Testing for von Willebrand Disease in Women With Menorrhagia: A Systematic Review

Background: Von Willebrand Disease (VWD) can be associated with significant morbidity. Patients with VWD can experience bruising, mucocutaneous bleeding, and bleeding after dental and surgical procedures. Early diagnosis and treatment are important to minimize the risk of these complications. Several bleeding assessment tools (BATs) have been used to quantify bleeding symptoms as a screening tool for VWD. Objective: We systematically reviewed diagnostic test accuracy results of bleeding assessment tools (BATs) to screen patients for VWD. Methods: We searched Cochrane Central, MEDLINE, and EMBASE for eligible studies, reference lists of relevant reviews, registered trials, and relevant conference proceedings. Two investigators screened and abstracted data. Risk of bias was assessed using QUADAS-2 and certainty of evidence using the GRADE framework. We pooled estimates of sensitivity and specificity. Results: The review included 7 cohort studies that evaluated the use of BATs to screen adult and pediatric patients for VWD. The pooled estimates for sensitivity and specificity were 75% (95% confidence interval [CI] 66%-83%) and 54% (29%-77%), respectively. Certainty of evidence varied from moderate to high. Conclusion: This systematic review provides accuracy estimates for validated BATs as a screening modality for VWD. A BAT is a useful initial screening test to determine who needs specific blood testing. The pretest probability of VWD (often determined by the clinical setting/patient population), along with sensitivity and specificity estimates will influence patient management.

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Von Willebrand Factor Levels in The Diagnosis of Von Willebrand Disease: A Systematic Review and Meta-Analysis

Blood Advances ◽

10.1182/bloodadvances.2021005430 ◽

2021 ◽

Author(s):

Mohamad A. Kalot ◽

Nedaa Husainat ◽

Abdallah El Alayli ◽

Omar Abughanimeh ◽

Osama Diab ◽

...

Keyword(s):

Systematic Review ◽

Meta Analysis ◽

Health Benefit ◽

Von Willebrand Disease ◽

Test Accuracy ◽

Sequence Variants ◽

Continuous Variables ◽

Von Willebrand

Von Willebrand Disease (VWD) is associated with significant morbidity as a result of excessive mucocutaneous bleeding symptoms. Patients with VWD can experience easy bruising, epistaxis, gastrointestinal and oral cavity bleeding, as well as heavy menstrual bleeding and bleeding after dental work, surgical procedures, and childbirth. Early diagnosis and treatment is important to prevent and treat these symptoms. We systematically reviewed the accuracy of diagnostic tests using different cut-off values of VWF:Ag and platelet-dependent VWF activity assays in the diagnosis of VWD. We searched Cochrane Central, MEDLINE, and EMBASE for eligible studies. Two investigators screened and abstracted data. Risk of bias was assessed using QUADAS-2 and certainty of evidence using the GRADE framework. We pooled estimates of sensitivity and specificity and reported patient important outcomes when relevant. This review included 21 studies that evaluated VWD diagnosis, including the approach to patients with VWF levels that have normalized with age (6 studies), VWF cut-off levels for the diagnosis of Type 1 VWD (9 studies), and platelet-dependent VWF activity/VWF:Ag ratio cut-off levels for the diagnosis of Type 2 VWD (6 studies). The results showed low certainty in the evidence for a net health benefit from reconsidering the diagnosis of VWD versus simply removing the disease in patients with VWF levels that have normalized with age. For the diagnosis of Type 1 VWD, in patients with VWF:Ag <0.30 IU/mL, VWF sequence variants were detected in 75-82% of patients in 2 studies, and for VWF:Ag between 0.30-0.50 IU/mL, VWF sequence variants were detected in 44-60% of patients in 3 studies. A sensitivity of 0.90 (95% CI: 0.83 to 0.94), and a specificity of 0.91 (95% CI: 0.76 to 0.97) were observed for a platelet-dependent VWF activity /VWF:Ag ratio of <0.7 in detecting type 2 VWD (moderate certainty in the test accuracy results). VWF antigen and platelet-dependent activity are continuous variables with an increase in bleeding risk with decreasing levels. This systematic review shows that using a VWF activity/VWF:Ag ratio of <0.7 versus lower cutoff levels in patients with an abnormal initial VWD screen is more accurate for the diagnosis of type 2 VWD.

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Maternal and neonatal bleeding complications in relation to peripartum management in women with Von Willebrand disease: A systematic review

Blood Reviews ◽

10.1016/j.blre.2019.100633 ◽

2020 ◽

Vol 39 ◽

pp. 100633 ◽

Cited By ~ 4

Author(s):

M.C. Punt ◽

M.L. Waning ◽

E.P. Mauser-Bunschoten ◽

M.J.H.A. Kruip ◽

J. Eikenboom ◽

...

Keyword(s):

Systematic Review ◽

Von Willebrand Disease ◽

Bleeding Complications ◽

Von Willebrand

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The Presence of Periodontitis in Patients with Von Willebrand Disease: A Systematic Review

Applied Sciences ◽

10.3390/app11146408 ◽

2021 ◽

Vol 11 (14) ◽

pp. 6408

Author(s):

Alexandru Mester ◽

Leonardo Mancini ◽

Enrico Marchetti ◽

Mihaela Baciut ◽

Simion Bran ◽

...

Keyword(s):

Systematic Review ◽

Assessment Tool ◽

Meta Analysis ◽

Von Willebrand Disease ◽

Pocket Depth ◽

Cross Sectional ◽

Bleeding On Probing ◽

Probing Pocket Depth ◽

Electronic Search ◽

Von Willebrand

The aim of this systematic review and meta-analysis was to analyze the available evidence on the assessment of periodontal disease in patients with von Willebrand disease (VWD). An electronic search in three databases (PubMed, Web of Science, and Scopus) was conducted by three independent reviewers to identify cross-sectional, cohort, and clinical trial studies. Studies considered eligible for this review were evaluated according to the quality and risk assessment tool proposed by the CLARITY Group at McMaster University. In order to analyze the possible correlation of VWD patients and periodontitis and their susceptibility to bleeding during the periodontal screening phase, periodontal parameters evaluated were probing pocket depth (PPD), bleeding on probing (BOP), gingival bleeding index (GBI), and periodontal inflamed surface area (PISA). After a screening of 562 articles, three articles were selected for the qualitative analysis. Within the limitation of our review, VWD patients are not more susceptible to periodontitis as compared with non-VWD patients. Nevertheless, bleeding on probing and gingival index needs to be carefully taken into consideration during periodontal screening of VWD due to the possible presence of false positives.

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Postpartum Hemorrhage in Patients with Type 1 von Willebrand Disease: A Systematic Review

Seminars in Thrombosis and Hemostasis ◽

10.1055/s-0041-1736572 ◽

2021 ◽

Author(s):

Rebecca A.M. Pierce-Williams ◽

Mona M. Makhamreh ◽

Sophia Blakey-Cheung ◽

Zimeng Gao ◽

Huda B. Al-Kouatly

Keyword(s):

Systematic Review ◽

Blood Loss ◽

Postpartum Hemorrhage ◽

Primary Outcome ◽

Signs And Symptoms ◽

Von Willebrand Disease ◽

Inclusion Criteria ◽

Increased Risk ◽

Von Willebrand

AbstractType 1 von Willebrand disease (VWD) is the most common subtype of VWD, comprising 75% of VWD patients. We provide a systematic review of type 1 VWD in pregnancy. Our objective was to evaluate the rate of postpartum hemorrhage (PPH) in patients with known type 1 VWD. The primary outcome was rate of PPH. Primary PPH was defined as a cumulative blood loss ≥1,000 mL, or blood loss accompanied by signs and symptoms of hypovolemia within 24 hours postpartum or requiring blood products. Secondary PPH was defined as significant bleeding 24 hours to 12 weeks postpartum. Relevant articles published in English pertaining to VWD and pregnancy were identified without any time or study limitations. Seven articles (n = 144 pregnancies) met inclusion criteria. The rate of primary PPH was 4/144 (2.8%). The secondary PPH rate was reported in four studies, and occurred in 7/48 pregnancies (14.6%), ranging from 2 to 19 days postpartum. In conclusion, according to this systematic review, the frequency of primary PPH in pregnancies with known type 1 VWD is 2.8%. This is similar to the overall PPH rates of 3% reported in the literature. Although the sample size was small, secondary PPH occurred in almost 15% of pregnancies, while in the overall obstetrical population this occurs in approximately 1% of cases. Patients with known type 1 VWD may not be at increased risk of primary PPH, though they appear to bear increased risk of secondary PPH.

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Clinical manifestations and complications of childbirth and replacement therapy in 385 Iranian patients with type 3 von Willebrand disease

British Journal of Haematology ◽

10.1046/j.1365-2141.2000.02507.x ◽

2000 ◽

Vol 111 (4) ◽

pp. 1236-1239 ◽

Cited By ~ 129

Author(s):

M. Lak ◽

F. Peyvandi ◽

P. M. Mannucci

Keyword(s):

Replacement Therapy ◽

Clinical Manifestations ◽

Von Willebrand Disease ◽

Type 3 ◽

Von Willebrand ◽

Iranian Patients

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Morbidity and mortality of patients with haemophilia in Germany 2007/2008

Hämostaseologie ◽

10.1055/s-0037-1617208 ◽

2009 ◽

Vol 29 (S 01) ◽

pp. S7-S12

Author(s):

M. Spannagl ◽

W. Schramm ◽

H. Krebs ◽

Keyword(s):

Causes Of Death ◽

Severity Of Illness ◽

Von Willebrand Disease ◽

Morbidity And Mortality ◽

Haemophilia A ◽

Hiv Status ◽

Von Willebrand ◽

Existing Data

SummarySince 1978 an annual multicentric survey regarding the epidemiology of patients suffering of haemophilia is performed with support of haemophilia treating centres of any size. Again the actual compilation is resting upon a broad database returning to over 30 years of inquiry well representing both the actual and retrospective status of mortality. Prompted was exclusively information about patients with haemophilia A, B and von Willebrand disease. In particular anonymous data concerning the last 12 months about number of treated patients, type and severity of illness, HIV-status and detailed information about causes of death was inquired. This data was merged with existing data and analyzed statistically. In the 2007/2008 survey, a total

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Platelet Activation and Aggregation Induced by Recombinant von Willebrand Factors Reproducing Four Type 2B von Willebrand Disease Missense Mutations

Thrombosis and Haemostasis ◽

10.1055/s-0037-1614241 ◽

1998 ◽

Vol 79 (01) ◽

pp. 211-216 ◽

Cited By ~ 13

Author(s):

Lysiane Hilbert ◽

Claudine Mazurier ◽

Christophe de Romeuf

Keyword(s):

Platelet Aggregation ◽

Platelet Activation ◽

Von Willebrand Disease ◽

Platelet Glycoprotein ◽

Missense Mutations ◽

Inhibit Platelet Aggregation ◽

Wild Type ◽

A1 Domain ◽

Von Willebrand ◽

Willebrand Factor

SummaryType 2B of von Willebrand disease (vWD) refers to qualitative variants with increased affinity of von Willebrand factor (vWF) for platelet glycoprotein Ib (GPIb). All the mutations responsible for type 2B vWD have been located in the A1 domain of vWF. In this study, various recombinant von Willebrand factors (rvWF) reproducing four type 2B vWD missense mutations were compared to wild-type rvWF (WT-rvWF) for their spontaneous binding to platelets and their capacity to induce platelet activation and aggregation. Our data show that the multimeric pattern of each mutated rvWF is similar to that of WT-rvWF but the extent of spontaneous binding and the capacity to induce platelet activation and aggregation are more important for the R543Q and V553M mutations than for the L697V and A698V mutations. Both the binding of mutated rvWFs to platelets and platelet aggregation induced by type 2B rvWFs are inhibited by monoclonal anti-GPIb and anti-vWF antibodies, inhibitors of vWF binding to platelets in the presence of ristocetin, as well as by aurin tricarboxylic acid. On the other hand, EDTA and a monoclonal antibody directed against GPIIb/IIIa only inhibit platelet aggregation. Furthermore, the incubation of type 2B rvWFs with platelets, under stirring conditions, results in the decrease in high molecular weight vWF multimers in solution, the extent of which appears correlated with that of plasma vWF from type 2B vWD patients harboring the corresponding missense mutation. This study supports that the binding of different mutated type 2B vWFs onto platelet GPIb induces various degrees of platelet activation and aggregation and thus suggests that the phenotypic heterogeneity of type 2B vWD may be related to the nature and/or location of the causative point mutation.

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