von Willebrand Factor Propeptide to Antigen Ratio in HIV Infected Pregnancy: Evidence of Endothelial Activation

2021 ◽  
Author(s):  
Elise Schapkaitz ◽  
Elena Libhaber ◽  
Barry F Jacobson ◽  
Muriel Meiring ◽  
Harry R Büller
Keyword(s):  
Von Willebrand Factor ◽  
Endothelial Activation ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Von Willebrand Factor Propeptide

scholarly journals Insights Into Immunothrombosis: The Interplay Among Neutrophil Extracellular Trap, von Willebrand Factor, and ADAMTS13

2020 ◽  
Vol 11 ◽  
Author(s):  
Junxian Yang ◽  
Zhiwei Wu ◽  
Quan Long ◽  
Jiaqi Huang ◽  
Tiantian Hong ◽  
...  
Keyword(s):  
Von Willebrand Factor ◽  
Therapeutic Strategy ◽  
Endothelial Activation ◽  
Endothelial Damage ◽  
Neutrophil Extracellular Trap ◽  
Activated Neutrophils ◽  
A Disintegrin And Metalloproteinase ◽  
Von Willebrand ◽  
Willebrand Factor

Both neutrophil extracellular traps (NETs) and von Willebrand factor (VWF) are essential for thrombosis and inflammation. During these processes, a complex series of events, including endothelial activation, NET formation, VWF secretion, and blood cell adhesion, aggregation and activation, occurs in an ordered manner in the vasculature. The adhesive activity of VWF multimers is regulated by a specific metalloprotease ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motifs, member 13). Increasing evidence indicates that the interaction between NETs and VWF contributes to arterial and venous thrombosis as well as inflammation. Furthermore, contents released from activated neutrophils or NETs induce the reduction of ADAMTS13 activity, which may occur in both thrombotic microangiopathies (TMAs) and acute ischemic stroke (AIS). Recently, NET is considered as a driver of endothelial damage and immunothrombosis in COVID-19. In addition, the levels of VWF and ADAMTS13 can predict the mortality of COVID-19. In this review, we summarize the biological characteristics and interactions of NETs, VWF, and ADAMTS13, and discuss their roles in TMAs, AIS, and COVID-19. Targeting the NET-VWF axis may be a novel therapeutic strategy for inflammation-associated TMAs, AIS, and COVID-19.

Changes in ADAMTS 13 Activity and Von Willebrand Factor Parameters during Acute Dengue Infection.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1492-1492
Author(s):  
Darintr Sosothikul ◽  
Panya Seksarn ◽  
Sureeporn Pongsawaluk ◽  
Jeanne M. Lusher
Keyword(s):  
Von Willebrand Factor ◽  
Cell Activation ◽  
Dengue Infection ◽  
Plasma Concentrations ◽  
Endothelial Activation ◽  
Healthy Children ◽  
Endothelial Cell Activation ◽  
Convalescent Phase ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract Dengue virus causes febrile illnesses: Dengue Fever (DF) and less frequently a life-threatening illness, Dengue Hemorrhagic Fever (DHF). The pathophysiology of hemostatic defect in dengue infection is thought to relate to the direct effect of virus or cytokines on endothelial activation. To study the state of endothelial activation during dengue infection, we measured plasma levels of von Willebrand factor antigen (vWF:Ag), vWF-collagen binding assay (vWF:CBA), and ADAMTS 13 activity in 42 children (20 with DF and 22 with DHF) during 3 phases of illness: febrile, toxic, and convalescent phase. 38 healthy children comprised as controls. Our data shows that both VWF:Ag and vWF:CBA levels were significantly higher in dengue patients (p ≤ 0.001 in both DF and DHF patients) versus controls. DHF patients had significantly higher of VWF: Ag (p = 0.01, versus DF). ADAMTS 13 activity levels were significantly decreased only in DHF patients during 3 phases of the illness (febrile; mean 78%; p = 0.016, toxic; mean 68%; p<0.001 and convalescent; mean 69%; p<0.001 compared to mean 104% of the controls). Compared to DF patients, DHF patients had significantly lower plasma concentrations of ADAMTS 13 activity during the febrile, toxic and convalescent phase (p = 0.039, p = 0.002 and p =0.003, respectively). Endothelial cell activation is a hallmark of dengue infection especially in DHF patients; indicated by a significant rise in VWF:Ag and vWF:CBA and a reciprocal decline in ADAMTS 13 activity.

The role of the D1 domain of the von Willebrand factor propeptide in multimerization of VWF

Blood ◽  
2002 ◽  
Vol 100 (5) ◽  
pp. 1699-1706 ◽  
Author(s):  
Jonathan B. Rosenberg ◽  
Sandra L. Haberichter ◽  
Mary A. Jozwiak ◽  
Elizabeth A. Vokac ◽  
Philip A. Kroner ◽  
...  
Keyword(s):  
Von Willebrand Factor ◽  
Tertiary Structure ◽  
Genomic Analysis ◽  
Wild Type ◽  
Binding Factor ◽  
Platelet Binding ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Von Willebrand Factor Propeptide

While studying patient plasma containing an unusual pattern of von Willebrand factor (VWF) multimers, we discovered a previously unreported phenomenon: heavy predominance of dimeric VWF. Genomic analysis revealed a new congenital mutation (Tyr87Ser) that altered the final stages of VWF biosynthesis. This mutation in the propeptide (VWFpp) resulted in synthesis of dimeric VWF with an almost complete loss of N-terminal multimerization. The multimer pattern in patient plasma appears to result from separate alleles' synthesizing wild-type or mutant (dimeric) VWF, with homodimers composing the predominant protomeric species. We have expressed VWF protein containing the Tyr87Ser mutation and analyzed the intracellular processing and resulting VWF biological functions. The expressed dimeric VWF displayed a loss of several specific functions: collagen binding, factor VIII binding, and ristocetin-induced platelet binding. However, granular storage of dimeric VWF was normal, demonstrating that the lack of multimerization does not preclude granular storage. Although the tertiary structure of the VWFpp remains unknown, the mutant amino acid is located in a region that is highly conserved across several species and may play a major role in the multimerization of VWF. Our data suggest that one function of the highly cysteine-rich VWFpp is to align the adjacent subunits of VWF into the correct configuration, serving as an intramolecular chaperone. The integrity of the VWFpp is essential to maintain the proper spacing and alignment of the multiple cysteines in the VWFpp and N-terminus of the mature VWF.

scholarly journals von Willebrand factor propeptide: biology and clinical utility

Blood ◽  
2015 ◽  
Vol 126 (15) ◽  
pp. 1753-1761 ◽  
Author(s):  
Sandra L. Haberichter
Keyword(s):  
Von Willebrand Factor ◽  
Clinical Utility ◽  
Coagulation Factor ◽  
Von Willebrand Disease ◽  
True Type ◽  
And Function ◽  
Type 3 ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Von Willebrand Factor Propeptide

Abstract von Willebrand factor (VWF) is a large multimeric glycoprotein that mediates the attachment of platelets to damaged endothelium and also serves as the carrier protein for coagulation factor VIII (FVIII), protecting it from proteolytic degradation. Quantitative or qualitative defects in VWF result in von Willebrand disease (VWD), a common inherited bleeding disorder. VWF is synthesized with a very large propeptide (VWFpp) that is critical for intracellular processing of VWF. VWFpp actively participates in the process of VWF multimerization and is essential for trafficking of VWF to the regulated storage pathway. Mutations identified within VWFpp in VWD patients are associated with altered VWF structure and function. The assay of plasma VWFpp has clinical utility in assessing acute and chronic vascular perturbation associated with diseases such as thrombotic thrombocytopenic purpura, sepsis, and diabetes among others. VWFpp assay also has clear utility in the diagnosis of VWD subtypes, particularly in discriminating true type 3 subjects from type 1C (reduced plasma survival of VWF), which is clinically important and has implications for therapeutic treatment.

scholarly journals Elevated plasma von Willebrand factor levels are associated with subsequent ischemic stroke in persons with treated HIV infection

2021 ◽  
Author(s):  
Susan M Graham ◽  
Robin M Nance ◽  
Junmei Chen ◽  
Jennie Le ◽  
Dominic W Chung ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Viral Load ◽  
Hiv Infection ◽  
Von Willebrand Factor ◽  
Endothelial Activation ◽  
Apolipoprotein A1 ◽  
Soluble Cd14 ◽  
Amyloid A ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract Background We assessed whether key biomarkers of endothelial activation and hemostasis/thrombosis were elevated in individuals receiving effective antiretroviral therapy (ART) in the year before ischemic stroke. Methods We conducted a case-control study nested in the CNICS cohort, comparing 42 adjudicated cases with ischemic stroke to 83 controls matched for ART regimen. Angiopoietin-1, angiopoietin-2, C-reactive protein, interleukin-6, plasminogen activation inhibitor-1, P-selectin, serum amyloid-A, soluble CD14, ICAM-1, VCAM-1, apolipoprotein A1, ADAMTS13, and von Willebrand factor (VWF) were measured in stored plasma collected before the stroke event. We used conditional logistic regression to identify associations with ischemic stroke, with and without adjustment for Atherosclerotic Cardiovascular Disease (ASCVD) and Veterans Aging Cohort Study (VACS) scores. Results After adjustment for age and sex, higher plasma viral load and higher angiopoeitin-2, soluble CD14, and VWF were associated with increased odds of ischemic stroke; higher nadir CD4 count was associated with decreased odds of ischemic stroke. VWF remained associated with subsequent ischemic stroke after adjustment for ASCVD score (adjusted odds 1.74, 95%CI 1.01–2.98 per log2 increment). In a separate model adjusting for VACS score, only VWF (adjusted odds 1.80, 95% CI 1.04–3.12 per log2 increment) was associated with subsequent ischemic stroke. In a sensitivity analysis excluding participants with viral load ≥400 copies/mL, associations between VWF and ischemic stroke were attenuated, with risk estimates ranging from 1.59–1.64 per log2 increment. Conclusions Endothelial activation and related release and attachment of VWF may play an important role in ischemic stroke among persons living with treated HIV infection.

Verification of a rapid von Willebrand factor propeptide assay

2020 ◽  
pp. 78-82
Author(s):  
R Maleka ◽  
M Meiring
Keyword(s):  
Von Willebrand Factor ◽  
World Health ◽  
Enzyme Linked Immunosorbent Assay ◽  
Rapid Assay ◽  
Commercial Assay ◽  
Two Samples ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Von Willebrand Factor Propeptide

Background: Von Willebrand disease (VWD) is the most common inherited bleeding disorder caused by a deficiency or defect in von Willebrand factor (VWF). Quantitative defects include, type 1 VWD and type 3 VWD. Type 1 VWD is either due to decreased synthesis and secretion, or increased clearance of VWF. It is essential to diagnose individuals with increased VWF clearance, as treatment of these patients with 1-deamino-8-D-arginine vasopressin is not effective. Currently, there is one commercial assay that measures von Willebrand factor propeptide (VWFpp) levels. This assay is time consuming to perform. With this research we developed and verified a rapid assay to determine VWFpp levels in patient plasma. Methods: The commercial VWF mouse anti-human VWF propeptide matched antibody pair (clones CLB-Pro 35 and CLB-Pro 14.3) was used in enzyme-linked immunosorbent assays of the commercial and the rapid method. While the CLB-Pro commercial assay uses two-hour incubations, our rapid assay uses 30 minute incubations. We compared our assay to the CLB-Pro commercial assay using twenty type 1 VWD patient plasma. Two samples, the World Health Organization (WHO) 6th International Standard (IS) for factor VIII (FVIII)/VWF and a type 1 VWD patient with increased clearance were also tested four times in duplicate for five consecutive days to determine the inter- and intra-assay precision. Results: Our rapid assay showed equal sensitivity to the CLB-Pro commercial assay by detecting 1.5625% VWFpp. The intra- and interassay CVs of our assay were acceptable according to the Food and Drug Administration guideline of 2018. Conclusion: This rapid enzyme-linked immunosorbent assay (ELISA) is as sensitive and precise as the CLB-Pro commercial assay. Therefore, it can be used to rapidly diagnose patients with increased VWF clearance.

scholarly journals Acquired von Willebrand syndrome: von Willebrand factor propeptide to von Willebrand factor antigen ratio predicts remission status

Blood ◽  
2014 ◽  
Vol 124 (5) ◽  
pp. e1-e3 ◽  
Author(s):  
Adrienne Lee ◽  
Gary Sinclair ◽  
Karen Valentine ◽  
Paula James ◽  
Man-Chiu Poon
Keyword(s):  
Von Willebrand Factor ◽  
Acquired Von Willebrand Syndrome ◽  
Remission Status ◽  
Von Willebrand Factor Antigen ◽  
Key Points ◽  
Relapsing Remitting ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Factor Antigen ◽  
Von Willebrand Factor Propeptide

Key Points Remission status in relapsing-remitting AVWS depends on the balance of VWF clearance by anti-VWF antibody and VWF secretion. VWFpp:Ag ratio is a simple assay that provides information on this balance and predicts remission status in this case of AVWS.

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