Multimer Analysis of Von Willebrand Factor in Von Willebrand Disease with a Hydrasys Semi-Automatic Analyzer—Single-Center Experience

Škorňová, Ingrid; Šimurda, Tomáš; Staško, Ján; Žolková, Jana; Sokol, Juraj; Holly, Pavol; Dobrotová, Miroslava; Plamenova, Ivana; Hudeček, Jan; Brunclíková, Monika; Stryckova, Alena; Kubisz, Peter

doi:10.3390/diagnostics11112153

Cited by 9 publications

(6 citation statements)

References 33 publications

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“…Astonishingly, vWF antigen and activity were within normal ranges, but the FVIII level was repeatedly between 4 and 5.5%. Extended quantitative and qualitative evaluations of vWF multimers were not performed; they could have given helpful information for the exclusion of vWD type 2 [ 17 ]. The genetic testing revealed a pathogenic hemizygous F8: c.6977 G>A variant, identified in exon 26 of the F8 gene (ref seq NM_000132.3).…”

Section: Resultsmentioning

confidence: 99%

Challenges in the Diagnosis and Management of Non-Severe Hemophilia

Boeriu

Arghirescu

Şerban

et al. 2022

JCM

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(1) Background: Mild and moderate hemophilia, synonymous with non-severe hemophilia (NSH), are of constant interest for the clinicians. Bleeding occurs usually after trauma, injury, surgery, or inhibitor development, sometimes leading to a shift of the clinical phenotype from mild to severe, even with life-threatening and unexpected outcomes. (2) Methods: We performed a retrospective observational study conducted on 112 persons with congenital coagulopathies, 26 of them with NSH, admitted to our clinic in the period 2000 to 2022. For the diagnosis, we used laboratory studies (complete blood cell count, coagulation assays, biochemistry, thromboelastography, genetic tests) and imaging investigations (X-ray, ultrasound, CT, MRI). We selected four cases confronted with pitfalls of diagnosis and evolution in order to illustrate the sometimes provocative field of NSH. (3) Results: Confronted with challenging cases with under-, missed or delayed diagnosis and severe consequences, we aimed at presenting four such selected cases with mild or moderate hemophilia, real pitfalls in our clinical activity. (4) Conclusions: In the field of NSH, if not timely recognized, tending sometimes to remain ignored by caregivers and patients themselves, we can be confronted with challenging diagnostic situations and life-threatening bleeds.

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Section: Resultsmentioning

confidence: 99%

Challenges in the Diagnosis and Management of Non-Severe Hemophilia

Boeriu

Arghirescu

Şerban

et al. 2022

JCM

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“…It is known that non-O blood type individuals have higher (approximately 25%) FVIII:C and VWF:Ag than O blood type individuals [ 23 , 24 ]. A recently published single-centre study found that individuals with blood group O had approximately 10–20% lower plasma VWF levels compared to individuals without blood group O [ 25 ]. It has been suggested that the lower VWF:Ag in O blood type individuals is attributable to the susceptibility of VWF to ADAMTS13 proteolysis and the significantly increased hepatic clearance of VWF, which is mediated via the asialoglycoprotein receptor.…”

Section: Discussionmentioning

confidence: 99%

Clinical Application of Factor VIII:C to VWF:Ag Ratio for the Screening of Haemophilia A Carriers

Yoo

Jung

Choi

et al. 2022

JCM

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Analyses of factor VIII procoagulant activity (FVIII:C) and the FVIII:C to VWF:Ag ratio (FVIII:C/VWF:Ag ratio) have been investigated as screening bioassays to detect haemophilia carriers. This study aimed to determine the validity of the FVIII:C/VWF:Ag ratio and FVIII:C analyses as screening tests. We reviewed the medical records of 137 genetically confirmed, proband haemophilia A patients and 179 of their familial females who had undergone carrier testing. The collected data included the severity and mutation type of F8 gene from probands and age, ABO blood type, FVIII:C, VWF:Ag, and the result of targeted gene analysis in females. We diagnosed 110 females as carriers, and their FVIII:C and FVIII:C/VWF:Ag ratio were lower than those in 69 non-carriers (FVIII:C: 59.3 IU/dL vs. 106.1 IU/dL, p = 0.000; FVIII:C/VWF:Ag ratio: 0.62 vs. 1.08, p = 0.000). In receiver operating characteristic analysis, the areas under the curve (AUC) of the FVIII:C/VWF:Ag ratio and FVIII:C were 0.936 and 0.876, respectively. The cut-off value of FVIII:C/VWF:Ag ratio (0.81) at the maximum Youden J index provided a sensitivity of 82.8% and specificity of 96.6%. The cut-off value of FVIII:C (83.8 IU/dL) showed a sensitivity of 81.8% and specificity of 79.7%. Considering the AUC, the FVIII:C/VWF:Ag ratio is a good screening test to detect haemophilia A carriers, as evidenced by its specificity of 96.6%; however, it may also induce false-negative results.

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“…Other activities of VWF, such as its binding to collagen, were unaffected by polyP [13]. The multimerization state of VWF, which is decisive for some of its adhesion activities [16,17], also did not change in VWF incubated with polyP or polyP-degrading enzymes [13].…”

Section: Introductionmentioning

confidence: 91%

Polyphosphate Activates von Willebrand Factor Interaction with Glycoprotein Ib in the Absence of Factor VIII In Vitro

Montilla

Atienza-Navarro

García-Cozar

et al. 2022

IJMS

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Polyphosphate (polyP), a phosphate polymer released by activated platelets, may modulate various stages of hemostasis by binding to blood proteins. In this context, we previously reported that polyP binds to the von Willebrand factor (VWF). One of the most significant functions of VWF is to bind to and protect the blood circulating Factor VIII (FVIII). Therefore, here, we study the role of polyP in the VWF–FVIII complex in vitro and suggest its biological significance. Surface plasmon resonance and electrophoretic mobility assays indicated that polyP binds dynamically to VWF only in the absence of FVIII. Using the VWF Ristocetin Cofactor assay, the most accepted method for studying VWF in platelet adhesion, we found that polyP activates this role of VWF only at low levels of FVIII, such as in plasmas with chemically depleted FVIII and plasmas from severe hemophilia A patients. Moreover, we demonstrated that FVIII competes with polyP in the activation of VWF. Finally, polyP also increases the binding of VWF to platelets in samples from patients with type 2 and type 3 von Willebrand disease. We propose that polyP may be used in designing new therapies to activate VWF when FVIII cannot be used.

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Multimer Analysis of Von Willebrand Factor in Von Willebrand Disease with a Hydrasys Semi-Automatic Analyzer—Single-Center Experience

Cited by 9 publications

References 33 publications

Challenges in the Diagnosis and Management of Non-Severe Hemophilia

Challenges in the Diagnosis and Management of Non-Severe Hemophilia

Clinical Application of Factor VIII:C to VWF:Ag Ratio for the Screening of Haemophilia A Carriers

Polyphosphate Activates von Willebrand Factor Interaction with Glycoprotein Ib in the Absence of Factor VIII In Vitro

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