scholarly journals Von Willebrand Factor (VWF) Propeptide and Factor VIII (FVIII) Levels Identify the Contribution of Decreased Synthesis and/or Increased Clearance Mechanisms in the Pathogenesis of Type 1 Von Willebrand Disease (VWD) in the Zimmerman Program

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 874-874
Author(s):  
Sandra L Haberichter ◽  
Pamela A Christopherson ◽  
Veronica H Flood ◽  
Joan Cox Gill ◽  
Kenneth D Friedman ◽  
...  
Keyword(s):  
Underlying Mechanism ◽  
Laboratory Diagnosis ◽  
Von Willebrand Disease ◽  
Sequence Variant ◽  
Specific Marker ◽  
Common Precursor ◽  
True Type ◽  
The Mean ◽  
Von Willebrand

Abstract Laboratory diagnosis of VWD is challenging, with multiple tests required to obtain an accurate assessment. Plasma VWF level represents a balance between synthesis, secretion, and clearance. Although synthesized together, VWFpp and VWF circulate in plasma independently with differing half-lives. Plasma VWFpp level is used to assess synthesis/secretion, VWFpp/VWF:Ag ratio to indicate clearance of VWF, and FVIII/VWF:Ag ratio to assess VWF synthesis and clearance. We sought to identify the underlying VWD pathophysiology in subjects enrolled in the Zimmerman Program including 245 healthy controls, 175 "low VWF" (VWF:Ag 30-50), 69 type 1 (VWF:Ag<30), 57 type 1C (VWF:Ag<30 and VWFpp/VWF:Ag>3), and 9 type 1-severe (1S) (VWF:Ag<5). FVIII levels were significantly reduced (p < 0.0001) in VWD subjects compared to controls. The mean FVIII/VWF:Ag ratio in "low VWF" (1.5), types 1 (2.4), 1C (2.9), and 1S (8.7) were significantly different from controls (p < 0.0001). VWFpp levels in all subjects were significantly lower than controls with type 1S subjects demonstrating the most reduced levels. The mean VWFpp/VWF:Ag was significantly increased compared to controls in type 1 (1.9) and 1C (8.4) subjects. VWFpp level, VWFpp/VWF:Ag and FVIII/VWF:Ag were used to define the underlying pathophysiology in VWD subtypes. A VWFpp/VWF:Ag > 3.0 indicates increased VWF clearance. VWFpp level < 50 IU/dL or FVIII/VWF:Ag > 2.0 indicate reduced VWF synthesis/secretion. A combination of increased clearance/reduced secretion may be identified or neither mechanism. Only 9% of "low VWF" subjects had increased FVIII/VWF:Ag, while 15% had decreased VWFpp suggesting reduced secretion. Other unidentified mechanisms may explain the majority of these "low VWF" cases. In type 1, 38 had increased FVIII/VWF:Ag and 48 had reduced VWFpp indicating reduced secretion in 55-70% of cases. In type 1C, all had increased VWFpp/VWF:Ag, 44 had increased FVIII/VWF:Ag and 19 reduced VWFpp. Reduced secretion may play a role in 33 -77% of these subjects, in addition to increased VWF clearance. All 9 type 1S had reduced VWFpp and 8/9 had increased FVIII/VWF, indicating a reduced secretion mechanism in nearly all cases. To assess the influence of sequence variant (SV) location on VWF synthesis/secretion, levels were analyzed by presence or absence of SV and SV location by VWF domain. 62% of the VWD cohort had SV identified (23% with >1 SV) while 38% had no SV. Of those with SV, 52% had increased FVIII/VWF:Ag and 48% had decreased VWFpp, suggesting reduced secretion; 31% had increased VWFpp/VWF:Ag indicative of increased clearance; and 32% had neither mechanism. In the group with no SV, only 7% had increased FVIII/VWF:Ag and 17% had decreased VWFpp while 77% had neither mechanism identified. Of those subjects with reduced secretion as indicated by increased FVIII/VWF:Ag, the majority of SV were found in A1 (29%), D3 (22%) and D1 (13%) which was similar to those with reduced secretion indicated by decreased VWFpp level in A1 (25%), D3 (21%) and D1 (15%). An increased VWFpp/VWF:Ag ratio predicting increased clearance was found in patients with SV in D3, A1 and D4 domains. Patients with both increased clearance and reduced secretion had SV in A1 (53%), D3 (19%) and D4 (11%). Subjects who had neither mechanism identified had SV in A2 (25%), C1-C6 (18%) and D2 (16%), suggesting these SV are associated with other, yet unidentified mechanisms. Although VWFpp level and FVIII/VWF:Ag are both thought to indicate VWF synthesis/secretion, some discrepancies were observed. VWFpp level may be the more specific marker, as VWFpp and VWF share a common precursor protein. Reduced secretion plays a role in nearly all type 1S, 70% of type 1, and 15% of "low VWF" subjects. Additionally, SV in A1, D3, and D4 may be associated with decreased secretion and/or increased clearance while those in D1 may be associated with decreased secretion alone. No SV were found in 85% of "low VWF" subjects that is consistent with the observation that the majority of these cases (81%) had neither decreased secretion nor increased clearance mechanisms identified. The mechanistic cause of bleeding in these patients remains undefined. Assay of VWFpp and corresponding VWF:Ag ratios may help to define the underlying mechanism in VWD subjects and identify true type 1C VWD patients, which is clinically important for therapeutic treatment. Disclosures Flood: CSL Behring: Consultancy; Baxalta: Consultancy. Friedman:Shire: Consultancy; NovoNordisk: Consultancy; CSL Behring: Consultancy; Alexion: Speakers Bureau.

The Power of a Standardized Bleeding Score in Diagnosing Pediatric Type 1 Von Willebrand Disease.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1293-1293
Author(s):  
Paul D Marcus ◽  
Kidan G Nire ◽  
Linda Grooms ◽  
Jennifer Klima ◽  
Sarah O'Brien
Keyword(s):  
Platelet Function ◽  
Predictive Value ◽  
Care Setting ◽  
Tertiary Care ◽  
Bleeding Disorder ◽  
Von Willebrand Disease ◽  
The Mean ◽  
Bleeding Score ◽  
Von Willebrand

Abstract Abstract 1293 Poster Board I-315 INTRODUCTION Type I von Willebrand disease (VWD) is the most common inherited bleeding disorder. Repetitive testing of von Willebrand factor (VWF) levels is necessary before the diagnosis can be safely ruled out, as VWF levels fluctuate in response to genetic and environmental factors. A predictive bleeding score (BS) could reveal individuals that may benefit from repetitive testing and those for whom repetitive testing is unlikely to be of benefit. While a standardized questionnaire (the Vicenza score) was developed to evaluate hemorrhagic symptoms, it was never prospectively validated for a pediatric population in a tertiary care setting. SUBJECTS The study targeted children, ages 0 to 17 years, referred to the Hemostasis and Thrombosis Center (HTC) of Nationwide Children's Hospital for a coagulation evaluation as a result of bleeding symptoms, family history of a bleeding disorder and/or abnormal coagulation labs found during pre-operative screening. Children were excluded if they had a previously diagnosed bleeding disorder, if their caregiver did not speak English or if the child did not undergo VWF:Ag and VWF:RCo testing. METHODS Prior to the diagnosis or exclusion of a bleeding disorder in the child, caregivers consented to answer the questionnaire over the telephone. Descriptions of the Vicenza score are available online (http://www.euvwd.group.shef.ac.uk/bleed_score.htm). LABORATORY TESTING A single VWF:Ag or VWF:RCo <30 IU/dL was classified as “Definite Type 1 VWD” while levels from 30-50 IU/dL were classified as “Low VWF” (http://www.nhlbi.nih.gov/guidelines/vwd). Platelet function analysis (PFA-100) screened for platelet function defects, with some patients undergoing follow-up platelet aggregation studies and/or platelet electron microscopy. Laboratory studies from other institutions were excluded from analysis. Patients' medical records were reviewed after hematologic evaluation, and the resultant data was analyzed with STATA 10.1 (Stata Corp., College Station, TX). RESULTS A total of 104 children (52 females and 52 males) with a mean age of 7.53 years (range 1 month to 17 years) were included. At least one hemorrhagic symptom was present in 99 of the 104 children (95%) with the mean number of symptoms being 2.87 (range 0 to 7). The mean Vicenza score was 3.24 (range -1 to 13). Of the 104 children, 8 met criteria for “Definite Type 1 VWD,” 23 met criteria for “Low VWF,” 14 were diagnosed with a “Platelet Function Defect,” and 2 children had bleeding secondary to Ehlers Danlos syndrome. Children with non-bleeding disorders (e.g. Factor XII deficiency) or no laboratory evidence of a bleeding disorder were classified as “No Bleeding Disorder.” In general, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and positive diagnostic likelihood ratio of the bleeding questionnaire demonstrated poor predictive value in our patient population with the exception of high specificity in ruling out “Definite Type 1 VWD” (Table). The NPV was comparably high with both qualitative (>2 bleeding symptoms) and quantitative (BS ≥2) criteria. CONCLUSIONS The Vicenza score, previously validated in adults and in a pediatric primary care setting, appears to have limited predictive value in a pediatric tertiary care setting when evaluating patients with platelet function defects or low VWF levels. While the Vicenza score has a high NPV to exclude “Definite Type 1 VWD,” the use of simpler qualitative criteria is similarly predictive. Disclosures No relevant conflicts of interest to declare.

scholarly journals Quantitative impact of using different criteria for the laboratory diagnosis of type 1 von Willebrand disease

2014 ◽  
Vol 12 (8) ◽  
pp. 1238-1243 ◽  
Author(s):  
T. Quiroga ◽  
M. Goycoolea ◽  
S. Belmont ◽  
O. Panes ◽  
E. Aranda ◽  
...  
Keyword(s):  
Laboratory Diagnosis ◽  
Von Willebrand Disease ◽  
Von Willebrand ◽  
Quantitative Impact

Von Willebrand Factor Collagen Binding Provides a Sensitive Screen for Identification of Type 2A and 2B Von Willebrand Disease

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 379-379
Author(s):  
Veronica H Flood ◽  
Joan Cox Gill ◽  
Kenneth D Friedman ◽  
Pamela A Christopherson ◽  
Paula M. Jacobi ◽  
...  
Keyword(s):  
Molecular Weight ◽  
High Molecular Weight ◽  
Von Willebrand Disease ◽  
Collagen Binding ◽  
The Mean ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Normal Controls ◽  
High Molecular Weight Multimers

Abstract Abstract 379FN2 Collagen binding is an easily performed test of von Willebrand factor (VWF) function but its role in clinical evaluation is still debated. Analysis of multimer distribution, on the other hand, is time-consuming and technically challenging. We hypothesized that VWF antigen (VWF:Ag), ristocetin cofactor activity (VWF:RCo), and collagen binding (VWF:CB) could identify the subset of von Willebrand disease (VWD) cases in which multimer analysis would be informative. Subjects from the Zimmerman Program for the Molecular and Clinical Biology of VWD were analyzed for VWF:Ag, VWF:RCo, VWF:CB (with type III human placental collagen), multimer distribution, and full VWF exon sequencing. Normal controls as well as patients with type 1, 2A, 2B, 2M, and 2N VWD were analyzed. The mean VWF:CB/VWF:Ag ratio for subjects with normal multimers was 1.10, while the mean ratio for subjects with abnormal multimers was 0.51 (p<0.001). When results were restricted to those subjects with confirmed type 2A or type 2B mutations, however, the mean ratio for subjects with abnormal multimers decreased to 0.41 (p<0.001 compared to those with normal multimers). For the 146 normal controls with multimer results available, 2 had absence of the highest molecular weight multimers, but normal collagen binding, normal bleeding scores, and no evidence of a VWF gene mutation, suggesting that the multimer results represented assay artifact. 354 type 1 subjects were examined; of those, 12 had abnormal multimer patterns. 7 had loss of the high molecular weight multimers. Of these, 5 had known type 1 VWD mutations and normal VWF:CB/VWF:Ag ratios, possibly representing sample artifacts rather than a true multimer abnormality, as no multimer issues have been previously reported for these mutations. One had no mutation found and one had a type 2A mutation. 2 had a full spectrum of multimers with relatively increased staining of the lower molecular weight bands; both with novel A1 domain mutations that are currently under investigation. 3 had larger than normal multimers observed, all with normal VWF:CB/VWF:Ag ratios. Of the 342 type 1 subjects with normal multimers, only one had a VWF:CB/VWF:Ag ratio of <0.7, likely due to very low values (VWF:CB of 2 and VWF:Ag of 4). There were 36 type 2A subjects available for analysis. 27 had loss of high molecular weight multimers. Only 3 of those had VWF:CB/VWF:Ag ratios >0.7, but none of those subjects had VWF mutations consistent with type 2A VWD. 7 subjects had a shift from high to low molecular weight multimers, 4 with VWF:CB/VWF:Ag ratios >0.7 and either known type 1 mutations or novel VWF gene mutations. 2 subjects had normal multimer distribution, one with a type1 VWD mutation and one with a novel mutation. Characterization of these novel mutations is in progress. All the 17 type 2B subjects had loss of high molecular weight multimers and abnormal collagen binding, with a VWF:CB/VWF:Ag ratio <0.7. Interestingly, however, not all had a reduced VWF:RCo/VWF:Ag ratio, suggesting VWF:CB would be required in addition to VWF:RCo if multimer distribution was omitted in initial evaluation of this type of VWD. Of 18 type 2M subjects, only one had an abnormal multimer distribution. That subject had no mutations in the VWF coding sequence and normal VWF:CB, although the VWF:RCo/VWF:Ag ratio was low at 0.53. Repeat analysis of a new sample from this subject is pending. All 7 type 2N VWD subjects had normal multimers and VWF:CB/VWF:Ag ratios >0.7. In our population, with the exception of mutations that are yet to be characterized, the combination of VWF:Ag, VWF:RCo and VWF:CB was sufficient to categorize patients as normal, type 1, type 2A, 2B or 2M in the before multimer analysis. These findings suggest that VWF:CB is a sensitive screen for detection of an abnormal multimer distribution. Collagen binding is technically much easier to perform, allowing multimer analysis to be reserved for those cases with low VWF:RCo/VWF:Ag or low VWF:CB/VWF:Ag ratios. Disclosures: No relevant conflicts of interest to declare.

Patterns of Bleeding in Males with Von Willebrand Disease

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1129-1129
Author(s):  
Manpreet K. Sandhu ◽  
Shailja Shah ◽  
Sari H Jacoby ◽  
Alice J. Cohen
Keyword(s):  
Family History ◽  
Positive Family History ◽  
Von Willebrand Disease ◽  
Bleeding Complications ◽  
Invasive Procedures ◽  
Dental Procedures ◽  
The Mean ◽  
Von Willebrand ◽  
Male Subjects

Abstract Abstract 1129 Background: Von Willebrand disease (vWD) is the most common inherited bleeding disorder in the United States, affecting about 1–2 % of the population. It is generally inherited as an autosomal dominant trait and is equally prevalent in males and females. Though this disorder usually manifests as mucosal bleeding, it is well known that there is a wide variation in clinical severity. The symptoms of vWD are usually more obvious in women because of menstruation and labor/delivery; and may be significantly under recognized in men. The pattern of bleeding and presentation at diagnosis in males has previously only been described in a small population of type 1 vWD patients (pts). Patients and Methods: We performed a retrospective chart review of active male pts with vWD receiving care at the Comprehensive Hemophilia Treatment Center. Clinical information such as age at diagnosis, initial symptom prompting the diagnosis and clinical bleeding history was obtained. Invasive procedures were reviewed for bleeding complications and relevant hematological intervention. Relevant laboratory data like PT, PTT, von Willebrand antigen (vWF:Ag), von Willebrand ristocetin cofactor (vWF:RCoF) and factor VIII activity (FVIII:C) was noted. Results: We identified a total of 140 male subjects with the diagnosis of vWD. Of the 140, 85 were evaluable with complete data. The mean age of the pts at the time of the study is 19 years (yrs) (1–79 yrs). 76/85 (89%) are type 1, 6/85 (7%) type 2 and 2/85 (4%) type 3 vWD. The mean age at diagnosis was 9.7 yrs (0.5–60 yrs) with 62/85 (73%) being diagnosed at age ≤ 10 yrs. The most common initial presentations leading to the diagnosis of vWD were epistaxis (25/85; 29%), a positive family history (24/85; 28%), prolonged preoperative (preop) PTT (14/85; 16%), easy bruising (10/85; 12%) and postoperative (postop) bleeding (5/85; 6%) pts. The mean lab values of vWF:Ag 48 IU/dl, vWF:RCoF 45 IU/dl and FVIII:C 62 IU/dl. 25/85 (29%) pts have one of the above parameters measuring < 30 IU/dl. Among those who ever experienced bleeding, the most common manifestations were epistaxis (30/85; 35%), easy bruising (10/85; 12%), postop bleeding (10/85; 8%), hemarthrosis (4/85; 5%), hematuria and oral bleeds (3/85; 4% each). A total of 48 surgical procedures occurred, consisting of 18 dental procedures, 13 tonsillectomy/adenoidectomy (T/A), 7 circumcisions, 5 joint surgeries, 2 port placements and 1 each of cystoscopy, orchiopexy and heart surgery. Bleeding complications were common 10/48 (21%): 5 with dental procedures, 2 each with T/A and circumcision and 1 with cystoscopy; all occurring in the absence of prophylactic treatment and 2/10 (20%) complications requiring transfusion of blood products. Conclusions: In our study which included types 1, 2 and 3 vWD pts, the majority of male subjects were symptomatic at the time of diagnosis, whereas about 40% were brought to attention due to a positive family history or an abnormal preop screening test. As opposed to previous reports, postop bleeding was a rare initial presentation in our larger cohort, possibly due to improved preop screening and earlier diagnosis. The most common pattern of bleeding amongst the symptomatic pts was mucosal, in the form of epistaxis and easy bruising. Bleeding complications can occur with invasive procedures, so aggressive use of DDAVP or clotting factor concentrates is warranted in a pt with known diagnosis of vWD. Disclosures: No relevant conflicts of interest to declare.

Spectrum of Type 2 Von Willebrand Disease in the Zimmerman Program

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 472-472 ◽  
Author(s):  
Veronica H Flood ◽  
Pamela A Christopherson ◽  
Daniel B Bellissimo ◽  
Joan Cox Gill ◽  
Sandra L Haberichter ◽  
...  
Keyword(s):  
Sequence Variation ◽  
Von Willebrand Disease ◽  
Sequence Variations ◽  
Platelet Binding ◽  
The Mean ◽  
Bleeding Score ◽  
Von Willebrand ◽  
Index Cases

Abstract While von Willebrand disease (VWD) is the most common inherited bleeding disorder, most patients have quantitative defects in von Willebrand factor (VWF). The qualitative variants, collectively termed type 2 VWD, are less common, but also in general more severe than type 1 VWD. However, despite a common laboratory phenotype of decreased VWF:RCo/VWF:Ag ratio for types 2A, 2B, and 2M VWD, the clinical phenotype is highly variable. We examined index cases and affected family members enrolled in the Zimmerman Program with a phenotypic diagnosis of type 2 VWD. All subjects had factor VIII (FVIII), VWF antigen (VWF:Ag), VWF ristocetin cofactor activity (VWF:RCo), and multimer distribution analyzed in a central laboratory. For calculation of mean VWF:RCo values, a level of 5 was assigned to subjects with VWF:RCo below the laboratory lower limit of detection of 10 IU/dL. A platelet binding assay was also performed using a gain of function GPIb containing 2 mutations that enable spontaneous binding to VWF in the absence of ristocetin (VWF:GPIbM). Full length VWF gene sequencing was performed for all index cases. Targeted sequencing was performed for family members to ascertain the presence or absence of sequence variations found in the index case. Bleeding symptoms were quantified using the ISTH bleeding assessment tool and reported as bleeding scores (BS). Mean FVIII, VWF:Ag, VWF:RCo, and BS are listed in the table below for each type 2 variant. For type 2A VWD, 113 subjects have been enrolled to date. All had an abnormal multimer distribution with loss of high molecular weight multimers. 6 type 2A subjects had a VWF:RCo/VWF:Ag ratio of ≤0.7. The lowest VWF:RCo levels were seen in the type 2A cohort with 60% <10. 98% of type 2A subjects had an identified sequence variation on full length sequencing. 25% had the p.R1597W sequence variation and an additional 4 subjects had p.R1597Q. The mean bleeding score for the subjects with sequence variations at 1597 was 10.6. 11% of subjects had p.R1374H, which correlated with a higher mean bleeding score of 12.4. Mean bleeding score for the remainder of the type 2A subjects was lower, at 6.6, suggesting that differences in VWF genetics may account for differences in phenotype, despite the common type 2A laboratory presentation of reduced VWF:RCo and loss of high molecular weight multimers. 44 type 2B subjects have been enrolled to date, all with abnormal multimer distribution and either documented abnormal VWF-platelet binding or a presence of a known type 2B sequence variation. Sequence variations were found in 100% of subjects. The most common sequence variations were p.V1316M (20%), p.R1306W (18%), p.R1341Q (11%), and p.H1268Y (9%). Mean VWF:RCo/VWF:Ag ratios ranged from 0.32-1.12, suggesting that a normal VWF:RCo/VWF:Ag ratio cannot completely exclude the possibility of type 2B VWD. Most (94%) had increased VWF:GPIbM. Subjects with p.V1316M and p.R1306W/Q sequence variations had lower VWF:RCo compared to subjects with p.R1341Q/W but mean bleeding scores did not differ. 59 type 2M subjects have been enrolled to date. Mean VWF:RCo/VWF:Ag ratio was 0.46 (range 0.14-0.7). Sequence variations were found in 93% of subjects. R1374C was found in 13 members from one family. While mean VWF levels were similar to the entire 2M group, a wide range in VWF:Ag and VWF:RCo/VWF:Ag ratio was observed, accompanied by a corresponding range in BS from 0-8. This suggests that other modifiers of phenotype may be present aside from the VWF sequence variation. 11 type 2N subjects have been enrolled to date, all with low VWF binding to FVIII. Sequence variations were found in 100% of this cohort. R854Q was present in 89% of subjects. Bleeding scores were highest for homozygous 2N sequence variations. Overall, the mean BS for type 1 VWD subjects was 6.3, the mean BS for type 2 VWD subjects was 7.5, and the mean BS for type 3 VWD subjects was 16.8. Types 2A and 2N had higher bleeding scores on average than type 2B, and type 2M subjects had on average the lowest bleeding scores. Although heterogeneity was seen across all the type 2 variants, both laboratory testing and genetic testing are useful in categorizing and phenotyping type 2 VWD. Table. FVIII (mean) VWF:Ag (mean) VWF:RCo (mean) BS (mean) Type 2A 47 34 12 8.7 Type 2B 45 36 23 7.1 Type 2M 62 54 21 5.4 Type 2N 30 69 76 8.3 Disclosures Montgomery: Immucor: Patents & Royalties.

Laboratory Diagnosis of von Willebrand Disease

2009 ◽  
Vol 03 (01) ◽  
pp. 33 ◽  
Author(s):  
Muriel Meiring ◽  
Philip N Badenhorst ◽  
Mareli Kelderman ◽  
◽  
◽  
...  
Keyword(s):  
Factor Viii ◽  
Correct Diagnosis ◽  
Laboratory Diagnosis ◽  
Binding Activity ◽  
Von Willebrand Disease ◽  
Coagulant Activity ◽  
Low Sensitivity ◽  
Von Willebrand ◽  
Willebrand Factor

von Willebrand disease (VWD) is a bleeding disorder caused by either quantitative (type 1 and 3) or qualitative (type 2) defects of von Willebrand factor (VWF). No single available test provides appropriate information about the various functions of VWF, and the laboratory diagnosis of VWD is based on a panel of tests, including the measurement of factor VIII coagulant activity (FVIIIC), VWF antigen levels (VWF:Ag), VWF activity as measured by the ristocetin co-factor activity (VWF:RCo), the collagen-binding activity of VWF (VWF:CB), VWF multimer analysis, ristocetininduced platelet agglutination (RIPA), the factor-VIII-binding assay of plasma VWF and VWF propeptide levels. Due to the heterogeneity of VWF defects and the variables that interfere with VWF levels, a correct diagnosis of types and subtypes may sometimes be difficult, but is very important for therapy. Furthermore, the RCo assay and the RIPA test are based on platelet agglutination in reaction with the non-physiological antibiotic ristocetin. These tests also have low sensitivity and are difficult to standardise. Therefore, several analyses (tests) are required to diagnose VWD and it is important to be aware of the pitfalls to which these tests are subjected in terms of the diagnosis. In this article, the laboratory diagnosis of patients with type 1, 2A, 2B, 2M, 2N and 3 VWD will be explained by using a modified algorithm that was first proposed by the guidelines for diagnosis and treatment of VWD in Italy.

Laboratory diagnosis of von Willebrand disease

2010 ◽  
Vol 30 (04) ◽  
pp. 203-206 ◽  
Author(s):  
R. Schneppenheim ◽  
J. Patzke
Keyword(s):  
Laboratory Diagnosis ◽  
Binding Activity ◽  
Von Willebrand Disease ◽  
Activity Assay ◽  
Binding Assays ◽  
New Type ◽  
Von Willebrand ◽  
Made In

SummaryOver the last decade, considerable progress has been made in the laboratory diagnosis of VWD. Precise, sensitive and automated VWF : Ag assays became widely available. The VWF : RCo performance was improved to a certain degree. However, the sensitivity, precision and general availability of automated applications is not yet optimal. Nevertheless, this type of assay is still recognized as superior to other activity assays, e. g. VWF : CBA assays and antibody-binding “activity” assays, for the detection of defects in VWF function.A decision limit of either 30 or 40 IU dl-1 VWF (VWF:RCo or VWF:Ag) is recommended for a diagnosis of type 1 VWD. Type 2 VWD can be differentiated from type 1 by calculating the VWF:RCo/VWF:Ag ratio.Improved and easier to perform multimer analysis and genetic testing are beginning to facilitate the diagnosis of the VWD type 1, 2A, 2B, 2N, 2M or 3. Within type 1 or 2, a decreased VWF survival can be detected by the VWFpp assay and its ratio to VWF : Ag.A new type of VWF activity assay, based on the binding of VWF to a GPIb〈-fragment, has been developed. One assay variant does not need ristocetin as a cofactor anymore. The performance investigations presented so far are very promising. It is probable that these GPIb〈-binding assays will detect functional VWF defects as the VWF : RCo assay, but are much more sensitive and precise. Fully automated applications on routine analyzers are expected to be commercialized soon.

scholarly journals New advances in the diagnosis of von Willebrand disease

Hematology ◽  
2019 ◽  
Vol 2019 (1) ◽  
pp. 596-600
Author(s):  
Ruchika Sharma ◽  
Sandra L. Haberichter
Keyword(s):  
Diagnostic Algorithm ◽  
Laboratory Diagnosis ◽  
Binding Activity ◽  
Von Willebrand Disease ◽  
Assessment Tools ◽  
Molecular Testing ◽  
Platelet Binding ◽  
History Of ◽  
Von Willebrand

Abstract von Willebrand disease (VWD) is the most common autosomal inherited bleeding disorder, with an estimated prevalence of 1 in 1000 individuals. VWD is classified into quantitative and qualitative forms. Diagnosis of VWD is complex and requires (1) a personal history of bleeding symptoms, (2) family history of bleeding or VWD, and (3) confirmatory laboratory testing. There are certain bleeding assessment tools to objectively measure bleeding symptoms in patients that have been shown to correlate with the diagnosis as well as the severity of VWD. Laboratory diagnosis requires at least initially a measurement of von Willebrand factor (VWF) antigen levels, VWF platelet binding activity (VWF:RCo, VWF:GPIbM, and VWF:GPIbR), and factor VIII (FVIII) activity. Additional testing to confirm the specific subtype may include VWF collagen binding activity, low-dose ristocetin VWF-platelet binding, FVIII-VWF binding, VWF multimer analysis, and VWF propeptide antigen. Recent advances have been made regarding some of these assays. Molecular testing in VWD is not found to be useful in “low VWF” or most type 1 VWD cases but may be informative in patients with severe type 1 VWD, type 1C VWD, type 2 VWD, or type 3 VWD for accurate diagnosis, genetic counseling, and appropriate treatment. The diagnostic algorithm for VWD is complex, but advances continue to be made in improving VWF functional assays and diagnostic pathways.

scholarly journals Outgrowing the laboratory diagnosis of type 1 von Willebrand disease: A two decade study

2017 ◽  
Vol 93 (2) ◽  
pp. 232-237 ◽  
Author(s):  
Mouhamed Yazan Abou-Ismail ◽  
Gbolahan O. Ogunbayo ◽  
Michelle Secic ◽  
Peter A. Kouides
Keyword(s):  
Laboratory Diagnosis ◽  
Von Willebrand Disease ◽  
Von Willebrand
Sign in / Sign up

Export Citation Format

Share Document