VWF is initially synthesised as a series of very large multimers that are degraded by the metalloprotease ADAMTS13 (A Disintegrin-like And Metalloprotease domain with Thrombospondin type I motifs).
The gene for VWF spans approximately 172kb of genomic sequence, consists of 52 exons, maps to chromosome 12 [12p13.3] and encodes a protein of 2813 amino acids that includes a signal peptide of 22 amino acids, a prepropeptide of 741 amino acids [residues 23-763] and a mature protein of 2050 amino acids [residues 764-2800]. A functional assay of plasma VWF that uses a monoclonal antibody that targets the part of the VWF molecule that binds to the GpIb receptor. Establishing the presence of any significant family history suggestive of a bleeding disorder. These can be of value in the identification of 2N VWD although this is not a widely available test and VWF gene analysis can be equally useful. VWF multimer analysis is a qualitative assay that depicts the variable concentrations of the different sized VWF multimers present in plasma.
VWF:Activity refers to a functional assay of plasma VWF that uses a monoclonal antibody that targets the part of the VWF molecule that binds to the GpIb receptor. FVIII:C is a measure of the cofactor function of the clotting factor VIII usually measured in a 1-stage functional assay. This is useful in studying patients with Type 1 VWD and in separating Type 1 patients with a normal VWF half-life from those with a shortened half-life e.g.
Screening for VWF inhibitors by means of a conventional inhibition assay [a mix of normal and test plasma and then assaying VWF levels] is very difficult .
The history can be very important in such cases as there is frequently no history suggestive of a bleeding disorder until very recently. Setting a goal, identifying the right patients, and implementing team care can help bring hypertension under control.Arnold E. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report.


2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). Call to action on use and reimbursement for home blood pressure monitoring: a joint scientific statement from the American Heart Association, American Society of Hypertension, and Preventive Cardiovascular Nurses Association. A deficiency of ADAMTS13 leads to the accumulation of ultra high molecular weight VWF multimers and the clinical and laboratory features of thrombotic thrombocytopenic purpura (TTP).
The mature protein is divided into a series of domains that contain the various functional domains - see Reference 1. Plasma VWF levels vary with blood group - individuals with blood group O have lower VWF levels than individuals of other blood groups. The bleeding history is fundamental to the diagnosis of VWD - the use of a formalised bleeding score is recommended - see references.
Type 1C VWD [Type 1 Vicenza] is a subtype of VWD due to mutation that gives to a VWF molecule with a short T½. Type 2 VWD is now subdivided into Type 2A1 due to abnormal VWF synthesis and Type 2A2 due to increased proteolysis by ADAMTS13. The discriminant power of bleeding history for the diagnosis of type 1 von Willebrand disease: an international, multicenter study. Evaluation of the diagnostic utility for von Willebrand disease of a pediatric bleeding questionnaire. Diagnosis and classification of von Willebrand disease: a review of the differential utility of various functional von Willebrand factor assays.
A person viewing it online may make one printout of the material and may use that printout only for his or her personal, non-commercial reference. The mature VWF protein found in the plasma has a half-life of approximately 12 hours (range 9–15 hours).


ELISA assays have been published for looking for VWF inhibitors but again do not always identify antibodies.
This becomes important in making a diagnosis of VWD when an individual has borderline VWF assays and is Blood Group O.
The diagnosis of von Willebrand disease: a guideline from the UK Haemophilia Centre Doctors' Organization. The molecular analysis of von Willebrand disease: a guideline from the UK Haemophilia Centre Doctors' Organisation Haemophilia Genetics Laboratory Network. A quantitative analysis of bleeding symptoms in type 1 von Willebrand disease: results from a multicenter European study (MCMDM-1 VWD). It costs an estimated $46 billion each year to address issues related to hypertension such as health care services, medications, and missed work. Consider follow-up labs when up-titrating or adding lisinopril, hydrochlorothiazide, or losartan.
This material may not otherwise be downloaded, copied, printed, stored, transmitted or reproduced in any medium, whether now known or later invented, except as authorized in writing by the AAFP.
Seven to eight out of every 10 people have their first heart attack or stroke or develop congestive heart failure because of uncontrolled blood pressure.1 It is clear that blood pressure control is essential to preventing multiple medical conditions from occurring or worsening.



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Comments

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