 IU/dL; median VWF ristocetin cofactor levels, VWF:RCo, 43, range 35-54 IU/dL). 3 patients had type 2 VWD (median VWF:Ag 64, range 27-90 IU/dL; median VWF:RCo of 16, range 10-66 IU/dL). The type of AP/AC used and indications for treatment are outlined in Table 1. Overall, 12 patients were treated with AP and 7 with AC therapy (19 therapies in total as one patient received first aspirin then warfarin therapy). The cumulative exposure to AP therapy was 61.9y with a median exposure time of 3.2y/patient (range 0.3-14.1y). Duration of AC therapy was shorter, with a cumulative exposure of 17.6y and a median of 1.5 y/patient (range 0.3-6.3y). Overall, 85.7% of patients on AC therapy had at least one episode of bleeding (6/7; 10 episodes total) in contrast to 58.3% of patients on AP (7/12; 12 episodes total). Of these 22 episodes, 5 (22.7%) were grade 1 bleeding. Grade 2 bleeding (iron deficiency or gastrointestinal (GI), gynecological or genitourinary bleeding) occurred in 5 patients (41.7%) treated with AP and 4 patients (57.1%) on AC (total of 14 episodes). 1 episode of grade 3 bleeding occurred in both the AP (8.3%) and AC (14.3%) group (GI bleeding requiring transfusion and abdominal hematoma respectively). The single grade 4 bleed was an intracranial hemorrhage (ICH) and occurred in a patient with type 2 VWD (VWF:RCo 10 IU/dL) on warfarin for atrial fibrillation; this required prothrombin complex concentrate, VWF concentrate, neurosurgical intervention and cessation of AC. Bleeding complications resulted in discontinuation of therapy in 2 patients (11.1%) treated; the individual with ICH and a patient with type 1 VWD on warfarin (baseline VWF:RCo 43 IU/dL) due to recurrent GI bleeding. No patients treated with AP therapy required discontinuation of use. The overall rate of major bleeding (WHO grade &gt;/=3) in our study was 11.4 events/100 patient-years in VWD patients receiving AC therapy, in comparison to the rate of bleeding in the general population using AC of 7.2 events per 100 patient-years. 2 For patients with type 1 VWD, plasma VWF levels were seen to increase during follow up (median 8.5y, VWF:Ag median +13 IU/dL, VWF:RCo +18 IU/dL), resulting in plasma VWF levels &gt;50 IU/dL for 66.6% of patients in this cohort. Despite this, bleeding while on AP and/or AC was still experienced in 8/10 patients whose levels had normalized, necessitating cessation in one instance. In conclusion, this study provides important insights into the use of AP and/or AC in patients with VWD. Bleeding rates were higher in patients treated with AC therapy than AP resulting in cessation of therapy in 28.6% of those on AC. Bleeding events still occurred despite normalization of plasma VWF levels in patients with type 1 VWD. These data highlight the need for close follow up of patients with VWD whilst on antithrombotic therapy, particularly AC. 1. Connell NT et al. ASH ISTH NHF WFH 2021 guidelines on the management of von Willebrand disease. Blood Adv 2021;5(1):301-325. 2. Shoeb M, Fang M. Assessing Bleeding Risk in Patients Taking Anticoagulants. J Thromb Thrombolysis 2013;35(3):312-319. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Combined Hereditary Disorders of Haemophilia B Leyden (-6 G → A) and Type 1 von Willebrand Disease

1996 ◽  
Vol 76 (02) ◽  
pp. 151-155 ◽  
Author(s):  
Gilles Pernod ◽  
Christine Vinciguerra ◽  
Christine Gaucher ◽  
Claudine Mazurier ◽  
Benoît Polack ◽  
...  
Keyword(s):  
Bleeding Risk ◽  
Von Willebrand Disease ◽  
Factor Ix ◽  
Haemophilia B ◽  
Age Related ◽  
Hereditary Disorders ◽  
Paternal Grandmother ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryMultiple coagulation disorders are unusual. We report here a combination of haemophilia B Leyden with type 1 von Willebrand disease (vWD) affecting different members of the same family. Haemophilia B Leyden was due to a -6 G → A mutation within the promoter of the factor IX gene and was responsible for a mild haemophilia in the father of the proband. The proband and her sister (age 4 and 6) exhibited a twofold lower level of factor IX activity (0.4 IU/ml) than the paternal grandmother (0.95 IU/ml). The differences in FIX levels in the three carriers of the same -6 G → A mutation suggest the implication of an age-related mechanism responsible for the increase in factor IX plasma level. Haemophilia B Leyden patient and carriers suffered also from a mild von Willebrand disease. The diagnosis of this associated type 1 vWD was performed by assaying plasma von Willebrand factor together with multimer electrophoretic studies and DDAVP test. The inheritance of this vWD was investigated by haplotype analysis of the vWF gene. Individuals affected by such an association are actually asymptomatic, but per- and post-operative bleeding risk remains to be evaluated.

scholarly journals Perioperative management of patients with von Willebrand disease

Hematology ◽  
2019 ◽  
Vol 2019 (1) ◽  
pp. 604-609 ◽  
Author(s):  
James S. O’Donnell ◽  
Michelle Lavin
Keyword(s):  
Best Practice ◽  
Perioperative Management ◽  
Bleeding Risk ◽  
Von Willebrand Disease ◽  
Major Surgery ◽  
Best Practice Guidelines ◽  
Frequent Monitoring ◽  
Bleeding History ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract Surgical procedures represent a serious hemostatic challenge for patients with von Willebrand disease (VWD), and careful perioperative management is required to minimize bleeding risk. Risk stratification includes not only the nature of the surgery to be performed but the baseline plasma von Willebrand factor (VWF) levels, bleeding history, and responses to previous challenges. Baseline bleeding scores (BSs) may assist in identification of patients with a higher risk of postsurgical bleeding. There remains a lack of consensus between best practice guidelines as to the therapeutic target and assays to be monitored in the postoperative period. Hemostatic levels are maintained until bleeding risk abates: usually 3 to 5 days for minor procedures and 7 to 14 days for major surgery. Hemostatic supplementation is more complex in VWD than in other bleeding disorders owing to the combined but variable deficiency of both plasma VWF and factor VIII (FVIII) levels. For emergency surgery, coadministration of VWF and FVIII is required to ensure hemostasis; however, for elective procedures, early infusion of VWF replacement therapy will stabilize endogenous FVIII. Because endogenous FVIII production is unaffected in patients with VWD, repeated VWF supplementation (particularly with plasma-derived FVIII-containing products) may lead to accumulation of FVIII. Frequent monitoring of plasma levels and access to hemostatic testing are, therefore, essential for patients undergoing major surgery, particularly with more severe forms of VWD.

scholarly journals Bleeding Symptoms and von Willebrand Factor Levels: 30-Year Experience in a Tertiary Care Center

2019 ◽  
Vol 25 ◽  
pp. 107602961986691
Author(s):  
Chatphatai Moonla ◽  
Benjaporn Akkawat ◽  
Yaowaree Kittikalayawong ◽  
Autcharaporn Sukperm ◽  
Mukmanee Meesanun ◽  
...  
Keyword(s):  
Von Willebrand Factor ◽  
Care Center ◽  
Tertiary Care ◽  
Bleeding Risk ◽  
Binding Activity ◽  
Von Willebrand Disease ◽  
Von Willebrand ◽  
Willebrand Factor

Correlations between bleeding symptoms and von Willebrand factor (VWF) levels may help to predict hemorrhagic severity in the Westerners with von Willebrand disease (VWD), but data in Asians are lacking. In this study, Thai patients with VWF levels <50 IU/dL without any secondary causes were enrolled from 1988 to 2018 to determine the relationship between VWF levels and hemorrhagic manifestations. According to the current concept, we reclassified VWD and low VWF by VWF levels ≤30 and 30 to 50 IU/dL, respectively. Type 2 VWD was diagnosed if VWF activity to antigen ratio was ≤0.6. Bleeding severity was determined by the condensed MCMDM-1VWD bleeding score (BS). Among 83 patients, VWF activities showed negative correlations with BS ( P = .001), which were higher in type 2 (median: 7, interquartile range [IQR]: 5-11) compared with type 1 VWD (median: 3, IQR: 2-4) and low VWF (median: 4, IQR: 2-8). Bleeding symptoms were indistinguishable between type 1 VWD and low VWF using the 30 IU/dL cutoff point. However, VWF ristocetin cofactor activity or gain-of-function mutant glycoprotein Ib binding activity <36.5 IU/dL and VWF collagen binding activity <34.5 IU/dL could predict increased bleeding risk (BS ≥3) by 92.3% specificity and 70.0% sensitivity ( P < .0001).

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