Materiały źródłowe

• #1 Laboratory diagnosis of von Willebrand disease

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5600156/

  Von Willebrand disease (VWD) is considered the most common inherited bleeding disorder and may also be the most difficult to diagnose. […] Laboratory diagnosis requires a series of assays of von Willebrand factor (VWF) quantity and function, and factor VIII activity, with no single straightforward diagnostic test available to either confirm or exclude the diagnosis. […] Initial evaluation for VWD requires a combination of screening tests, as no single test can confirm the presence of fully functional VWF. […] An algorithm for VWD diagnosis is presented in Figure 1. […] A decreased VWF:RCo/VWF:Ag ratio should trigger evaluation of VWF multimer distribution, as a normal multimer distribution would lead to a diagnosis of type 2M and a loss of high molecular weight multimers would signal the presence of either type 2A or type 2B VWD.

• #1 Von Willebrand disease – Diagnosis & treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/von-willebrand-disease/diagnosis-treatment/drc-20354984

  Mild forms of von Willebrand disease can be difficult to diagnose because bleeding is common, and, for most people, doesn’t indicate a disease. However, if your doctor suspects you have a bleeding disorder, he or she might refer you to a blood disorders specialist (hematologist). […] To evaluate you for von Willebrand disease, your doctor will likely ask you detailed questions about your medical history and check for bruises or other signs of recent bleeding. […] Your doctor will also likely recommend the following blood tests: […] Von Willebrand factor antigen. This determines the level of von Willebrand factor in your blood by measuring a particular protein. […] Von Willebrand factor activity. There are a variety of tests to measure how well the von Willebrand factor works in your clotting process.

• #1 Diagnosis and Treatment of von Willebrand Disease and Rare Bleeding Disorders

  https://www.mdpi.com/2077-0383/6/4/45

  A bleeding history can be suggestive for VWD when at least three different haemorrhagic symptoms are reported or the bleeding score is greater than 3 in males or greater than 5 in females. […] The bleeding score (BS) is a summative index accounting for both the number and the severity of bleeding that is generated by summing the severity of all reported bleeding symptoms and graded according to an arbitrary scale. […] The diagnosis of VWD is based on different diagnostic assays, which evaluate the pleiotropic function of VWF and are summarized in Table 2, according the VWF Scientific and Standardization Subcommitte of the ISTH. […] VWF levels below 30 U/dL have been shown to be strongly associated with a significant clinical severity and the presence of the mutations in VWF gene.

• #1 The Diagnosis, Evaluation and Management of von Willebrand Disease: Full Report | NHLBI, NIH

  https://www.nhlbi.nih.gov/health-topics/diagnosis-evaluation-and-management-of-von-willebrand-disease/von-willebrand-disease-full-report

  The clinical evaluation of bleeding symptoms is a challenge, because mild bleeding symptoms are also very common in healthy populations. […] The initial step in assessment should focus on key aspects of the person’s clinical history to determine whether the person may benefit from further diagnostic evaluation. […] The initial laboratory evaluation for the etiology of a bleeding disorder should include a complete blood count (CBC including platelet count), prothrombin time (PT), activated partial thromboplastin time (PTT), and optionally either thrombin time or fibrinogen level. […] If the mucocutaneous bleeding history is strong, consider performing initial VWD assays (VWF:Ag, VWF:RCo, and FVIII) at the first visit. […] Initial tests for diagnosing or excluding VWD include the following three tests: VWF:RCo, VWF:Ag, and FVIII activity.

• #1 Diagnosis and Management of Von Willebrand Disease: Guidelines for Primary Care | AAFP

  https://www.aafp.org/pubs/afp/issues/2009/1201/p1261.html

  The initial step in the evaluation should focus on key aspects of the patient and family history. […] No simple, single laboratory test is available to screen for VWD, and the diagnosis is made using several specific laboratory tests. […] An isolated prolonged partial thromboplastin time or a normal partial thromboplastin time, prothrombin time, platelet count, and fibrinogen level in the presence of signs or symptoms of bleeding suggest the need for VWD-specific testing. […] Classification of subtypes is based on initial VWD testing and other specialized VWD tests, combined with the clinical history. […] Diagnosing type 1 VWD and distinguishing it from a low VWF level without VWD can be challenging, especially when VWF levels are only mildly decreased (30 to 50 IU per dL). Therefore, it is important to correlate severity and cause of bleeding with results of laboratory testing.

• #1 Von Willebrand disease – Diagnosis & treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/von-willebrand-disease/diagnosis-treatment/drc-20354984

  Factor VIII clotting activity. This shows whether you have abnormally low levels and activity of factor VIII. […] Von Willebrand factor multimers. This evaluates the structure of von Willebrand factor in your blood, its protein complexes and how its molecules break down. This information helps identify the type of von Willebrand disease you have. […] The results of these tests can fluctuate in the same person over time due to factors such as stress, exercise, infection, pregnancy and medications. So you might need to repeat some tests. […] If you have von Willebrand disease, your doctor might suggest that family members undergo tests to determine if this condition runs in your family.

• #1 Diagnosing Von Willebrand Disease | AAFP

  https://www.aafp.org/pubs/afp/issues/2010/0615/p1415.html

  According to the United Kingdom Haemophilia Centre Doctors’ Organisation (UKHCDO), there are no absolute recommendations for diagnosing vWD based on available evidence. […] Because of daily fluctuations in vWF antigen levels, the UKHCDO recommends testing patients on two separate occasions. […] According to the American Society of Hematology (ASH), a definitive diagnosis of vWD may be made if vWF antigen levels are less than 30 IU per dL. […] The ASH also describes a gray zone of 30 to 50 IU per dL, which is designated as low vWF.

• #1 Clinical presentation and diagnosis of von Willebrand disease – UpToDate

  https://www.uptodate.com/contents/clinical-presentation-and-diagnosis-of-von-willebrand-disease

  Clinical presentation and diagnosis of von Willebrand disease […] Diagnosis can be challenging; some individuals with low von Willebrand factor (VWF) levels may not actually have VWD (or any bleeding disorder), whereas others who have never had a bleeding challenge or never been tested have a significant bleeding risk from VWD that would benefit from evaluation and counseling. […] This topic reviews the clinical presentation, diagnosis, and differential diagnosis of VWD. […] VWD initial testing […] VWF antigen […] Platelet-dependent VWF activity (VWF:RCo or VWF:GPIbM) […] Factor VIII activity […] Other tests […] Repeat testing in individuals with borderline or discordant clinical and laboratory findings […] Additional testing to characterize (classify) the type of VWD […] VWF multimer analysis […] Ristocetin-induced platelet aggregation (RIPA) […] VWF binding to factor VIII (VWF:FVIIIB) […] Response to DDAVP […] Specialized tests for VWD […] Genetic testing […] Diagnostic confirmation.

• #1 Laboratory diagnosis of von Willebrand disease

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5600156/

  Diagnosis of type 1 VWD is made when the VWF: Ag and VWF:RCo are decreased, but in proportion to each other (VWF:RCo/VWF:Ag ratio 0.6.) […] Diagnosis of type 3 VWD is generally straightforward as the VWF:Ag and VWF:RCo will be clearly decreased. […] Diagnosis of type 2A VWD can also confirm the diagnosis, although novel sequence variants should be interpreted with caution. […] Diagnosis of a type 2B variant is confirmed by demonstration of increased platelet binding through either increased VWF:PB or increased LD-RIPA and must be discriminated from platelet-type VWD. […] Patients with an isolated decrease in FVIII should receive evaluation to exclude type 2N VWD, as this can easily be misdiagnosed as mild hemophilia A. […] Laboratory evaluation of VWD requires careful correlation of test results and clinical history.

• #1 von Willebrand Disease Workup: Approach Considerations, Evaluation of vWF Level and Function, Bleeding Time, PT, and aPTT

  https://emedicine.medscape.com/article/206996-workup

  This is a recessive disorder in which vWF protein is virtually undetectable. […] Guidelines from the National Institutes of Health and the United Kingdom recommend that the term „low vWF” rather than vWD be used to designate patients with an appropriate bleeding history and RCoF/vWF:Ag levels of 30-50 IU/dL. […] A laboratory evaluation of a patient’s response to administrations of desmopressin (DDAVP) is commonly performed to assess whether or not a patient can receive this product either therapeutically or prophylactically before surgery.

• #1 Von Willebrand Disease – VWD | Choose the Right Test

  https://arupconsult.com/content/von-willebrand-disease

  For that reason, repeat testing on a new plasma sample collected at a different time may be necessary for conclusive results. […] Genetic testing is typically not part of the initial workup for von Willebrand disease (VWD), but can be useful for phenotype confirmation, to help distinguish subtypes with similar phenotypes, and in the evaluation of family members of individuals who have known variants. […] Von Willebrand disease (VWD) assays, specifically von Willebrand factor ristocetin cofactor (VWF:RCo) activity (or another activity assay) and factor VIII (FVIII) activity, are recommended for monitoring patients with VWD who are being treated with medications such as desmopressin or VWF concentrates. […] Laboratory testing for VWD is appropriate in the following circumstances: Diagnosis of VWD in individuals with a personal history and physical examination that suggest a mucocutaneous bleeding disorder, particularly those with epistaxis, bleeding of gums, menorrhagia, or excessive mucosal bleeding after surgery.

• #1 VWACT – Overview: von Willebrand Factor Activity, Plasma

  https://www.mayocliniclabs.com/test-catalog/Overview/602170

  The VWF activity may be decreased in congenital VWD or AVWS that may be associated with are variety of disorders including monoclonal gammopathies, lymphoproliferative disorders, autoimmune disorders, hypothyroidism, severe aortic stenosis, left ventricular assist device, and arteriovenous malformation. […] The VWF activity may be increased in association with pregnancy or estrogen use (including oral contraceptives), acute (acute-phase reactant) or chronic inflammation, exercise or stress, liver disease, vasculitis, and thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS). Such increases in VWF activity may obscure the laboratory diagnosis of mild VWD.

• #1 von Willebrand Disease Workup: Approach Considerations, Evaluation of vWF Level and Function, Bleeding Time, PT, and aPTT

  https://emedicine.medscape.com/article/206996-workup

  Repeating tests at intervals of more than 2 weeks is advisable to confirm or definitively exclude the diagnosis of vWD. […] Screening tests typically include the following: Prothrombin time (PT), Activated partial thromboplastin time (aPTT), Factor VIII (FVIII) coagulant activity, Ristocetin cofactor (RCoF) activity, Concentration of vWF antigen (vWF:Ag). […] Additional testing to confirm the specific subtype may include the following: VWF collagen-binding activity, Low-dose ristocetin vWF-platelet binding, FVIII-VWF binding, VWF multimer analysis, VWF propeptide antigen. […] Genetic analysis can aid diagnosis of vWD type. […] Newer techniques, such as next-generation sequencing, have the capacity to analyze several genes simultaneously when necessary and to identify exon deletions and duplications, which makes it possible to identify causative vWF defects in more patients than previously.

• #1 The Diagnosis, Evaluation and Management of von Willebrand Disease: Full Report | NHLBI, NIH

  https://www.nhlbi.nih.gov/health-topics/diagnosis-evaluation-and-management-of-von-willebrand-disease/von-willebrand-disease-full-report

  Von Willebrand disease (VWD) is an inherited bleeding disorder that is caused by deficiency or dysfunction of von Willebrand factor (VWF), a plasma protein that mediates the initial adhesion of platelets at sites of vascular injury and also binds and stabilizes blood clotting factor VIII (FVIII) in the circulation. […] Guidelines for VWD diagnosis and management, based on the evidence from published studies and/or the opinions of experts, have been published for practitioners in Canada, Italy, and the United Kingdom, but not in the United States. […] The evaluation of a person for possible VWD or other bleeding disorders may be initiated because of a variety of clinical indications. […] The initial clinical assessment of a person who is being evaluated for VWD should focus on a personal history of excessive bleeding throughout the person’s life and any family history of a bleeding disorder.

• #1 Von Willebrand Disease in Women | ACOG

  https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2013/12/von-willebrand-disease-in-women

  Von Willebrand disease and other inherited and acquired disorders of coagulation and hemostasis should be considered in the differential diagnosis of all patients being evaluated for heavy menstrual bleeding, regardless of age. […] Because of the prevalence of von Willebrand disease as well as other inherited and acquired disorders of coagulation and hemostasis in women who seek evaluation for heavy menstrual bleeding, these conditions should be considered in the differential diagnosis of all women who are evaluated for heavy menstrual bleeding, regardless of age. […] The first step in the evaluation of women with suspected bleeding disorders involves obtaining a detailed medical history and performing a physical examination. […] In patients with a positive screening history, laboratory testing is indicated.

• #1

  https://haematologica.org/article/view/6652

  The diagnosis of VWD is then based on the presence of reduced VWF:RCo (or VWF:CB) (40 U/dL), with a further characterization of VWD type based on assessment of VWF:Ag, FVIII and multimer pattern. In general, VWF levels below 30 U/dL have been shown to be strongly associated with a significant clinical severity as assessed by a bleeding score and the presence of mutations in the VWF gene. […] Pediatric cases should be evaluated by using less stringent criteria. Mucocutaneous bleeding symptoms (e.g. epistaxis and bruising) are common in childhood and are not necessarily caused by a congenital bleeding disorder. […] A recent study that used the same bleeding questionnaire adopted for adults showed that with minimal modifications it is useful also in a pediatric setting, with a threshold score for a significant bleeding history of 2 or over.

• #1 von Willebrand disease

  https://www.rcpa.edu.au/Manuals/RCPA-Manual/Clinical-Presentations-and-Diagnoses/V/von-Willebrand-disease

  VWD is the most common inherited bleeding disorder. The diagnosis is usually considered because of a personal and/or family history of easy bruising or bleeding. Normal results on initial testing (Full blood count, APTT) do not exclude VWD. […] The diagnosis is established on the basis of assays of Factor VIII, von Willebrand factor Ag, Collagen binding assay, von Willebrand factor activity and possibly other assays. […] In females, blood should be collected during menstruation, normal results mid-cycle or during pregnancy do not exclude the diagnosis. […] Studies should be repeated on 2-4 occasions if clinical suspicion is high or if a previous diagnosis of VWD is to be refuted. […] If available, genetic testing could be considered.

• #1 Diagnosis of von Willebrand Disease in People With Type O Blood – Hematology & Oncology

  https://www.hematologyandoncology.net/archives/february-2014/diagnosis-of-von-willebrand-disease-in-people-with-type-o-blood/

  Diagnosis of von Willebrand Disease in People With Type O Blood […] The current standard screening evaluation of patients suspected to have VWD includes a measurement of VWF quantity (VWF antigen), VWF platelet binding (VWF ristocetin cofactor), VWF multimer pattern, and factor VIII. […] Therefore, in patients with a bleeding history consistent with VWD who have normal standard VWF assays, a VWF collagen binding defect should be considered. […] To mitigate some of this confusion, coagulation laboratories should use the same reference range to report VWF levels for those with blood type O as they would for anyone else in the population. […] After much debate, the expert panel decided to define VWD as a VWF level that is 30 IU/ dL (30% of normal) or lower. […] Clinical bleeding episodes that require treatment can occur in patients with low VWF even if they do not meet the strict criteria for the diagnosis of VWD.

• #1 Von Willebrand Disease (VWD) | Symptoms & Treatments | NBDF

  https://www.bleeding.org/bleeding-disorders-a-z/types/von-willebrand-disease

  A combination of blood tests are used to diagnose VWD, including a VWF antigen test, which measures the amount of VWF in the blood, tests that measure clotting time and ability to form a clot, and tests measuring platelet function. […] People with VWD usually have less than 50% of normal VWF in their blood. After a diagnosis of VWD is discovered, an additional is given to determine the type. […] The best place for patients with bleeding disorders to be diagnosed and treated is at one of the federally funded hemophilia treatment centers (HTCs) that are spread throughout the country. […] HTCs provide comprehensive care from skilled hematologists and other professional staff, including nurses, physical therapists, social workers and sometimes dentists, dieticians and other healthcare providers.

• #1 Von Willebrand Disease in Women | ACOG

  https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2013/12/von-willebrand-disease-in-women

  If a patient’s medical history is suggestive of an underlying bleeding condition, specific tests for von Willebrand disease may be indicated, including von Willebrand-ristocetin cofactor activity, vWF antigen, and factor VIII. […] Because existing laboratory assays have limitations and no single diagnostic test reliably identifies von Willebrand disease, it is recommended that these tests be performed and interpreted in conjunction with a hematologist. […] Once a diagnosis of von Willebrand disease has been established, a multidisciplinary approach to management, which involves obstetriciangynecologists and hematologists, results in optimal treatment outcomes. […] Collaboration with a hematologist is recommended to aid in the planning for gynecologic surgery and obstetric management.

• #1 The Diagnosis, Evaluation and Management of von Willebrand Disease: Full Report | NHLBI, NIH

  https://www.nhlbi.nih.gov/health-topics/diagnosis-evaluation-and-management-of-von-willebrand-disease/von-willebrand-disease-full-report

  In the adolescent or adult woman who does not desire pregnancy, but may desire future childbearing, the first choice of therapy for menorrhagia should be combined oral contraceptives. […] Women planning for pregnancy should have, before conception, an evaluation with a hematologist and a high-risk obstetrician, both of whom are skilled in the management of VWD. […] The diagnosis of VWD can be complex, and no single diagnostic approach is suitable for all patients.

• #1 Diagnosing Von Willebrand Disease | Hematology-Oncology Associates of CNY

  https://www.hoacny.com/patient-resources/blood-disorders/what-von-willebrand-disease/diagnosing-von-willebrand-disease

  Early diagnosis of von Willebrand disease (VWD) is important to make sure that you’re treated and can live a normal, active life. […] Sometimes VWD is hard to diagnose. People who have type 1 or type 2 VWD may not have major bleeding problems. Thus, they may not be diagnosed unless they have heavy bleeding after surgery or some other trauma. […] To find out whether you have VWD, your doctor will review your medical history and the results from a physical exam and tests. […] No single test can diagnose VWD. Your doctor may recommend one or more blood tests to diagnose the disorder. […] You may have these tests more than once to confirm a diagnosis. Your doctor also may refer you to a hematologist to confirm the diagnosis and for followup care. A hematologist is a doctor who specializes in diagnosing and treating blood disorders.

• #2 Diagnosis and Management of Von Willebrand Disease: Guidelines for Primary Care | AAFP

  https://www.aafp.org/pubs/afp/issues/2009/1201/p1261.html

  Von Willebrand disease is an inherited condition characterized by deficiency of von Willebrand factor, which is essential in hemostasis. The National Heart, Lung, and Blood Institute has released new evidence-based guidelines for the diagnosis and management of the disease. Diagnosis is usually made by reviewing the patient’s personal and family history of bleeding and by clinical evaluation for more common reasons for bleeding, supplemented with laboratory tests. […] Von Willebrand factor levels of 30 IU per dL or lower are required for the definite diagnosis of inherited von Willebrand disease. […] Evaluation for VWD (or other bleeding disorders) should be considered for the following patients: (1) currently asymptomatic patients undergoing a surgical or interventional procedure if personal or family history of bleeding is a concern; (2) patients with current symptoms or a history of increased bleeding, abnormal laboratory study results, or a family history of a bleeding disorder; and (3) patients with a previous VWD diagnosis, but no supporting laboratory documentation.

• #2 Diagnosing von Willebrand Disease | NYU Langone Health

  https://nyulangone.org/conditions/von-willebrand-disease-in-children/diagnosis

  Von Willebrand disease is the most common inherited bleeding disorder. […] Our specialists can make an accurate diagnosis, even in children with the mildest form of von Willebrand disease. […] Specialists at Hassenfeld Childrens Hospital at NYU Langone are experienced in making an accurate diagnosis, even in children with the mildest form of von Willebrand disease, whose symptoms may be missed by others. […] At Hassenfeld Childrens Hospital, diagnosing von Willebrand disease begins with a complete medical history. […] The doctor may perform a physical exam to look for signs of bruising or recent bleeding in the muscles and joints. […] Blood test results can determine if your child has von Willebrand disease and, if so, which type. […] It may take up to one week for your doctor to receive the blood test results.

• #2 Updated guidelines for the diagnosis of Von Willebrand disease – BJH

  https://www.bjh.be/updated-guidelines-for-the-diagnosis-of-von-willebrand-disease/

  Von Willebrand disease (VWD) is the most common hereditary bleeding disorder globally. […] Developed from systematic evidence reviews from the Outcomes and Implementation Research Unit at the University of Kansas Medical Center (KUMC), the American Society of Haematology (ASH), in collaboration with the National Haemophilia Foundation (NHF) and the World Federation of Haemophilia (WFH), have developed updated guidelines for the diagnosis of VWD. […] For patients with a low probability of VWD, a validated bleeding-assessment tool (BAT) is recommended as an initial screening tool to identify which patients required specific blood testing over non-standardised clinical assessment. Specific blood testing for VWD refers to VWF antigen (VWF:Ag), platelet-dependent VWF activity (eg, VWF glycoprotein IbM [VWF:GPIbM]), and factor VIII coagulant activity (FVIII:C).

• #2 Von Willebrand disease

  https://www.nhs.uk/conditions/von-willebrand-disease/

  Von Willebrand disease can be hard to diagnose because the symptoms are often mild. […] A GP may examine you to check symptoms such as bruising. […] If they think you could have von Willebrand disease, they’ll refer you to a specialist in blood conditions (haematologist). […] Von Willebrand disease is diagnosed using blood tests. You’ll need to have several blood tests over a few days or weeks. […] If tests show you have von Willebrand disease, the specialist will tell you which type you have. Types 1 and 2 are the most common and usually cause mild symptoms. Type 3 is rare and causes more severe symptoms. […] If you’re diagnosed with von Willebrand disease, your immediate family should also be offered tests as there’s a chance they could also have the condition.

• #2 Diagnosis and Management of Von Willebrand Disease: Guidelines for Primary Care | AAFP

  https://www.aafp.org/pubs/afp/issues/2009/1201/p1261.html

  The initial step in the evaluation should focus on key aspects of the patient and family history. […] No simple, single laboratory test is available to screen for VWD, and the diagnosis is made using several specific laboratory tests. […] An isolated prolonged partial thromboplastin time or a normal partial thromboplastin time, prothrombin time, platelet count, and fibrinogen level in the presence of signs or symptoms of bleeding suggest the need for VWD-specific testing. […] Classification of subtypes is based on initial VWD testing and other specialized VWD tests, combined with the clinical history. […] Diagnosing type 1 VWD and distinguishing it from a low VWF level without VWD can be challenging, especially when VWF levels are only mildly decreased (30 to 50 IU per dL). Therefore, it is important to correlate severity and cause of bleeding with results of laboratory testing.

• #2 Pediatric Von Willebrand Disease Workup: Laboratory Studies, Other Tests

  https://emedicine.medscape.com/article/959825-workup

  Screening tests for von Willebrand disease (VWD) include the following: Complete blood count (CBC), Prothrombin time (PT), Activated partial thromboplastin time (aPTT). […] Assess platelet number and morphology, which should be normal in most patients with von Willebrand disease, except those with type 2B von Willebrand disease, who may have thrombocytopenia. […] PT is within the reference range in von Willebrand disease. […] Approximately 25% of patients with type 1 von Willebrand disease have aPTT results outside of the reference range. […] Because aPTT is an insensitive test for von Willebrand disease, add von Willebrand factor (VWF) activity and von Willebrand factor antigen to the screening tests performed for patients with suspected bleeding disorders. […] Specific assays include the following: FVIII activity, von Willebrand factor activity (run as ristocetin cofactor activity in some labs), von Willebrand factor antigen, von Willebrand factor multimers.

• #2 von Willebrand disease

  https://www.rcpa.edu.au/Manuals/RCPA-Manual/Clinical-Presentations-and-Diagnoses/V/von-Willebrand-disease

  VWD is the most common inherited bleeding disorder. The diagnosis is usually considered because of a personal and/or family history of easy bruising or bleeding. Normal results on initial testing (Full blood count, APTT) do not exclude VWD. […] The diagnosis is established on the basis of assays of Factor VIII, von Willebrand factor Ag, Collagen binding assay, von Willebrand factor activity and possibly other assays. […] In females, blood should be collected during menstruation, normal results mid-cycle or during pregnancy do not exclude the diagnosis. […] Studies should be repeated on 2-4 occasions if clinical suspicion is high or if a previous diagnosis of VWD is to be refuted. […] If available, genetic testing could be considered.

• #2 Laboratory Diagnosis of von Willebrand Disease | American Society for Clinical Laboratory Science

  https://clsjournal.ascls.org/content/30/2/65

  At minimum, three tests are included in the current standard practice for laboratory diagnosis of VWD. These include (1) von Willebrand factor antigen level (VWF:Ag), (2) von Willebrand factor activity (VWF:Act or VWF:RCo) level, and (3) circulating level of FVIII (FVIII:C). […] The VWF:Ag is most often an immuno-based assay that can be performed as an ELISA (enzyme-linked immunosorbent assay) method or as an automated turbidimetric method using latex beads coated with antibody to VWF. […] Von Willebrand activity can be measured by a number of different methods including; 1) the ristocetin cofactor assay (VWF:RCo), the gold standard or reference method for measuring VWF activity; 2) automated immunoturbidimetric assays 3) a chemiluminescence assay; or 4) an enzyme-linked immunosorbent assays (ELISA); or 5) flow cytometry.

• #2 The Diagnosis, Evaluation and Management of von Willebrand Disease: Full Report | NHLBI, NIH

  https://www.nhlbi.nih.gov/health-topics/diagnosis-evaluation-and-management-of-von-willebrand-disease/von-willebrand-disease-full-report

  The clinical evaluation of bleeding symptoms is a challenge, because mild bleeding symptoms are also very common in healthy populations. […] The initial step in assessment should focus on key aspects of the person’s clinical history to determine whether the person may benefit from further diagnostic evaluation. […] The initial laboratory evaluation for the etiology of a bleeding disorder should include a complete blood count (CBC including platelet count), prothrombin time (PT), activated partial thromboplastin time (PTT), and optionally either thrombin time or fibrinogen level. […] If the mucocutaneous bleeding history is strong, consider performing initial VWD assays (VWF:Ag, VWF:RCo, and FVIII) at the first visit. […] Initial tests for diagnosing or excluding VWD include the following three tests: VWF:RCo, VWF:Ag, and FVIII activity.

• #2 von Willebrand Disease Workup: Approach Considerations, Evaluation of vWF Level and Function, Bleeding Time, PT, and aPTT

  https://emedicine.medscape.com/article/206996-workup

  Repeating tests at intervals of more than 2 weeks is advisable to confirm or definitively exclude the diagnosis of vWD. […] Screening tests typically include the following: Prothrombin time (PT), Activated partial thromboplastin time (aPTT), Factor VIII (FVIII) coagulant activity, Ristocetin cofactor (RCoF) activity, Concentration of vWF antigen (vWF:Ag). […] Additional testing to confirm the specific subtype may include the following: VWF collagen-binding activity, Low-dose ristocetin vWF-platelet binding, FVIII-VWF binding, VWF multimer analysis, VWF propeptide antigen. […] Genetic analysis can aid diagnosis of vWD type. […] Newer techniques, such as next-generation sequencing, have the capacity to analyze several genes simultaneously when necessary and to identify exon deletions and duplications, which makes it possible to identify causative vWF defects in more patients than previously.

• #2 Laboratory Diagnosis of von Willebrand Disease | American Society for Clinical Laboratory Science

  https://clsjournal.ascls.org/content/30/2/65

  VWF multimer analysis assesses the size distribution of VWF multimers and aids in differentiating subtypes of VWD. It consists of electrophoresis to separate the VWF multimers on an agarose gel. […] Additional assays can be used in VWD testing such as the VWD platelet-binding assay to differentiate between subtype 2B VWD and platelet-type VWD; and VWD FVIII binding assay to diagnose subtype 2N VWD. These assays would be performed in highly specialized laboratories.

• #2 von Willebrand disease: A guide for the internist | Cleveland Clinic Journal of Medicine

  https://www.ccjm.org/content/91/2/119

  This is a qualitative assessment of the size distribution of VWF multimers in plasma, which helps distinguish the patients subtype of VWD. […] The factor VIII coagulant assay is typically used in patients with a substantial bleeding history that is suspicious for hemophilia. […] This is an enzyme-linked immunoassay that evaluates the ability of VWF to bind recombinant factor VIII. […] Desmopressin promotes excretion of stored VWF from endothelial cells into plasma. […] Genotyping is not required to diagnose VWD and is done only in select clinical scenarios.

• #2 Updated guidelines for the diagnosis of Von Willebrand disease – BJH

  https://www.bjh.be/updated-guidelines-for-the-diagnosis-of-von-willebrand-disease/

  Newer assays, that measure the platelet-binding activity of VWF, for e.g VWF:GPIbM, VWF:GPIbR, should be used over the VWF ristocetin cofactor assay (VWF:RCo) for the diagnosis of VWD. […] A VWF levels of 0.30 IU/mL regardless of bleeding symptoms, and a VWF of 0.50 IU/mL with abnormal bleeding, should be used to confirm a diagnosis of type 1 VWD. […] For the diagnosis of type 1C VWD, a trial of desmopressin is suggested, with 1- and 4-hour post-infusion blood work to confirm increased VWF clearance, as opposed to VWF propeptide (VWFpp)/VWF:Ag testing. […] When type 2 VWD is suspected, it is suggested that a platelet-dependent VWF activity/VWF:Ag ratio 0.7 be used as a cut-off, rather than 0.5, for patients with an abnormal initial VWD screen. […] It is also suggested that if additional testing is required for the diagnosis of type 2A, 2B or 2M VWD, that VWF multimer analysis or VWF collagen binding (VWF:CB)/VWF:Ag (the ratio of VWF collagen binding to antigen) be used.

• #2 von Willebrand Disease Workup: Approach Considerations, Evaluation of vWF Level and Function, Bleeding Time, PT, and aPTT

  https://emedicine.medscape.com/article/206996-workup

  In a patient whose personal and family history raises suspicion for von Willebrand disease (vWD), the basic diagnosis of vWD involves measurement of plasma von Willebrand factor (vWF) antigen levels and its platelet-dependent activity. […] Currently, many hemostasis laboratories offer these tests. However, the differentiation of vWD as type 1, 2A, 2B, 2M, 2N or 3 must be done through a specialized laboratory that routinely performs specific tests such as multimer analysis or ristocetin-induced platelet agglutination. […] Initial laboratory studies are directed towards documenting a deficiency of von Willebrand factor (vWF). […] Levels of vWF vary with physiologic stress; in particular, plasma levels increase with estrogens, vasopressin, growth hormone, and adrenergic stimuli. Thus, vWF levels may intermittently be normal in patients with von Willebrand disease (vWD), and measurements should be repeated to confirm abnormal results.

• #2 Diagnosing von Willebrand Disorder | The Haemophilia Society

  https://haemophilia.org.uk/bleeding-disorders/von-willebrand-disease/diagnosing-von-willebrand-disease/

  No single test can diagnose VWD. Diagnostic testing to confirm VWD may have to be repeated because levels of VWF fluctuate and having these tests more than once to confirm or exclude a diagnosis is vital. […] Your medical team will collect a blood sample to send to a laboratory for testing. Due to the specialised nature of these tests, it may take up to two or three weeks to get your results.

• #2 Diagnosis and management of von Willebrand disease in Australia – Favaloro – Annals of Blood

  https://aob.amegroups.org/article/view/4450/5193

  Von Willebrand disease (VWD) is reportedly the most common inherited bleeding disorder, and can also arise as an acquired event where it is termed von Willebrand syndrome. […] Diagnosis requires evidence of personal or family history of (mainly) mucocutaneous bleeding, together with laboratory findings that demonstrate quantitative or qualitative defects in VWF. […] Current classification of VWD, based on whether VWF quantitative deficiencies (VWD types 1 and 3), or qualitative defects (type 2 VWD) are present, defines 6 types. […] Type 1 VWD is characterized by quantitative deficiency of an otherwise functionally normal VWF. Type 1 VWD is therefore confirmed by detection of reduced levels of VWF protein (antigen; VWF:Ag), and similar proportionally decreased levels of functional VWF, which can be identified by various assays, including VWF ristocetin cofactor (VWF:RCo) and collagen binding (VWF:CB).

• #2 Von Willebrand Disease – Hematology and Oncology – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/hematology-and-oncology/thrombocytopenia-and-platelet-dysfunction/von-willebrand-disease

  Von Willebrand disease is suspected in patients with unexplained bleeding, particularly those with a family history of a similar bleeding diathesis. […] Diagnosis requires measuring total plasma VWF antigen, VWF function as determined by the ability of plasma to support agglutination of normal platelets by ristocetin (ristocetin cofactor activity), and the plasma factor VIII level. […] Type 2 subtypes are suspected if test results are discordant, ie, VWF antigen is higher than expected for the degree of abnormality in ristocetin cofactor activity. […] Diagnosis is confirmed by demonstrating a reduced concentration of large VWF multimers on agarose gel electrophoresis. […] Patients with type 3 VWD have no detectable VWF and a marked deficiency of factor VIII.

• #2 Diagnosis and management of von Willebrand disease in Australia – Favaloro – Annals of Blood

  https://aob.amegroups.org/article/view/4450/5193

  Type 2 VWD patients exhibit qualitative VWF defects; accordingly, levels of VWF protein (VWF:Ag) might be normal (although it is usually reduced), FVIII levels might also be normal or low, but most importantly, VWF function is somehow impaired. […] The current review essentially updates a previous analogous review published in 2011. Our own approach to diagnosis/exclusion of VWD is represented in algorithmic form. […] For all patients we recommend a minimum four test (basic) panel of investigations, and namely FVIII, VWF:Ag, VWF:CB and a GPIb binding assaybe it classical VWF:RCo or one of the modern alternatives. […] Based on national statistics and a locally maintained database, the breakdown of VWD types is as shown in Tables 3,4. […] In line with the United Kingdom Haemophilia Centre Doctors Organization guideline, we believe that diagnosis of VWD requires a minimum four test panel covering FVIII, VWF:Ag, GPIb binding (e.g., VWF:RCo or VWF:GPIbM), and collagen binding (VWF:CB).

• #2 von Willebrand disease: A guide for the internist | Cleveland Clinic Journal of Medicine

  https://www.ccjm.org/content/91/2/119

  Specialized tests for VWD require complex assays, and many preanalytic variables can affect their precision and accuracy, including patient age, sex, race, blood group, and comorbid conditions such as recent bleeding, infection, hepatic dysfunction, inflammatory conditions, and renal disease. […] The next step is to measure the concentration of VWF protein (antigen) with an immunologic assay, most commonly an enzyme-linked immunosorbent assay or latex-enhanced immunoassay. […] This test evaluates platelet-dependent VWF activity by assessing the ability of VWF to bind platelet glycoprotein Ib in the presence of the antibiotic ristocetin. […] The VWF activity assay is a functional test that uses either the ristocetin cofactor assay or a monoclonal antibody that targets the region of the VWF molecule that binds to the glycoprotein Ib receptor as a measure of VWF activity.

• #2 Facts About von Willebrand disease (VWD) – VONVENDI®

  https://www.vonvendi.com/facts-about-vwd

  How is VWD diagnosed In most cases, diagnosing VWD involves reviewing your personal history of abnormal bleeding or bruising, along with screening and diagnostic tests. These tests show your healthcare provider the amount of clotting proteins (VWF and FVIII) in your blood and if those proteins are functioning properly or not. […] Even though it’s the most common inherited bleeding disorder, many people with VWD face a long road to diagnosis. In one survey of women with VWD, there was an average of 16 years (range 0-39) between the first symptoms and diagnosis of a bleeding disorder. […] An accurate diagnosis is extremely important for women in order to avoid unnecessary and/or invasive treatments, such as hysterectomy.

• #2 Pediatric Von Willebrand Disease Workup: Laboratory Studies, Other Tests

  https://emedicine.medscape.com/article/959825-workup

  As previously stated, testing on multiple occasions may be needed to confirm the diagnosis of von Willebrand disease, given the influence of estrogen, stress, and inflammation on von Willebrand factor levels. […] In some laboratories, platelet von Willebrand factor analysis is performed. Gene analysis can also be performed for diagnosis.

• #2 Von Willebrand Disease in Women | ACOG

  https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2013/12/von-willebrand-disease-in-women

  Von Willebrand disease and other inherited and acquired disorders of coagulation and hemostasis should be considered in the differential diagnosis of all patients being evaluated for heavy menstrual bleeding, regardless of age. […] Because of the prevalence of von Willebrand disease as well as other inherited and acquired disorders of coagulation and hemostasis in women who seek evaluation for heavy menstrual bleeding, these conditions should be considered in the differential diagnosis of all women who are evaluated for heavy menstrual bleeding, regardless of age. […] The first step in the evaluation of women with suspected bleeding disorders involves obtaining a detailed medical history and performing a physical examination. […] In patients with a positive screening history, laboratory testing is indicated.

• #2 Diagnosis of von Willebrand disease | Hemophilia

  https://www.hemophilia.ca/diagnosis-of-von-willebrand-disease/

  No, diagnosing VWD is not easy. Many doctors are not familiar with it. As a result, VWD is often misdiagnosed. […] For this reason, a person who thinks he/she has a bleeding problem should see a hematologist who specializes in bleeding disorders. Such a doctor can be found at a bleeding disorder treatment centre. There, a diagnosis will be made by a specialist who is familiar with bleeding disorders and who has experience doing the proper blood tests. […] Diagnosing VWD is difficult even for an experienced doctor. This is because the results of a person’s blood tests can vary from day to day. The test results can be normal, even when the person has VWD. […] No, they are not. Routine blood tests will often give normal results in people who have von Willebrand disease. […] A doctor who suspects VWD will first take a complete family history. He/she will then do a number of blood tests to find out: if the person has VWD and what type of VWD the person has.

• #3 How is von Willebrand disease diagnosed?Dr. Jürgen Patzke

  https://www.siemens-healthineers.com/en-us/hemostasis/innovance-assays/innovance-vwf-ac-assay/von-willebrand-disease

  Recommended by the ASH ISTH NHF WFH 2021 guidelines on the diagnosis of von Willebrand disease as first line assays are VWF:RCo, VWF:GPIbM or VWF:GPIbR. […] In the ASH ISTH NHF WFH 2021 guidelines on the diagnosis of von Willebrand disease, the panel suggests newer assays to measure VWF platelet-binding activity (e.g., VWF:GPIbM, VWF:GPIbR) rather than VWF:RCo due to their: Lower coefficient of variation and higher reproducibility compared to VWF:RCo, Concern that D1472H sequence variant may lead to overdiagnosis of VWD by the VWF:RCo method.

• #3 Diagnosis of von Willebrand Disease in People With Type O Blood – Hematology & Oncology

  https://www.hematologyandoncology.net/archives/february-2014/diagnosis-of-von-willebrand-disease-in-people-with-type-o-blood/

  Diagnosis of von Willebrand Disease in People With Type O Blood […] The current standard screening evaluation of patients suspected to have VWD includes a measurement of VWF quantity (VWF antigen), VWF platelet binding (VWF ristocetin cofactor), VWF multimer pattern, and factor VIII. […] Therefore, in patients with a bleeding history consistent with VWD who have normal standard VWF assays, a VWF collagen binding defect should be considered. […] To mitigate some of this confusion, coagulation laboratories should use the same reference range to report VWF levels for those with blood type O as they would for anyone else in the population. […] After much debate, the expert panel decided to define VWD as a VWF level that is 30 IU/ dL (30% of normal) or lower. […] Clinical bleeding episodes that require treatment can occur in patients with low VWF even if they do not meet the strict criteria for the diagnosis of VWD.

• #3 VWACT – Overview: von Willebrand Factor Activity, Plasma

  https://www.mayocliniclabs.com/test-catalog/Overview/602170

  The VWF activity may be decreased in congenital VWD or AVWS that may be associated with are variety of disorders including monoclonal gammopathies, lymphoproliferative disorders, autoimmune disorders, hypothyroidism, severe aortic stenosis, left ventricular assist device, and arteriovenous malformation. […] The VWF activity may be increased in association with pregnancy or estrogen use (including oral contraceptives), acute (acute-phase reactant) or chronic inflammation, exercise or stress, liver disease, vasculitis, and thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS). Such increases in VWF activity may obscure the laboratory diagnosis of mild VWD.

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